Structural features of growth factor receptors with oncogenic potential.
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Amino Acid Sequence↗
Biomedical subjects
D Smith
Publications and source records attributed to D Smith.
Roles of lab staff.
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Clinical Laboratory Techniques↗
Luteal phase serum progesterone levels after follicle aspiration with and without clomiphene citrate treatment.
Peripheral serum progesterone (P) levels were studied on random days after the spontaneous luteinizing hormone (LH) surge in women who underwent follicle aspiration. Comparisons were made with ovulatory women treated with clomiphene citrate (CC) undergoing follicle aspiration and women undergoing midcycle general anesthesia and laparoscopy without follicle aspiration. There were no differences in mean P levels in the group of women who underwent follicle aspiration, compared with the group who did not. Women treated with CC showed higher P levels during the first week of the luteal phase. During the second week of the luteal phase P levels were similar, regardless of follicle aspiration alone or in combination with CC use. In the groups not using CC, more individual women had P levels less than 10 ng/ml. Follicle aspiration does not appear to reduce luteal phase P levels in groups of patients in the natural menstrual cycle or receiving CC. Some individual patients, however, appear to be at risk for lower P levels, particularly after follicle aspiration or general anesthesia, in the natural cycle.
Clomiphene↗
Psychiatry. My day at the Henderson.
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Hospital Administration↗
Monoamine oxidase A and monoamine oxidase B activities are catalyzed by different proteins.
Monoamine oxidases A and B (amino: oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4) have been identified in the outer membranes of rat liver mitochondria by their covalent reaction with the inhibitor, [3H]pargyline. On analysis by polyacrylamide gel electrophoresis under denaturing conditions. Monoamine oxidase A was found to migrate more slowly that monoamine oxidase B. Proteins which correspond to monoamine oxidases A and B (as identified by the electrophoretic distribution of covalently bound [3H]pargyline) were excised from the gels. Subsequent analysis showed that both monoamine oxidase A and monoamine B had been highly purified by this procedure. Electrophoretic analysis of the peptides produced by limited proteolysis with bovine trypsin, alpha-chymotrypsin, Staphylococcus aureus V8 proteinase and cyanogen bromide indicate that monoamine oxidases A and B have different amino acid sequences.
Amino Acid Sequence↗
Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization.
Human Tumor Necrosis Factor and Lymphotoxin are cytotoxic proteins which have similar biological activities and share 30 percent amino acid homology. The single copy genes which encode these proteins share several structural features: each gene is approximately three kilobase pairs in length and is interrupted by three introns. In addition, these genes are closely linked and have been mapped to human chromosome 6. However, only the last exons of both genes, which code for more than 80 percent of each secreted protein, are significantly homologous (56 percent).
Amino Acid Sequence↗
Influence of the aortic component of the second heart sound on left ventricular maximal negative dP/dt in the dog.
Maximal negative left ventricular dP/dt is widely used as a measure of isovolumic muscular relaxation of the left ventricle. In the course of canine experiments designed to elucidate the hemodynamic events responsible for the aortic component of the second heart sound, high-fidelity left ventricular pressure and dP/dt signals were recorded and accelerations detected on the root of the aorta and epicardium at the cardiac apex. The second heart sound was coincident with maximal negative dP/dt and affected its magnitude to a variable and unpredictable extent. This may account for some of the unexpected variations in magnitude of maximal negative dP/dt that have been described in various disease states and in laboratory experiments where the effects of physiologic and pharmacologic interventions have been studied.
Animals↗
Freeze-fracture observations on mammalian oocytes.
Freeze-fracture studies on mammalian oocytes have been hampered by the relatively small numbers of cells available at a given time as well as by difficulties encountered in effectively freezing these large, watery cells. We have nevertheless pursued this area because of the benefits of visualizing membrane faces involved in various fusion reactions by the freeze-fracture method. Our observations indicate no overall change in intramembranous particle (IMP) distribution before and after sperm penetration, although the question of possible alterations of these structures at the precise locus of sperm attachment remains open. Preliminary statistical analysis indicates that there is a much higher IMP density on the P face than on the E face of the plasma membrane and that the microvillar membranes bear more IMPs than those of the intermicrovillus regions. Probes of lipid subclasses were used to determine the distribution of cholesterol and anionic lipid in the egg plasma membrane. Filipin and tomatin showed extensive complex formation in microvillus as well as nonmicrovillus regions, whereas anionic lipids (using polymyxin B) have been difficult to detect on the oocyte surface. These results are discussed relative to current views of membrane fusion mechanisms.
Animals↗
A randomised trial of tamoxifen versus tamoxifen with aminoglutethimide in post-menopausal women with advanced breast cancer.
Sixty-six post-menopausal women with metastatic breast cancer were randomised to receive tamoxifen or tamoxifen with aminoglutethimide. The women in the tamoxifen group were virtually free of toxicity, whilst 45% of patients in the aminoglutethimide group had toxicity and 13% discontinued the drug because of this. Responses were seen in 19% of patients receiving tamoxifen alone and 23% of those receiving both drugs. There is no indication that the increased toxicity seen with the addition of aminoglutethimide to tamoxifen in this situation is justified by an increased response rate.
Aged↗
The relationship of semen parameters to fertilization in patients participating in a program of in vitro fertilization.
