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This is regulated by both the specific subcellular localization and the timed expression and degradation of various cyclins and Cdk inhibitors throughout the cell cycle stomach pain treatment home purchase 2 mg tizanidine with amex. In general, the peak nuclear expression of a specific cyclin occurs at or just prior to the peak activity of the partner kinase, and following activation, the respective cyclins are degraded rapidly by the ubiquitin-mediated proteosomal pathway. In most cells, cyclin D-Cdk complexes are activated by mitogenic stimuli early in G1 followed by activation of cyclin E Cdk2 in mid G1 phase. Cyclin A-Cdk2 activation in late G1 phase follows cyclin E-Cdk activation and is essential for initiation of and progression though S phase and for the onset of mitosis. In mammalian cells, two B-type cyclins (cyclin B1 and cyclin B2) associate with Cdk1 to regulate entry into and exit from mitosis. One of the important substrates of the cyclin-D?, cyclin-E?, and cyclin-A?associated kinases is the retinoblastoma protein, pRb. In early G1 phase, pRb is hypophosphorylated and bound to a member of the E2F family of transcription factors. However, activation of cyclin D and later cyclin-E? dependent kinases during progression from G1 to S phase leads to the accumulation of pRb in a hyperphosphorylated state. The phosphorylation of the retinoblastoma protein is one indicator of cell cycle progression through the restriction point. The retinoblastoma protein is dephosphorylated in mitosis, prior to G1 phase of the next cell cycle. The four members, p15, p16, p18, and p19 are structurally related and act to destabilize the association of the D-type cyclins with Cdk4 or Cdk6. The p16 protein plays an important role in the proliferative arrest of cells at senescence and the p16 gene is frequently deleted in human cancers. Studies in 71 mice have suggested that this protein plays a tumour suppressor role since cell lines derived from p16-null mice undergo spontaneous immortalization with high frequency. Patients with several of these syndromes show marked chromosomal instability and predisposition to malignancy. Spontaneous 4 5 oxidative damage is known to occur in cells, producing 10 to 10 oxidative residues. If a cell cannot repair this continual onslaught of base damage, malignant transformation may occur. Nonhomologous end joining is error-prone and operates predominantly to repair damage in somatic cells during the G1 phase of the cell cycle. This early event precedes the actions of repair enzymes involved in homologous recombination and nonhomologous end-joining of these breaks. Tumour growth In normal tissues that undergo cell renewal, there is a balance between cell proliferation, growth arrest and differentiation, and loss of mature cells by programmed cell death or apoptosis. Tumours grow because the homeostatic mechanisms that maintain the appropriate number of cells in normal tissues are defective, leading to imbalance between cell proliferation and cell death, so that there is expansion of the cell population. However, the proliferative rate of tumour cells varies widely between tumours, nonproliferating cells are common, and there is often a high rate of cell death. Tumour growth: Tumour growth can be determined by estimating tumour volume as a function of time. Exponential growth will occur if the rates of cell production and of cell loss 75 or death are proportional to the number of cells present in the population. Exponential growth implies that the time taken for a tumour to double its volume is constant and may leads to the false impression that the rate of tumour growth is accelerating with time. Both require three volume doublings and during exponential growth they will occur over the same period of time. Estimates of the growth rates of untreated human tumours are limited but there are published estimates of the growth rate of many human tumours. In general these estimates indicate that there is a wide variation in growth rate, even among tumours of the same histologic type and site of origin. There is a tendency for childhood tumours and adult tumours that are known to be responsive to chemotherapy. Representative mean doubling times for lung metastases of common tumours in humans are in the range of 2 to 3 months. Tumours are unlikely to be detected until they grow to about 1 gram, and tumours of this size 9 will contain about one billion (10) cells. There is indirect evidence that many tumours arise 9 from a single cell, and a tumour containing about 10 cells will have undergone approximately thirty doublings in volume prior to clinical detection (because of cell loss, this will involve more than thirty consecutive divisions of the initial cell). After ten further doublings in 12 volume, the tumour would weigh about 1 kilogram (10 cells), a size that may be lethal to the host. Thus, the range of size over which the growth of a tumour may be studied represents a rather short and late part of its total growth history. Thus, early clinical detection may be expected to reduce but not to prevent the subsequent appearance of metastases. The proportion of thymidine labeled cells at a short interval after administration of tritiated thymidine (the labeling index) is a measure of the proportion of cells in S phase. Typical values for the proportion of cells in S phase are in the range of 3 to 15 percent for many types of human solid tumours. Higher rates of cell proliferation are evident in faster-growing malignancies, including acute leukemia and some lymphomas. However, the rate of cell proliferation is usually less than that of some cells in normal renewing tissues, such as the intestine or bone marrow. Thus, accumulation of cells in tumours is not due simply to an increased rate of cell proliferation as compared to the normal tissue of origin. Rather, there is defective maturation and the population of malignant cells increases because the rate of cell production exceeds the rate of cell death or removal from the population. Most tumours contain nonproliferating cells, and the term growth fraction describes the proportion of cells in the tumour population that is proliferating. The occurrence of extensive necrosis in solid tumours and of apoptotic cells and the ability of tumour cells to metastasize from a primary tumour indicate that there is considerable cell death or loss from many tumours. The rate of cell loss from tumours can be estimated by 76 comparing the rate of cell production (from assessment of the labeling index or fraction of S phase cells by flow cytometry) with the rate of tumour growth. The overall rate of cell production may be characterized by the potential doubling time of the tumour (Tpot), which is the expected doubling time of the tumour in the absence of cell loss. Flow cytometry: Flow cytometry is a method that allows the separation and sorting of cells based on cellular fluorescence. Flow cytometry can be used to estimate cell cycle phase distribution, growth fraction, and kinetic properties of cell populations. Several methods allow proliferating and nonproliferating cells to be distinguished by flow cytometry. The Ki-67 antigen has been used most often as a marker for proliferating cells although its function remains poorly understood. The mean values of Tpot are also much lower than estimates of volume doubling time for common human tumours (typically 2 to 3 months) because the rate of cell loss in many human tumours is in the range of 75 to 90 percent of the rate of cell production. Not surprisingly, well nourished cells close to blood vessels have a more rapid rate of cell proliferation than poorly nourished cells close to a region of necrosis. Slowly proliferating cells at a distance from functional blood vessels may be resistant to radiation because of hypoxia and to cytotoxic chemotherapeutic drugs because of their low proliferative rate and limited drug access. Initial evidence accrued from analysis of X-linked genes or gene products in cells from tumours in women who are heterozygous at these genetic loci. One of the X chromosomes becomes inactivated at random in all cells of females during early life. The normal tissues of heterozygous females are therefore mosaics that contain approximately equal number of cells in which one or the other (but not both) of the two alleles of a gene on the X chromosomes are expressed. However, cells in tumours arising in such individuals usually express only one allele of such genes?for example they express only one form (isoenzyme) of the X-linked glucose-6-phosphate dehydrogenase. Other clonal markers include chromosomal rearrangements such as the Philadelphia chromosome in chronic myelogenous leukemia; uniquely rearranged immunoglobulins or T-cell receptors expressed by B-cell lymphomas or multiple myelomas and T-cell lymphomas; and molecular markers whose detection has been facilitated by the availability of gene sequencing. The above techniques have demonstrated clonality in at least 95 percent of the wide range of tumours that have been examined. Renewal tissues such as bone marrow and intestinal mucosa represent a hierarchy of cells produced by cell division and differentiation from a small number of stem or early precursor cells. Most tumours arise in renewal tissues, and there is substantial evidence that many tumours contain a limited population of stem cells with the capacity to regenerate the tumour after treatment.

