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Biomedical subjects

E Chen

Publications and source records attributed to E Chen.

At least 199 records · Page 11Linked to original sources
PubMed1992

Measured enthusiasm: does the method of reporting trial results alter perceptions of therapeutic effectiveness?

OBJECTIVE: To compare clinicians' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome. DESIGN: Survey, with random allocation of two questionnaires. SETTING: Toronto teaching hospitals. RESPONDENTS: Convenience sample of 100 faculty and housestaff in internal medicine and family medicine. INTERVENTION: One questionnaire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events; the other showed the same end points as relative differences. Both questionnaires included a fourth "trial," showing person-years of treatment needed to prevent one myocardial infarction. MAIN OUTCOME MEASURE: The "trials" were each rated on an 11-point scale, from treatment "harmful" to "very effective." RESULTS: Respondents' ratings of effectiveness varied with the end point. Controlling for end point, ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions (P < 0.001); however, no end-point difference was more than 0.6 scale points. For a "trial" reporting that 77 persons were treated for 5 years to prevent one myocardial infarction, mean ratings were 2.3 or 1.8 scale points lower, respectively (both P < 0.001), than when the same data were shown as relative or absolute risk reductions. CONCLUSIONS: Clinicians' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements, by end-point emphasis, and, above all, by underuse of summary measures that relate treatment burden to therapeutic yields in a clinically relevant manner.

Adult↗
PubMed1992

Extended x-ray absorption fine structure studies of a retrovirus: equine infectious anemia virus cysteine arrays are coordinated to zinc.

Zinc finger arrays have been established as a critical structural feature of proteins involved in DNA recognition. Retroviral nucleocapsid proteins, which are involved in the binding of viral RNA, contain conserved cysteine-rich arrays that have been suggested to coordinate zinc. We provide metalloprotein structural data from an intact virus preparation that validate this hypothesis. Extended x-ray absorption fine structure (EXAFS) spectroscopy of well-characterized and active preparations of equine infectious anemia virus, compared with a peptide with known coordination and in combination with available biochemical and genetic data, defines a Cys3His1 coordination environment for zinc. The average of the Zn-S distances is 2.30(1) A and that of the Zn-N distance (to histidine) is 2.01(3) A.

Absorptiometry, Photon↗
PubMed1992

A randomized study of the systemic effects of warm heart surgery.

The technique of warm heart surgery is defined as continuous warm blood cardioplegia and normothermic cardiopulmonary bypass. Although the systemic effects of traditional myocardial protection are well known, the effects of warm heart surgery are not. In a prospective trial, 204 patients undergoing coronary artery bypass grafting were randomized to the warm heart surgery technique (normothermic group) or traditional intermittent cold blood cardioplegia and cardiopulmonary bypass (hypothermic group). The groups had similar heparin sodium requirement, activated clotting times, urine output, hematocrit, and blood product utilization. There were no differences in hemodynamics immediately after cardiopulmonary bypass. The normothermic patients had a higher incidence of spontaneous defibrillation at cross-clamp removal (84%) than the hypothermic patients (33%) (p less than 0.01). An increase in the flow rate of low K+ cardioplegia was necessary to eradicate electrical activity during aortic occlusion more often in the normothermic patients (20%) than in the hypothermic patients (3%) (p less than 0.01). When low K+ cardioplegia was ineffective, high K+ cardioplegia was necessary to eradicate electrical activity in 31% of the normothermic patients compared with 10% of the hypothermic patients (p less than 0.05). The total cardioplegia volume delivered to the normothermic group (4.7 +/- 1.9 L) was higher than that delivered to the hypothermic group (2.6 +/- 0.8 L) (p less than 0.01). Although urine output was similar in both groups, the serum K+ levels were higher in the normothermic group (5.7 +/- 0.8 mmol/L) than in the hypothermic group (5.3 +/- 0.8 mmol/L) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Cytochrome oxidase activity in rat retina after exposure to 404 nm blue light.

Cytochrome oxidase (CYO), a key enzyme in the respiratory chain, was observed as an indicator of retinal metabolism after an in vivo blue light exposure. Thirty Sprague-Dawley rats were exposed to optic radiation of 404 nm with a retinal dose of 110kJ/m2. Immediately after exposure, the CYO activity in the pigment epithelium, in the outer and inner segments of photoreceptors, and in the outer plexiform layer of the exposed retina, was reduced to one-third-to-half of the control level. However, there was an increase in CYO activity in the exposed retina one day after exposure. One week after exposure, the CYO activity in the inner segment and the outer plexiform layer was higher, while the activity in the other two layers was lower, than that at one day, although still higher than in the control. Two weeks after exposure, the CYO activity in the four retinal layers returned to the level of the control retina, as did the activity four weeks after. After exposure, no ophthalmoscopically visible retinal change and no light-microscopically evident morphological alterations were found. There was no retinal edema or loss of photoreceptor cells. The observed alteration in CYO activity after blue light exposure may represent an inhibition of retinal metabolism. The inhibition was reversible. If this compensation mechanism is overwhelmed, retinal damage may occur.

