Faculty Bibliography

The 'myocardial ischemia' that sent President Boris N. Yeltsin to the hospital yesterday for the second time in three months is a common, serious heart condition that affects millions of people around the world. Myocardial ischemia describes a lack of oxygen-rich blood to meet the heart's needs to pump blood. Such ischemia usually produces the chest pains of angina, although aides to Mr. Yeltsin, who is 64, did not use the word angina. Ischemia (pronounced iss-KEE-mee-ya) can occur anywhere in the body. It is described by its anatomical location, and examples include abdominal ischemia or the transient ischemic attack that can signal a stroke. Aides said Mr. Yeltsin's ischemia was caused by heart disease.

We have examined the differential binding of Hck and Fyn to HIV-1 Nef to elucidate the structural basis of SH3 binding affinity and specificity. Full-length Nef bound to Hck SH3 with the highest affinity reported for an SH3-mediated interaction (KD 250 nM). In contrast to Hck, affinity of the highly homologous Fyn SH3 for Nef was too weak (KD > 20 microM) to be accurately determined. We show that this distinct specificity lies in a variable loop, the 'RT loop', positioned close to conserved SH3 residues implicated in the binding of proline-rich (PxxP) motifs. A mutant Fyn SH3 with a single amino acid substitution (R96I) in its RT loop had an affinity (KD 380 nM) for Nef comparable with that of Hck SH3. Based on additional mutagenesis studies we propose that the selective recognition of Nef by Hck SH3 is determined by hydrophobic interactions involving an isoleucine residue in its RT loop. Although Nef contains a PxxP motif which is necessary for the interaction with Hck SH3, high affinity binding was only observed for intact Nef protein. The binding of a peptide containing the Nef PxxP motif showed > 300-fold weaker affinity for Hck SH3 than full-length Nef.

In aquatic animals, synthesis of the metal-binding protein metallothionein (MT) can be induced through exposure to elevated levels of metals in food or water. Whether the different routes of exposure lead to expression of different metallothionein isoforms in different tissues in unknown. In this study we examined the induction of metallothionein isoforms in the hepatopancreas and gills of the blue crab Callinectes sapidus. When blue crabs are exposed to cadmium in their diet, the metal accumulates in the hepatopancreas. Size-exclusion and anion-exchange chromatography show the presence of five low-molecular-mass cadmium-binding proteins. All of the observed cadmium-binding proteins belong to the class I MT family. They are designated as MT-Ia, MT-Ib, MT-Ic, MT-IIa and MT-IIb. All purified proteins run as single peaks upon rechromatography on anion-exchange HPLC, except for MT-Ic, which segregates into two peaks corresponding to MT-Ia and MT-Ic. The amino acid sequence of MT-Ia and MT-Ic is identical. MT-Ib differs from MT-Ia and MT-Ic only in having an extra N-terminal methionine. The 18 cysteine residues in MT-Ia and MT-IIa occur in identical positions; however, of the remaining 40 amino acids, 15 are found to be different. MT-IIb is identical with MT-IIa, except for an extra methionine residue at its N-terminal position. It appears therefore that, of the five observed CdMTs, only two are the products of distinct genes. CdMT-Ia and -IIa are posttranslationally modified forms of Ib and IIb, respectively, and CdMT-Ia and -Ic appear to be conformational isomers. Cadmium-induced expression of the two genes is tissue-specific. When crabs are exposed to cadmium in water, the metal accumulates in the gills, where it is bound to MT-II. MT-I is virtually absent

The Nobel awards were created by the will of Alfred Nobel, the Swedish chemist and inventor of dynamite. Yet the prize almost never came into being. The king of Sweden and the prime minister went to court to fight Nobel's will because they believed his wealth would be scattered around the world, to Sweden's loss

Responding to congressional criticism and a report by the National Academy of Sciences, HHS Secretary Donna E. Shalala said on Oct 12, 1995 that a top agency official was being designated as the government's blood-safety director. Philip R. Lee, assistant secretary for health, will have overall responsibility for the nation's blood supply when there is a serious danger of contamination

In a warning to eye doctors, federal health officials said Tuesday that patients who suffer bacterial infections after surgery to remove cataracts and implant lenses need treatment with antibiotics that are injected only into the eye and not systemically through a vein

The warning by the National Eye Institute applies to the estimated 5,400 patients who suffer bacterial eye infections each year after cataract surgery, a procedure that 1.35 million Americans undergo annually. Beyond sparing patients the discomfort of a second surgical eye procedure, health officials said that their recommendations, if fully implemented, would save at least $40 million a year in health costs by eliminating many hospital stays and intravenous antibiotics, which cost about $4,000 for each patient. The study's purpose was to determine the effectiveness of intravenous antibiotics as well as a surgical procedure to replace the gel-like filling inside the eye. Eye doctors have used the treatments for many years although their safety and effectiveness have not been determined in a scientifically controlled study. Patients whose vision initially was worse had much better visual results with vitrectomy than with the minor procedure. With vitrectomy, this group of patients was three times more likely to achieve 20/40 final vision (33 percent compared with 11), twice as likely to achieve 20/100 final vision (56 percent compared with 30) and less than one-half as likely to incur severe visual loss of less than 5/200 (20 percent compared with 47)

Edward B. Lewis, Eric F. Wieschaus and Christiane Nusslein-Volhard won the Nobel Prize in Physiology or Medicine on Oct 9, 1995 for discovering how genes control the early structural development of the body. All three studied the fruit fry to begin to unravel the secrets of how embryos develop from a single cell into well-differentiated anatomical structures like brains and legs. The research helps to explain birth defects in humans

Louis Pasteur, one of the legendary figures in the history of science, lied about his research, stole ideas from a competitor and was deceitful in ways that would now be regarded as scientific misconduct if not fraud, according to a revisionist history published this month. The Private Science of Louis Pasteur, by Dr. Gerald L. Geison of Princeton University, is based on an examination of Pasteur's 102 laboratory notebooks, which have been well preserved for more than a century. In 1881, after having helped to establish the germ theory of fermentation and disease, Pasteur turned to veterinary and human medicine. He tried to reduce the virulence of microbes by exposing them to oxygen in order to make them suitable for vaccination. But in developing a vaccine against anthrax, a bacterial infection that was economically important because it was a major killer of sheep, Pasteur adapted a method he had used a year earlier to produce a vaccine against chicken cholera. To head off competitors, Pasteur had purposely withheld reporting the simple method he used to prepare the chicken cholera vaccine

Summary: A study at Johns Hopkins University finds that people with the enervating ailment have a kind of hypotension A small study published in The Journal of the American Medical Association strongly links chronic fatigue syndrome to a common abnormality in the way the body regulates blood pressure