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She reported that she had a good appetite but complained of frequent con over-application of topical steroids can result in atrophy pain medication for dogs after surgery buy generic tizanidine 2mg on-line, follic ulitis, and telangiectasia. Applications should be alternated to stipation of bowels, attributing it to her unhealthy dietary habits. Minoxidil has been successful in hair regrowth by A review of other systems did not identify any other significant symptoms or concerns. The physical examination findings revealed a moderately heavy Though usually well tolerated, 3% of women who used Minoxidil (150 lbs) female, who was cooperative but anxious due to her also grew unwanted facial hair. There was no pallor or edema, vitals were Because of poor or unsatisfactory treatment outcomes, patients within normal limits, and overall Figure 1: Before Treatment with this condition often look for alternatives. There were 4-5 patches in sizes condition can be further complicated by the presence of blood stasis or blood heat. Her the role of acupuncture in this condition has not been inves tongue was pink with slightly thick tigated and reported in literature. This may be the first such case report that describes integration of these two ancient Asian medicines for this condition. Intervention During follow up at the end of 12 weeks, the hair uniformly grew to a Local ahshi acupuncture treatment was provided once a week, length of? This hair growth, local irritation and treatment included insertion of Seirin? needles (0. Needles were stimulated manually 1-2 events were observed during the times, but no deqi was elicited. Additionally, a topical Ayurveda herbal treatment was also added after six weeks to provide a synergestic effect and enhance the clinical outcomes. A paste of seeds of Croton tiglium, also Discussion known as Ba Dou in traditional Chinese medicine and Jayapala in Ayurveda, was given to her to apply topically once a day in this case report describes the management of alopecia areata addition to her regular acupuncture treatments. Croton tiglium is also until skin turned red and irritation was observed, which was three known as Ba Dou in Chinese medicine. Acupuncture was continued of Downward Draining Harsh Expellants and is considered hot, during this time. It is only used in its defatted form, as it is known irritation prior to the application and oral consent was obtained. This issue contains full-text content of the following: lated due to excess heat in the blood. He is passionate about was due to either acupuncture or the topical application or the patient-centered care, research, and combining combination of the two together. Jennifer Noborikawa received her Bachelors of Science in Biochemistry degree from Cal State Conclusion University, Fullerton, in 2013. After working as a Local acupuncture along with Croton tiglium seed paste when retail pharmacy technician for a year, in fall 2014, applied topically may help induce new hair growth in cases of she entered the doctor of acupuncture and Oriental alopecia areata. It is of clinical significance that remission not only medicine program at the Southern California occurred in our patient in less than three months but that hair University of Health Sciences. The shinkan transformed the practice of acupuncture in Japan, and is still widely ?Excellence in Journalism? used by sighted and non-sighted practitioners today. Sugiyama also was highly skilled in the award from the National Guild areas of abdominal diagnosis and palpation and during his lifetime established more than of Acupuncture and Oriental 40 schools of acupuncture for the blind. He has authored several papers and book chapters on acupuncture Key Words: acupuncture, palpation, guide tube, abdominal diagnosis, Waichi Sugiyama and related therapies and is currently writing a book on the history of acupuncture in the United States. Acupuncture is one of the most popular forms of complementary and alternative healing in the developed world. In the United States, it is estimated that more than 4% of the general population has received acupuncture at some point in time, and that 1. In modern Japanese-style acupuncture, there is From: Fujikawa Yu, Nihon no igakushi [History of Japanese Medicine] (? Japanese-style acupuncture are generally more gentle than those used in traditional Chinese acupuncture, and typically incorporate needles that are thinner and sharper. Although he learned Many of the elements of modern Japanese acupuncture can be about acupuncture from a number of famous traced back to Waichi Sugiyama, a blind acupuncturist who lived and practiced in the seventeenth century. Known traditionally as instructors, there are questions as to who he the ?father of Japanese acupuncture,? Sugiyama spent his early studied with first and for how long. He is most famous for inventing a type of tube called own style of acupuncture as well as in anma, a type of traditional the shinkan, which made it much easier to insert needles into a Japanese massage. After only a brief apprenticeship, however, Irie patient and transformed the practice of acupuncture in Japan. During his lifetime, he helped to establish more than 40 schools of acupuncture for According to other authors, however, Sugiyama first studied at the the blind. He was born the first son of a samurai family in did he travel back to Edo to learn under the direction of Irie. His father, Gonemon Shigemasa Sugiyama, was a vassal in the service of In another variation of the story, Sugiyama studied extensively Todo Takatora, a local daimyo (feudal lord) who achieved fame as with both Irie and Yamase before he ever set foot on Enoshima. After several years of instruction, Irie eventually reached and become an acupuncturist, one of the few professions in the conclusion that Sugiyama was ?without talent? as an acupunc Japan then available to blind people. Some authors suggest that he left home and began Having been rejected by two prominent instructors, a desperate studying abroad as a child, perhaps as early as ten years of age. Sugiyama chose not to return home but instead journeyed to Other authors suggest that he did not begin studying until he Enoshima, a small island off the southern coast of Japan near reached adulthood. To curry favor with the goddess, acupuncture from a number of famous instructors, there are ques Sugiyama entered a cave on the island, where he prayed and tions as to who he studied with first and for how long. The authors have claimed that Sugiyama stayed on Enoshima for as tube also prevented needles made of soft metals, such as silver or little as five or seven days. This enabled acupuncturists to insert needles Sugiyama prayed before Benten for as long as 100 days. Finally, to steady himself while tripping, that he supported himself on a the shinkan allowed for the use of finer and thinner needles, which nearby rock while coming out of the cave, that he fainted, or that further reduced the amount of pain involved during insertion and he simply fell to the ground in despair. One of his underappreciated skills was not pierced at all and that he grabbed the shinkan while trying to his ability to refine centuries of Chinese theory on acupuncture regain