Animals↗
PubMed1991

Two commonly occurring nucleotide base substitutions in Chinese G6PD variants.

Using a direct PCR sequencing technique, we have identified two DNA base substitutions in 8 different biochemical G6PD variants of Chinese origin. Neither one of these abnormalities has been reported in other ethnic groups. An abnormality (C1) of G to T substitution at cDNA 1376 causing an amino acid change from Arg to Leu has been found in 3 variants. Another abnormality (C2) of G to A substitution at cDNA 1388 causing an amino acid change from Arg to His has been found in 5 variants. Both C1 and C2 are located in exon 12 of the G6PD gene and are only 12 base pairs apart. However, C1 is associated with a significant increase in the deamino-NADP utilization rate, whereas C2 is not. Taken together, our data suggest that C1 and C2 are very common among Chinese with a G6PD deficiency and exon 12 may define an important functional domain of the human G6PD.

Base Sequence↗
PubMed1991

Cell-type specificity of interferon-gamma-mediated HLA class I gene transcription in human hematopoietic tumor cells.

Major histocompatibility complex class I gene expression plays a central role in cellular immunity and tumor surveillance. A substantial proportion of spontaneous tumors are class I-deficient and numerous experiments have suggested that alterations in class I expression may alter oncogenicity and, as a result, have potential therapeutic impact. Interferons (IFNs) are able to upregulate class I expression by mechanisms that remain to be elucidated, but which appear to be IFN- and cell-type specific. We have characterized in detail the in vivo class I transcriptional response to IFN-gamma in two human hematopoietic tumor cell lines, the class I-deficient K562 cell line and the class I-positive Ramos cell line. In each, IFN-gamma induces a rapid increase in class I transcription, which is sustained in Ramos cells, but transient in K562 cells. In each, stimulation by IFN-gamma is dependent on ongoing protein synthesis, suggesting the requirement for production of a "primary response" protein. These data suggest that more than one type of IFN-gamma-induced signal is operative in the transcriptional response to IFN-gamma. Cycloheximide alone is also capable of inducing a rapid increase in class I transcription in both cell types, suggesting that constitutive attenuation of class I transcription may be a common phenomenon, and that IFN-gamma may act, in part, by interfering with such attenuation.

Antibodies, Monoclonal↗
PubMed1991

Identification of structural markers for vitamin B12 and other corrinoid derivatives in solution using FTIR spectroscopy.

The identification of structural markers for B12/protein interactions is crucial to a complete understanding of vitamin B12 transport and metabolic reaction mechanisms of B12 coenzymes. Fourier transform infrared spectroscopy can provide direct measurements of changes in the side chains and corrin ring resulting from B12/protein interactions. Using FTIR spectroscopy in various solvent systems, we have identified structural markers for corrinoids in the physiological state. We assign the major band (denoted B), which occurs at ca. 1630 cm-1 in D2O and ca. 1675 cm-1 in ethanol, to the amide I C=O stretching mode of the propionamide side chains of the corrin ring. The lower frequency of band B in D2O versus ethanol is due to the greater hydrogen-bonding properties of D2O that stabilize the charged amide resonance form. Since the propionamides are known to be important in protein binding, band B is a suitable marker for monitoring the interaction of these side chains with proteins. We assign bands at ca. 1575 and 1545 cm-1 (denoted C and D) as breathing modes of the corrin ring on the basis of the bands' solvent independence and their sensitivity to changes in axial ligation. As the sigma-donating strength of the axial ligands increases, the frequencies of bands C and D decrease, possibly indicating a lengthening of the corrin conjugated system. Band A, the known cyanide stretching frequency at ca. 2130 cm-1, probes the cobalt-carbon distance in cyanocorrinoids. As the frequency of band A increases, the cobalt-carbon bond strength should decrease.

Amides↗
PubMed1991

A group of interacting yeast DNA replication genes.

Mutations in the cell-division-cycle genes CDC46 and CDC47 were originally isolated as suppressors of mutations in two other cell-division-cycle genes (CDC45 and CDC54). We found several combinations of mutations in these genes that result in allele-specific suppression and synthetic lethality, confirming that this set of genes forms a group of genetically interacting components. Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis. Mutants defective in each of the four genes exhibit high rates of mitotic chromosome loss and recombination. The mutants appear also to accumulate chromosome damage that can be detected by a novel chromosome electrophoresis assay. Conditional mutants in this group, under fully nonpermissive conditions, show cell-cycle arrest at the beginning of DNA synthesis; under less stringent conditions, some arrest later, in S-phase. The DNA sequence of the CDC46 gene indicates that the protein is a member of a new family of genes apparently required for DNA initiation, with family members now identified in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and mouse cells.