his balance or that he found it lying on the ground. Because Sugiyama some accounts, Benten seems to have been an active participant, could not read, and because reading systems for the blind such as either by approaching Sugiyama with a shinkan in a dream24 or Braille had not yet been invented, Sugiyama had to rely on his own handing him the shinkan during a heightened religious state and intellect to separate important information from trivial knowledge then directing him to return to Edo for additional training. Tsunayoshi was suffering from a severe abdominal from a relatively minor diagnostic tool into a distinct healing art. Fortunately, Sugiyama was able to cure the shogun and return him to good Sugiyama studied the Nan Jing by having it read to him. Under this method, each phase was evaluated at a different Sugiyama an annual pension of 500 koku of rice, promoted him to location. The upper part of the abdomen, for example, was used the rank of ?superintendent of the blind? for Edo and the sur to evaluate the Fire phase, while the Water phase was evaluated rounding provinces, and bestowed upon him the honorary title of Kengyo, or master. Wood and Metal were evaluated at the left and right parts of the abdomen respectively, and Earth was evaluated the rest of his life. Sugiyama also published a series of eight principles of abdominal Tsunayoshi also rewarded Sugiyama with a plot of land, upon diagnosis. He emphasized that practitioners should press below which Sugiyama established the Shinji Gakumonsho, a school to train the blind in acupuncture. During the procedure, and listened to passages recited from the Ryu Sanbusho, with each he would note variations in temperature, the elasticity of the passage being repeated several times so students could mem orize them. Over time, Sugiyama overcame his blindness and established himself as an extremely proficient and sensitive healer. After several years of personal study and experimentation, he returned Death and Legacy to Edo. Along with writing the Ryu Sanbusho, Sugiyama continued to refine his techniques, and began teaching the shinkan method, Waichi Sugiyama died in Edo in 1694 at the age of 84. At the time as well as abdominal diagnosis, anma, and other therapies, to stu of his death, Sugiyama had only been able to personally instruct approximately 20 students. This volume included techniques alive, significantly increasing the number of blind detailed information on 96 separate techniques devised by acupuncturists. He was instrumental in making more jobs available to the blind and visually impaired. One contained Because of his efforts, acupuncture, moxibustion, and massage introductory information on pulse diagnosis, abdominal diagnosis, became highly respected occupations for the blind in Japan. This treatment methods, beginning acupuncture techniques, and st rather unique tradition continues in Japan in the 21 century the principal Sugiyama-style techniques that students would as visually impaired individuals are allowed?and frequently learn to become an acupuncturist.

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Of course neuropathic pain treatment guidelines 2010 purchase tizanidine pills in toronto, a change at one level may well trigger secondary changes throughout an organism, so that the original one is hard to identify. The same holds true for electric and magnetic fields, whose study is further complicated by the fact that animals of different shapes distort the fields differently. The only way to test for possible damage (or beneficial effects) is to actually do the experiment. In a sense, the entire population of the world is willy-nilly the subject of a giant experiment. Electropollution has been the subject of heated public debate for nearly ten years, and unpublicized misgivings for dec ades before that. Subliminal Stress After Howard Friedman, Charlie Bachman, and I had found evidence that "abnormal natural" fields from solar magnetic storms were affecting the human mind as reflected in psychiatric hospital admissions, we de cided the time had come for direct experiments with people. We ex posed volunteers to magnetic fields placed so the lines of force passed through the brain from ear to ear, cutting across the brainstem-frontal current. We measured their influence on a standard test of reaction time?having subjects press a button as fast as possible in response to a red light. We were excited, eagerly planning experiments that would tell us more, when we came upon a frightening Russian report. Yuri Kholodov had administered steady magnetic fields of 100 and 200 gauss to rabbits and found areas of cell death in their brains during autopsy. Although his fields were ten time as strong as ours, we stopped all human experi ments immediately. He made the slides and sent them to an expert on rabbit brain diseases, but coded them so no one knew which were which until later. The report showed that all the animals had been infected with a brain parasite that was peculiar to rabbits and common throughout the world. The expert suggested that we must have done something to undermine resistance of the rabbits in the exper imental group. The code confirmed that most of the brain damage had occurred in animals subjected to the magnetic fields. Later, Friedman did biochemical tests on another series of rabbits and found that the fields were causing a generalized stress reaction marked by large amounts of cortisone in the bloodstream. Soon thereafter, Friedman measured cortisone levels in monkeys ex posed to a 200-gauss magnetic field for four hours a day. They showed the stress response for six days, but it then subsided, suggesting adapta tion to the field. Hans Selye has clearly drawn the invariable pattern: Initially, the stress activates the hormonal and/or immune systems to a higher-than-normal level, enabling the ani mal to escape danger or combat disease. If the stress continues, hormone levels and immune reactivity gradually decline to normal. In medical terms, stress decompensation has set in, and the animal is now more susceptible to other stressors, including malig nant growth and infectious diseases. In the mid-1970s, two Russian groups found stress hormones released in rats exposed to microwaves, even if they were irradiated only briefly by minute amounts of energy. Several Russian and Polish groups have since established that after prolonged exposure the activa tion of the stress sytem changes to a depression of it in the familiar pattern, indicating exhaustion of the adrenal cortex. Udintsev also documented an insulin insufficiency and rise in blood sugar from the same field. When undergoing these hormonal changes, an animal would normally be aware that its body was under attack, yet, as far as we could tell, the rabbits were not. Noval at the Naval Aerospace Medical Research Laboratory at Pensacola, Florida, found the slow stress response in rats from very weak electric fields, as low as five thousandths of a volt per centimeter. The scariest part was that the fields Noval used were well within the background levels of a typical office, with its overhead lighting, typewriters, computers, and other equipment. Workers in such an environment are exposed to elec tric fields between a hundredth and a tenth of a volt per centimeter and magnetic fields between a hundredth and a tenth of a gauss. Power Versus People Because industry and the military demand unrestricted use of elec tromagnetic fields and radiation, their intrinsic hazards are often compounded by secrecy and deceit. I learned this lesson in my first en counter with the environmental review process. The plan, called Project Sanguine, was to establish a radio link with nuclear sub marines at their normal depth of 120 feet or below. The original design involved 6,000 miles of buried cable arranged in a grid across the upper two fifths of Wisconsin. A transmitter would pump current into one side; the electricity would emerge from the other side and complete the circuit by traveling through the ground. Sanguine was one of the first military projects scrutinized under the Environmental Protection Act. Captain Paul Tyler of the Office of Naval Re search asked me to be one of its seven members. The antenna would produce an electromagnetic field 1 million times weaker than that from a 765-kilovolt power line. Similar fields had been shown to raise human blood triglyceride levels (often a harbinger of stroke, heart attack, or arteriosclerosis), and change blood pressure and brain wave patterns in experimental animals. The generalized stress response, desynchronized biocycles, and interference with cellular metabolism and growth processes?and hence increased cancer rates?were also distinct possibilities. Hundreds of thousands of people would be living inside the antenna even in this sparsely populated area; long-term effects on plants and animals were unknown; and, be cause the signals would resonate throughout the world, the biohazards might be similarly widespread. For these reasons we unanimously rec ommended that the project be shelved pending answers to the ominous questions it raised. The committee met on December 6 and 7, 1973, generating a report then and there, with a secretary taking down our conclusions. The Navy group in charge was apparently displeased with our findings, the printed proceedings, marked "For official use only,' went out only to committee members, and the Navy refused to discuss them with anyone else. The commission in turn asked the Navy for a copy of our report but was turned down flat. He ran ten separate experiments with rats, expos ing them for one month to 60-hertz electric fields of 100 to 150 volts per centimeter, simulating ground level underneath a typical high-ten sion line. Three generations of rats bred in this field showed severely stunted growth, especially among males. At lower field strengths (35 volts per centimeter) some of the animals gained more weight than con trols, a response we tentatively traced to abnormal water retention, which, like underweight, could also result from stress. A few years later, a study commissioned by the Department of Energy to duplicate this research also produced contradictory but disquieting results. With every known variable controlled in an expensive, high-tech facility at Battelle Laboratories in Columbus, Ohio, one test showed severe growth retarda tion over three generations, while a second run under exactly the same conditions produced significantly greater weight gain than normal. Between 6 and 16 percent of the pups born in various tests failed to live to maturity because of the electric field. That is, these percentages were in excess of the normal death rate for newborn rats. There was also a very high incidence?ten in sixty?of glaucoma in the early experiments. The companies had hired two microwave researchers, Herman Schwan and Solomon Michaelson, both of whom did most of their work for the Department of Defense, and University of Rochester botanist Mort Miller. Carefully prepared by these three, the company lawyers cross-examined us for seventeen days in December 1975, attacking not only our methods and results but our scientific competence and honesty as well. Michaelson strenuously denied that our rodents had shown signs of stress, even though the biological markers were clear. Even if they had, he contended, stress could be healthful, an idea that Hans Selye later called "farfetched" when applied to a biological challenge that was continuous and not self-imposed. As far as I know, our testimony was the first ever openly given by American scientists stating that electromagnetic energy had health effects in doses below those needed to heat tissue, and that power lines might therefore be hazardous to human health. We criticized the White House Office of Telecommunications Policy for failing to follow up a tentative 1971 warning by advising the President that some harmful effects from electropollution were now proven. We were well acquainted with three of the men who were on it: Schwan, Michaelson, and Miller. After the testimony, while the commission, assisted by a panel of judges, was deliberating, other evi dence could be introduced, but it was no longer subject to review by the opposing side. Then, when the members of the commit tee were announced, the Secretary and other Navy brass agreed that the show was rigged.

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Tiny amounts of certain minerals mixed into the semiconductor material could change its characteristics enor mously pain medication for dogs with arthritis order tizanidine 2 mg without prescription. The making of semiconductors to order by selective doping would become a science in itself; to us it suggested trace elements in bone. We already knew that certain trace metals such as copper, lead, silver, and beryllium bonded readily to bone. Ra dioactive strontium 90 worked its harm by bonding to bone, then bombarding the cells with ionizing radiation. We used it to measure the fre electrons in collagen and apatite, and we found the same kind of discrepancy as in our flourescence the Ticklish Gene 133 experiment: When we added together the free electrons of collagen and apatite, we fell short of the number we found in whole bone. We knew we were on the way to solving this mystery when we exam ined the results. Only a few of the metals had bonded to the bone mate rials: beryllium, copper, iron, zinc, lead, and silver. The results showed that the bonding sites were little recesses into which would fit one atom of silver or lead, two of iron or copper or zinc, or six of beryllium. Only one of these metals gave us an electron resonance of its own, indicating that it had a large number of free electrons that could affect the electrical nature of bone. Since the molecular structure of each was quite different, we figured that each would bind copper in a different way. By analyzing it we deduced that each atom of copper fit into a little pit, surrounded by a particular pattern of electric charges, on the surface of apatite crystals and collagen fibers. Because the pattern of charges was the same in both materials, we knew that the bonding sites were the same on both surfaces and that they lined up to form one elongated cavity connecting the crystal and fiber. In other words, the two bonding sites matched, forming an enclosed space into which two atoms of cop per nestled. The electrical forces of this copper bond held the crystals and fibers together much as wooden pegs fastened the pieces of antique