Alleles↗
PubMed1991

Selection, expression, and nucleotide sequencing of the glutamate dehydrogenase gene of Peptostreptococcus asaccharolyticus.

The gene for the catabolic NAD-linked glutamate dehydrogenase of Peptostreptococcus asaccharolyticus was cloned by selection of Escherichia coli for complementation of a biosynthetic defect. Cloned fragments containing the gene and the P. asaccharolyticus transcription and translation signals are very highly expressed in E. coli. The nucleotide sequence of the cloned gene was determined. It codes for a polypeptide of 421 amino acids, the sequence of which is similar to those of the NADP-accepting glutamate dehydrogenases. The sequence similarity of this protein to the mammalian glutamate dehydrogenases, which accept both NADP and NAD, is greater than its similarity to the bacterial NADP-specific dehydrogenases, suggesting that this NAD-specific bacterial glutamate dehydrogenase and the NADP-specific bacterial dehydrogenases diverged separately from the line leading to the dual-specificity mammalian glutamate dehydrogenases.

Amino Acid Sequence↗
PubMed1991

Lipid and protein density in the rat retina: a microradiographical study.

Lipid and protein density in each retinal layer were determined microradiographically in retinal sections of 10 rats. Lipid in retinal sections was extracted with chloroform. The fraction of dry mass remaining after lipid extraction is mainly protein. The dry mass lost in chloroform processing was calculated to obtain the lipid density, which accounts for about 30% of the total dry mass density. The total dry mass density in each retinal layer is the sum of the lipid and protein density. Lipid should be regarded as an important X-ray absorber when determining the dry mass density in the rat retina with microradiography.

Animals↗
PubMed1990

Nanosecond transient absorption spectroscopy of coenzyme B12. Quantum yields and spectral dynamics.

Photolysis of adenosylcobalamin leads to homolytic cleavage, similar to many of the B12-dependent enzyme reactions. Therefore, we have used photolysis to study the structure and lability of the cobalt-carbon bond. The nanosecond quantum yield for adenosylcobalamin is 0.23 +/- 0.04, higher than reported previously. The acidified form of adenosylcobalamin, so called "base-off" B12, has a much lower quantum yield at 0.045 +/- 0.015, demonstrating an inverse correlation between cobalt-carbon bond strength and quantum yield. Investigation of the wavelength dependence of the quantum yield shows that there is a highly efficient transmission of energy from the corrin ring to the cobalt-carbon bond. A comparison of nanosecond transient and static spectra showed small spectral differences. Therefore, any spectral relaxation of a sterically distorted corrin ring may be detectable only at sub-nanosecond timescales. Spectral analysis also provides data on the kinetics of recombination. In the absence of enzyme, geminate rebinding must be substantial, since the rate of Co(II) and deoxyadenosyl radical recombination is near the diffusion controlled limit. Therefore, it is likely that the enzyme functions to pull the geminate partners apart, perhaps as suggested previously, through a conformational change. The importance of geminate recombination in the mechanism of homolytic cleavage is further supported by a comparison of our results with picosecond transient absorption studies.

Cobamides↗
PubMed1990

Death takes a ride. Alcohol-associated single vehicle fatalities revisited.

Records from the Medical Examiner's Office of Westchester County (1980 population = 866,599) were studied for trends in blood alcohol levels in drivers who died after single vehicle accidents. Findings for all motorists (N = 102) who died in the earliest available eight-year period, 1952-1959, were compared with findings for all motorists (N = 183) who died from 1980 to 1987. The mean age of subjects in the two periods did not differ (37.3 yr +/- 15.4 SD versus 35.4 yr +/- 16.8 SD), and mean blood alcohol levels were nearly identical (0.14% +/- 0.12 SD) versus 0.13% +/- 0.12 SD). Based on the increase in vehicular miles travelled during the two periods, there may have been a 20-25% reduction in alcohol-associated mortality over a 30-year period. Following legislation raising the minimum drinking age to 21, no fatally injured drivers 20 years of age or under have had blood alcohol levels greater than or equal to 0.10%.

Accidents, Traffic↗
PubMed1989

Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases.

Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.

Amino Acid Sequence↗
PubMed1989

A fusion protein required for vesicle-mediated transport in both mammalian cells and yeast.

A protein sensitive to N-ethylmaleimide catalyses the fusion of transport vesicles with Golgi cisternae in a mammalian cell-free system. By cloning and sequencing its gene from Chinese hamster ovary cells and by use of in vitro assays, we show that this fusion protein is equivalent to the SEC18 gene product of the yeast Saccharomyces cerevisiae, known to be essential for vesicle-mediated transport from the endoplasmic reticulum to the Golgi apparatus. The mechanism of vesicular fusion is thus highly conserved, both between species and at different stages of transport.

Amino Acid Sequence↗