furniture to each other. The question of how the innermost apatite crystals fasten onto collagen had eluded orthopedists until then, and the finding may have opened a way to un derstand osteoporosis,a condition in which the apatite crystals fall off and the bone degenerates. I surmise that osteoporosis comes about when copper is somehow removed 134 the Body Electric from the bones. This might occur not only through chemical/metabolic processes, but by a change in the electromagnetic binding forces, allow ing the pegs to "fall out. As flights got longer, doctors found that more and more apatite was lost from the bones, until decalcification reached 8 percent in the early Soviet Salyut space-station tests. Serious problems were known to occur only when apatite loss reached about 20 percent, but the trend was alarming, especially since depletion of the calcium reservoir might affect the nervous system and muscular efficiency before the 20-percent level was reached. Although the immediate cause was their inability to get a malfunctioning air valve closed before all the cabin air escaped, weakness from muscle tone loss might have contributed to the death of the three cosmonauts who succumbed while returning from their twenty-four-day flight aboard Soyuz 11 at the end of June 1971. The unfamiliar external field reversals could also weaken the copper pegs, at the same time that the bones are in a constant state of "re bound" from their earthly weight-induced potentials, producing a signal that says, "No weight, no bones needed. They worked out so hard that their muscles grew, but decalcification still reached 6. The Soviets at first claimed to have solved the problem before or dur ing the Soyuz 26 mission of 1977?78, in which two cosmonauts orbited in the Salyut 6 space lab for over three months. Subsequent Soviet space persons, who have remained weightless as long as 211 days, reportedly have showed no ill effects from osteoporosis, and chief Soviet space doc tor Oleg Gazenko said it simply leveled off after three months. We decided that regenerative growth control was our primary target, so we reluctantly dropped osteoporosis. Fortified by our new knowledge that electricity controlled growth in bone, we returned in stead to the nerves, taking a closer look at how their currents stimulated regrowth. A Surprise in the Blood 1 felt as though the temple curtain had been drawn aside without warn ing and I, a goggle-eyed stranger somehow mistaken for an initiate, had been ushered into the sanctuary to witness the mystery of mysteries. Within themselves they juggled geometrical shards like the fragments in a kaleidoscope. They were like bees swarming: They obviously recognised each other and were communicating avidly, but it was impossible to know what they were saying. The filmmaker frankly admitted that neither he nor anyone else knew just what the cells were doing, or how and why they were doing it. We biologists, especially during our formative years in school, spent most of our time dissecting dead animals and studying preparations of dead cells stained to make their structures more easily visible?"painted tombstones," as someone once called them. Of course, we all knew that life was more a process than a structure, but we tended to forget this, because a structure was so much easier to study. This film reminded me how far our static concepts still were from the actual busi ness of living. The film was shown at a workshop on fracture healing sponsored by the National Academy of Sciences in 1965. It was one of a series of meetings organized for the heads of clinical departments to educate them as to the most promising directions for research. Since I was an active researcher and had just been promoted to associate professor, Jim asked me to go in his place. I tried to get out of it, because I knew my electrical bones would get a frosty reception from the big shots if I opened my mouth, but Jim prevailed. Another was the chance to get acquainted with the other delegate from my department, a sharp young orthopedic surgeon named Dave Murray. With a tact that seemed peculiarly English, he reached the same assessment we had, but phrased the Ticklish Gene 137 it so as to offend no one. Most past work on fractures had described what happened when a bone knit, as opposed to the how and why. As Pritchard pointed out, "Not a great deal of thought has been given to the factors that initiate, guide, and control the various processes of bone repair. Having just deciphered the control system for stress adaptation (Wolffs-law growth) in bone, I felt pre pared to get back to the more complex problems of regeneration via its remnant in bone healing. We would break the same bone in a standardized way in each of a series of experimental animals. We would kill a few of the animals at each stage of healing, and Dave, an expert histologist (cell specialist), would make microscope slides of the healing tissues and study the cellular changes. Along the way we would fit our findings together to see whether electricity was guiding the cells. We wanted to use dogs or rabbits, since ultimately we were trying to understand hu man bones and wanted to work with animals as closely related to us as possible. But we would need scores of them to study each phase of heal ing adequately, and we had neither the funds nor the facilities to house so many large mammals. We thought of rats, but their longest bones were too short to study clearly and were curved as well. We were look ing for nice, long, straight bones, in which we could produce uniform breaks. They were cheap to buy and care for; we could even collect some ourselves from nearby ponds. Our misgivings about the evolutionary distance between frogs and humans were allayed when we went to the library to read up on what was then known about fracture healing in frogs. Ruzicka, had 138 the Body Electric determined that frogs mended their bones the same way people did. Our question was: What stimulated the periosteal and marrow cells to change into new bone-forming cells? We began by anesthetizing the animals and resolutely breaking all those little green legs by hand, bending them only to a certain angle so as not to rupture the periosteum around the fracture. I found I had to put little plaster casts on them?not because the frogs seemed in great pain but because their movements kept shifting the broken bones and making systematic observations impossible. Before fracture the ankle end of both the bone and the periosteum had a small negative potential of less than 1 millivolt as compared to the knee end. At the moment of fracture, the negative potential on the intact periosteum over the break shot up to 6 or 7 millivolts, while areas of positive charge formed above and below the break. When a fracture ruptured the periosteum, its negative potential went even higher than 7 millivolts, but amputation of the dangling lower leg immediately reversed the po larity, producing a positive current of injury from the stump, as in the frogs of my first regeneration experiment. The bone itself underwent a short-term electrical change opposite to that in the periosteum. A small positive charge appeared on each of the broken ends during the first hours, then fell to near zero after three hours.

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Short-chain fructo-oligosaccharide administra tion dose-dependently increases fecal bifidobacteria in healthy humans knee pain treatment home remedy purchase 2mg tizanidine overnight delivery. Oat beta-glucan reduces blood cholesterol concentration in hyper cholesterolemic subjects. Symptomatic response to varying levels of fructo oligosaccharides consumed occasionally or regularly. Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers. Iron absorption from bread in humans: Inhibiting effects of cereal fiber, phytate and inositol phosphates with different numbers of phosphate groups. Dietary supplementa tion of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects. Effect of dietary fibre on stools and transit-times, and its role in the causation of disease. Sustained post-ingestive action of dietary fibre: Effects of a sugar-beet-fibre-supplemented breakfast on satiety. Assessment of the effect of increased dietary fibre intake on bowel function in patients with spinal cord injury. Relationship between the intake of high fibre foods and energy and the risk of cancer of the large bowel and breast. The effects of grapefruit pectin on patients at risk for coronary heart disease without alter ing diet or lifestyle. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol. Comparison of diarrhea induced by ingestion of fructooligosaccharide Idolax and disaccharide lactulose (role of osmolarity versus fermentation of malabsorbed carbohydrate). Toxicological evaluation of neosugar: Genotoxicity, carcinogenicity, and chronic toxicity. Coudray C, Bellanger J, Castiglia-Delavaud C, Remesy C, Vermorel M, Rayssignuier Y. Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. Fermentation and the production of short-chain fatty acids in the human large intestine. Colonic responses to dietary fibre from carrot, cabbage, apple, bran, and guar gum. Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber). Digestion and physiological properties of resistant starch in the human large bowel. A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Long-term effects of consuming foods containing psyllium seed husk on serum lipids in subjects with hypercholesterolemia. Resistant starch decreases serum total cholesterol and triacylglycerol concentrations in rats. Effects of different soluble:insoluble fibre ratios at breakfast on 24-h pattern of dietary intake and satiety. Resistant starch has little effect on appetite, food intake and insulin secretion of healthy young men. A multi-centre, general practice comparison of ispaghula husk with lactulose and other laxatives in the treatment of simple constipation. Relation between dietary fiber consumption and fibrinogen and plasminogen activator inhibitor type 1: the National Heart, Lung, and Blood Institute Family Heart Study. The effects of high and low energy density diets on satiety, energy intake, and eating time of obese and nonobese subjects. Effect of pectin on serum lipids and lipoproteins, whole-gut transit-time, and stool weight. Dietary fiber in pancreatic disease: Effect of high fiber diet on fat malabsorption in pancreatic insufficiency and in vitro study of the interaction of dietary fiber with pancreatic enzymes. Evaluation of guar biscuits for use in the management of diabetes: Tests of physiological effects and palatability in non-diabetic volunteers. Digestion of the carbohydrates of banana (Musa paradisiaca sapientum) in the human small intestine. Diet and physical activity as determi nants of hyperinsulinemia: the Zutphen Elderly Study. Effects of unprocessed bran on colon function in normal subjects and in diverticular disease. Franceschi S, Favero A, Decarli A, Negri E, La Vecchia C, Ferraroni M, Russo A, Salvini S, Amadori D, Conti E, Montella M, Giacosa A. A possible protective effect of nut consumption on risk of coronary heart disease. Risks associated with source of fiber and fiber components in cancer of the colon and rectum. Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. Guar sprinkled on food: Effect on glycaemic control, plasma lipids and gut hormones in non-insulin depen dent diabetic patients. Cholesterol reduc tion by glucomannan and chitosan is mediated by changes in cholesterol ab sorption and bile acid and fat excretion in rats. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. The effect of muesli or cornflakes at breakfast on carbohydrate metabolism in type 2 diabetic patients. Effect of added fiber on the glucose and metabolic response to a mixed meal in normal and diabetic subjects. Graham S, Hellmann R, Marshall J, Freudenheim J, Vena J, Swanson M, Zielezny M, Nemoto T, Stubbe N, Raimondo T. Graham S, Zielezny M, Marshall J, Priore R, Freudenheim J, Brasure J, Haughey B, Nasca P, Zdeb M. Diet in the epidemiology of postmenopausal breast cancer in the New York State Cohort. Non-digestible oligosaccharides used as prebiotic agents: Mode of production and beneficial effects on animal and human health. Long-term effects of guar gum in subjects with non-insulin-dependent diabetes mellitus. The role of glucose, insulin and glucagon in the regulation of food intake and body weight. Mineral balances of men and women consuming high fiber diets with complex or simple carbo hydrate. Fiber intake, age, and other coronary risk factors in men of the Baltimore Longitudinal Study (1959?1975). Diets containing soluble oat extracts improve glucose and insulin responses of moderately hypercholesterolemic men and women. The adsorp tion of heterocyclic aromatic amines by model dietary fibres with contrasting compositions. Guideline Concerning the Safety and Physiological Effects of Novel Fibre Sources and Food Products Containing Them. Guideline for planning and statistical review of clinical laxation studies for dietary fibre. In: Guideline Concerning the Safety and Physiological Effects of Novel Fibre Sources and Food Products Containing Them. Neither raw nor retrograded resistant starch lowers fasting serum cholesterol concentra tions in healthy normolipidemic subjects. Reproduction Toxicity: Study on the Influence of Fructooligosaccharides on the Development of Foetal and Postnatal Rat. Cereals, cereal fibre and colorectal cancer risk: A review of the epidemiological literature.

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Hence pain treatment for dogs buy generic tizanidine on-line, albumin and transferrin remain the best measures of protein mal nutrition, but with all of the caveats listed in Table 10-6. In protein malnutrition, the skin becomes thinner and appears dull; the hair first does not grow, then it may fall out or show color changes (Pencharz, 1985). Over a longer period of time, assessment of changes in lean body mass reflects protein nutritional status. The clinical tools most available to assess lean mass are dual emission x-ray absorptiometry and bioelectrical impedance (Pencharz and Azcue, 1996). This section reviews some of the possible indicators used or proposed for use in analyses estimating human protein requirements. Factorial Method the factorial method is based on estimating the nitrogen (obligatory) losses that occur when a person is fed a diet that meets energy needs but is essentially protein free and, when appropriate, also relies on estimates of the amount of nitrogen that is accreted during periods of growth or lost to mothers during lactation. The major losses of nitrogen under most con ditions are in urine and feces, but also include sweat and miscellaneous losses, such as nasal secretions, menstrual losses, or seminal fluid. This is where the factorial method has its greatest weakness, since the relationship between protein intake and nitrogen retention is somewhat curvilinear; the efficiency of nitrogen retention becomes less as the zero balance point is approached (Rand and Young, 1999; Young et al. Additionally, in order to utilize the factorial approach when determining the protein requirement for infants and children, their needs for protein accreted as a result of growth must be added to their maintenance needs. Nitrogen Balance Method this classical method has been viewed by many as theoretically the most satisfactory way of determining the protein requirement. Nitrogen balance is the difference between nitrogen intake and the amount excreted in urine, feces, skin, and miscellaneous losses. As discussed below, nitro gen balance remains the only method that has generated sufficient data for the determination of the total protein (nitrogen) requirement. It is assumed that when needs are met or exceeded adults come into nitrogen balance; when intakes are inadequate, negative nitrogen balance results. In determining total protein (nitrogen) needs, high-quality proteins are utilized as test proteins to prevent negative nitrogen balance resulting from the inadequate intake of a limiting indispensable amino acid. A significant literature exists regarding the methods and procedures to use in deter mining nitrogen balance amount (Manatt and Garcia, 1992; Rand et al. Limitations of the Method the nitrogen balance method does have substantial practical limita tions and problems. First, the rate of urea turnover in adults is slow, so several days of adaptation are required for each level of dietary protein tested to attain a new steady state of nitrogen excretion (Meakins and Jackson, 1996; Rand et al. Second, the execution of accurate nitro gen balance measurements requires very careful attention to all the details of the procedures involved. Since it is easy to overestimate intake and underestimate excretion, falsely positive nitrogen balances may be obtained (Hegsted, 1976). Indeed, an overestimate of nitrogen balance seems con sistent throughout the literature because there are many observations of quite considerable apparent retention of nitrogen in adults (Oddoye and Margen, 1979). A third limitation of the nitrogen balance method is that since the requirement is defined for the individual, and studies rarely provide exactly the amount of protein necessary to produce zero balance, individuals must be studied at several levels of protein intake in the region of the requirement so that estimates of individual requirements can be interpolated (Rand et al. Finally, dermal and miscellaneous losses of nitro gen must be included in the calculation. These are inordinately difficult to measure, and vary with the environmental conditions. In fact, the literature indicates marked (at least twofold) differ ences between studies (Calloway et al. The inclusion of dermal and miscellaneous nitrogen losses can have a significant effect on estimates of amino acid requirements via nitrogen balance, especially in adults (Calloway et al. Statistical Analysis of Nitrogen Balance Data In studies with healthy adults in presumably good nutritional status, it is generally assumed that the protein requirement is achieved when an individual is in zero nitrogen balance. To some extent, this assumption poses problems that may lead to underestimates of the true protein requirement. First, there are sufficient observations of paradoxically high positive nitrogen balances in the literature to imply that when individuals are in measured body nitrogen equilibrium, they are in fact in a small nega tive nitrogen balance (Kopple, 1987). The large majority of the studies have concentrated their measurements of protein adequacy at levels of intake below nitrogen balance and as a result, the intercept of protein intake at zero nitrogen balance is lower than the true intercept as the efficiency of protein utilization decreases as zero balance is reached (Young et al. The empirical solution is to carry out measurements that span nitro gen equilibrium, ideally by using multiple levels of intake in the same individual and interpolating individual requirement levels. Three differ ent interpolation schemes have been proposed, based on (1) a smooth nonlinear model (Hegsted, 1963; Rand and Young, 1999), (2) a two-phase linear model (also called bilinear or breakpoint) (Kurpad et al. Since the physiological response relationship between nitrogen intake and balance is theoretically expected not to be linear, the more complex models (1 and 2 above) would be appropriate bases for arriving at a requirement estimate. Thus, while it is recognized that the first two models above are more realistic biologically, because of the lack of available data the method adopted for this report is to use linear interpolation to estimate the indi vidual requirements (the intakes predicted to result in zero balance) that in turn are used to estimate the distribution of protein requirements. The bilinear model was used to estimate requirements for some of the amino acids; however, estimates of population variability (between individuals) were derived from the analysis of protein requirements. These approaches give somewhat different information about the requirement for the amino acid. Moreover, each method has peculiar theoretical and practical disadvantages, thus the level of consis tency of estimates based on different approaches should be examined. Nitrogen Balance Method this classical method is discussed earlier in more detail under ?Selection of Indicators for Estimating the Requirement for Protein (Nitrogen). Many explanations have been put forward for the lower results using nitrogen balance methodology, including the fact that excess nonprotein energy may have been used in many nitrogen balance studies (Garza et al. The design of that study allowed for the determination of between individual variance by studying each individual at several levels of lysine intake. In fact, within the large nitrogen balance and amino acid require ment literature, only one other study (Reynolds et al. The reanalysis of the 1956 Jones study produced an estimate of nitrogen equi librium for lysine of 30 mg/kg/d, which is comparable to the values derived by the other methods described below (Rand and Young, 1999). In addition, most of the classic amino acid work using nitrogen balance (Leverton et al. Unfortunately, for infants and children the only data available are those based on nitrogen balance, and considerable uncertainty about the accuracy of the estimates remains. However, recent factorial estimates are in reasonable agreement with the nitrogen balance estimates (Dewey et al. Plasma Amino Acid Response Method this method was the first that focused on the physiology of the indi vidual amino acid (Longnecker and Hause, 1959; Munro, 1970). The reasoning behind this approach is that when the intake of the test amino acid is below its dietary requirement, then its circulating concentration is not only low, but also is relatively insensitive to changes in intake. As intakes of the target amino acid approach the requirement level by increasing the intake of the limiting amino acid, the plasma level of the amino acid starts to increase progressively (see Figure 10-4). The point at which the ?constant? portion of the relationship between intake and plasma concen tration intersects the linear portion is considered to be an estimate of the requirement. A variation on this method involves the examination of the changes in the plasma concentration of the test amino acid as the adult moves from the post absorptive to the fed state post-consumption (Longnecker and Hause, 1961). The main difficulty is that amino acid metabolism is so complex that factors other than the level of amino acid intake, such as gastric emptying time, can influence its concentration (Munro, 1970). Furthermore, the relationship between the intake of the amino acid and its circulating concentration is not necessarily bilinear, so it is difficult to determine a ?breakpoint? (Young et al. Although in some regards this problem applies also to the oxidation methods discussed below, over the last 20 years these later methods have supplanted plasma amino acid concentration?based approaches. This marked a major theoretical advance over the nitrogen balance and plasma amino acid response methods. Thus by analogy to the 2 concentration method, it is assumed that below the requirement the test amino acid is conserved and that there is a low constant oxidation rate, but once the requirement is reached, the oxidation of the test amino acid increases progressively. The most salient problem arises from the reliance on the determination of a breakpoint in the oxidation of the test amino acid. However, at these low dietary intakes, the intake of the infused labeled amino acid becomes significant in relation to dietary intake. This limits its use largely to the branched chain amino acids, phenylalanine, and lysine. Other amino acids, such as threonine and tryptophan, pose particular problems (Zhao et al. A criticism of this method has been that measurements were only made during a short period during which food was given at regular hourly intervals. A later modification of this approach was to infuse the labeled amino acid during a period of fasting followed by a period of hourly meals, thus acknowledging the discontinuous way in which food is normally taken (Young et al.

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Other Russian scientists have drawn a tentative correlation between the sector cycle and reports from two groups of persons with neurological diseases pain management for my dog 2mg tizanidine fast delivery. The patients felt worse within sectors of positive polarity, when bacteria seemed to grow faster. We might suspect, therefore, that many creatures would use magnetic infor mation for their sense of place. A built-in compass helps guide them in foraging or other local business, as well as migration over much longer routes. Monarch butterflies travel from Hudson Bay to South America straight across the Caribbean without ever getting lost. Some salamanders, only inches long and built very low to the ground, travel up to 30 miles of rugged mountain country in California to set up housekeeping, then return to their home stream to breed. Karl von Frisch was the first to attack the problem, with his famous 1940s studies of the honeybee dance, which won him a Nobel Prize in 1973. Kramer inferred that the birds must have a compass in addition to a map of remembered landmarks from the way they immediately pointed their beaks toward home after circling once after release. Soon others found the same kind of sun compass as bees used, but the pigeons could also steer perfectly on cloudy days. He was ridiculed and "refuted" by a few inadequate experiments?such as placing a pigeon in a variety of electromagnetic fields and noting that it seemed to be com fortable! Furthermore, by changing the orientation of the surrounding field with coils, he could give the birds a false sense of where southwest was. To study this magnetic interference in any weather, Keeton made translucent contact lenses for his birds, then released them in the moun tains of northern New York. How ever, each avian Ulysses who wore the lenses but no magnets faultlessly navigated the 150 miles southwest to Ithaca, then flew ever tighter cir cles around the loft and fluttered in like a helicopter to a perfect blind landing. Gould of Princeton, outfitted pigeons with miniaturized electromagnetic coils that let the researchers vary the type and orientation of applied field at will. They discovered that if the south pole of the field was directed up, the birds could still find home, but with the north pole up they flew directly away from it. At about the same time two German scientists, Martin Lindauer and Herman Martin, analyzed half a million bee dances and found a "magnetic error" in them?a compensation for the difference between magnetic north and true north. They were also able to intro duce specific angles of error in the dances with specifically oriented coils around the hive. Here was proof that magnetic guidance systems existed in both the birds and the bees. Blakemore, then a graduate student at the Uni versity of Massachusetts in Amherst, astonished the world of biology with the announcement that some bacteria, the lowliest of all cells, also had a magnetic sense. Blakemore made the discovery when, studying the salt marshes of Cape Cod, he noticed that one type of bacterium always oriented itself north-south on his microscope slides. The direction to magnetic north points through the earth somewhat down from the horizon, and the scientists became con vinced that the bacteria were using the field to guide themselves ever downward to the mud where they throve, since they were too small to sink through the random molecular motion of the water around them. Not only could the amphibians find home without tight or other common cues; in addition, when Adler tried to confuse them with artificial fields, they quickly adapted to the interference and oriented themselves correctly in relation to the weaker geomagnetic background. Breathing with the Earth 253 this idea was later confirmed by findings that microbes at Rio and in New Zealand were south-seekers. Each bacterium contained within it, like a chain of cut jet stones, a straight line of magnetite microcrystals. Surrounded by a thin mem brane, each of these particles was a single domain, the smallest piece of the mineral that could still be a magnet. After confirming that they were magnetic, he dissected them and narrowed the location down to a part of the abdomen. Using the same method, Walcott and Green dissected the heads of two dozen pigeons, gradually subdividing them with nonmagnetic probes and scal pels. After a painstaking search the investigators found a tiny magnetic deposit in a 1 by 2-millimeter piece of tissue richly festooned with nerves, on the right side of the head, between the brain and the inner table of the skull. The same dot of tissue contained yellow crystals of the iron-storage protein ferritin, indicating that the pigeons, like the bacte ria, synthesized their own lodestone crystals. The existence of magnetic sensors in such diverse creatures as bacteria, bees, and birds?the current count of species with magnetic organs is twenty-seven, including three primates?suggests that a magnetic sense has existed from the very beginning of life, perhaps only to be perfected by creatures that need to get around a lot. Do all animals, then, have the same sensors, and do they always serve the same function? How is the information read out of the crystals by the nervous system and trans lated into directions? When flying on visual flight rules by sun compass, they would circle once, get their bearings, then move off straight toward Ithaca. But when using their magnetic compass, the birds would fly due west from their release point until they got out over Lake Ontario, due north of Ithaca. Then, out of sight of land, they would make a right-angle turn to the left and follow the exact meridian of home. Some migrating birds make a dogleg to the east in their north-south flyway, sailing out of sight of land over Lake Superior. Do they go out of their way to avoid being disoriented by iron ore deposits in the Mesabi Range? Robin Baker, a young University of Man chester researcher into bionavigation, led a group of high school students into a bus at Barnard Castle, near Leeds, England. Half of the head gear contained magnets and half contained brass bars that their wearers thought were magnets. After a few miles the coach stopped while the students wrote on cards an estimate of the compass direction toward the school. Then the driver turned through 135 degrees and continued east to a spot southeast of the school, where the students again estimated their direction. When the cards were analyzed, it turned out that the persons with brass bars by their heads had been able to sense the proper heading quite reliably, while those wearing magnets had not. In the middle of a specially built, light tight wooden hut free of magnetic interference, the subject is blind folded, earmuffed, and seated on a friction-free swivel chair. After being turned around several times, the subject must estimate his or her com pass heading as before. With statistically consistent success in more than 150 persons, Baker believes he has proven the existence of a human magnetic sense. Otherwise they start rationalizing the process, trying to deduce the right way from too little evidence and becoming confused. In 1983, using magnetic measurements in selective-shielding experi ments, Baker and his co-workers reported locating magnetic deposits close to the pineal and pituitary glands in the sinuses of the human ethmoid bone, the spongy bone in the center of the head behind the nose and between the eyes. Army Advanced Material Concepts Agency, pointed to this same spot as one of two areas?the other was the adrenal glands?where the dowsing ability resided. In 1984 a group headed by zoologist Michael Walker of the Univer sity of Hawaii in Honolulu isolated single-domain magnetite crystals from a sinus of the same bone in the yellowfin tuna and Chinook salmon. The crystals were of a shape normally shown only by magnetite synthesized by living things rather than geological processes. Abundant nerve endings entered the magnetic tissue, and the crystals were orga nized in chains much like those in magnetotactic bacteria. Each crystal was apparently fixed in place but free to rotate slightly in response to external magnetic forces. This result correlated perfectly with earlier homing studies on live tuna by the same group. There are numer ous detailed pictures of that primal scene in print today, but most are variations on one theory "warm soup and lightning. Into that atmosphere some source of energy?lightning, heat, and ultraviolet radiation have all been suggested?led to the spontaneous formation of simple organic compounds. Sifting into the oceans for mil lions of centuries, these compounds would have coalesced by chance into ever more elaborate patterns. According to the theory, this process culminated in closed "protocells" able to resist the reactivity of other structures while growing through incorporation of similar compounds. Miller pumped a facsimile of the presumed early atmosphere?ammonia, methane, and water vapor?continuously past an electric spark. In water they co alesced into globules with a sort of membrane around them?called "coacervates" by A. Oparin and "proteinoids" by Sidney Fox, two of the most assiduous students of biogenesis. More important, the experiments raised two difficulties, one theoretical, one practical. According to our notions of biology, nothing could be alive before that point, yet it seemed incredible that chance associations of the building blocks could form a palace of such complexity without passing through a mud-hut stage.