Approximately 80% of the patients in a program of in vitro fertilization (IVF) will fertilize an oocyte. The purpose of this study was to determine which parameters of the semen analysis influence fertilization in vitro. Of 120 patients participating in an in vitro fertilization program, 98 achieved fertilization of at least one mature oocyte and 22 did not. Ovulation induction was standardized and patients whose sperm was exposed to at least one mature oocyte (by light microscopy) were included in the study. Semen washing was accomplished using a "swim-up" technique. Semen parameters were assessed both before (raw) and after washing. Following insemination with 100,000 motile sperm, fertilization was determined by the presence of pronuclei or cleavage. Mean sperm count and motility were higher in patients who fertilized. However, morphology was similar. Fertilization was more likely to occur with a raw density greater than 104 million/ml and a motility greater than 64%, as well as with a density greater than 18 million/ml and a motility greater than 86% following washing. Furthermore, washing lowered sperm counts by 75% and increased motility by 25% but had no effect on morphology. This study demonstrates that sperm count and motility, but not morphology, influence fertilization in a program of in vitro fertilization and that patients with higher counts and motility have a greater probability of fertilization.
Female↗
Hepatic and peripheral insulin resistance following streptozotocin-induced insulin deficiency in the dog.
Insulin resistance and insulin deficiency are both present in many patients with diabetes mellitus. We tested the hypothesis that insulin resistance can evolve from a primary lesion of the beta-cell secretory function. Insulin-mediated glucose uptake (insulin clamp), endogenous glucose production, and glucose-stimulated insulin secretion (hyperglycemic clamp) were measured in awake dogs before and four to six weeks after streptozotocin-induced diabetes mellitus. Streptozotocin (30 mg/kg) resulted in a significant rise in the mean fasting plasma glucose concentration from 104 +/- 2 mg/100 mL to 200 +/- 34 mg/100 mL, (P less than 0.05), and a slight decrease in the mean fasting plasma insulin concentration (from 21 +/- 2 microU/mL to 15 +/- 2 microU/mL). Under conditions of steady-state hyperglycemia (+75 mg/100 mL hyperglycemic clamp, insulin secretion was reduced by 75% in the streptozotocin-treated dogs (P less than 0.025), and the total amount of glucose metabolized decreased from 13.56 +/- 1.04 to 4.74 +/- 0.70 mg/min X kg (P less than 0.001). In the postabsorptive state, endogenous glucose production was slightly, although not significantly, higher in the diabetic dogs (3.05 +/- 0.46 v 2.51 +/- 0.22 mg/min . kg), while the glucose clearance rate was 35% lower (P less than 0.001). When the plasma insulin concentration was increased to approximately 45 microU/mL (insulin clamp) while holding plasma glucose constant at the respective fasting levels (99 +/- 1 and 186 +/- 30 mg/100 mL), endogenous glucose production was completely suppressed in control dogs but suppressed by only 51% (1.46 +/- 0.37 mg/min . kg, P less than 0.025) in diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Does infection with environmental mycobacteria suppress the protective response to subsequent vaccination with BCG?
Using a guinea pig model of experimental airborne tuberculosis, we were unable to find evidence to support the hypothesis that infection with environmental mycobacteria (M. simiae or M. avium-intracellulare) interferes with the induction of a protective response in animals subsequently vaccinated with BCG.
Animals↗
Ovulation induction in polycystic ovary syndrome with urinary follicle-stimulating hormone or human menopausal gonadotropin.
In patients with polycystic ovarian disease (PCOD) ovulation was induced with a combination of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or with urinary follicle-stimulating hormone (uFSH; Metrodin, Serono Laboratories, Inc., Randolph, MA) alone. hMG/hCG and uFSH resulted in comparable rates of ovulation and conception in patients with PCOD. The incidence of hyperstimulation and the potential for multiple births appeared lower with uFSH. The fact that endogenous ovulation did not occur in hMG patients who had hCG withheld or in 3 of the 11 uFSH patients who had preovulatory levels of estradiol and follicles greater than 15 mm may imply that these similarly derived gonadotropins in some instances block endogenous ovulation.
Androstenedione↗
Teratoma of the umbilical cord.
A case of teratoma of the umbilical cord is described. Four previous reports of this entity are briefly reviewed, and a detailed description of the current case is presented. The histogenesis of teratomas at this unusual site is discussed. The features that distinguish teratomas of the umbilical cord and placenta from acardius fetus are enumerated.
Adult↗
Origin of the third heart sound: comparison of ventricular wall dynamics in hyperdynamic and hypodynamic types.
To investigate the left ventricular wall dynamics conducive to the third heart sound (S3) in both hyper- and hypodynamic filling conditions, eight dogs were studied in which an S3 was produced by hypoxemia and in eight others by acute mitral regurgitation. Pulse transit sonomicrometry crystals were used to measure external left ventricular dimension dynamics in the two principal axes. A miniature accelerometer was used to detect the epicardial S3 vibration. The development of the S3 was invariably associated with an increased peak velocity of long-axis external dimensional expansion in early diastole. This enhanced long-axis filling activity was not dependent on increased global chamber or short-axis filling dynamics and sometimes occurred when global filling rate was unchanged. In addition, the short-axis filling rate was sometimes reduced as the S3 developed. It is concluded that the common denominator of S3 generation in this acute dog model is exaggerated long-axis diastolic expansion activity which is present in both hyper- and hypodynamic left ventricular filling.
Acute Disease↗
Amino acid sequence of the alpha subunit of transducin deduced from the cDNA sequence.
Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes Gs and Gi, the regulatory proteins of adenylate cyclase. Here we report the cDNA sequence and deduced amino acid sequence of transducin's alpha subunit (T alpha). The cDNA was isolated, by screening with an antibody probe, from a bovine retinal cDNA library in the expression vector lambda gt11. The 2.2-kilobase cDNA insert hybridized to a single 2.6-kilobase poly(A)+ RNA species present in extracts of bovine retina but not of bovine heart, liver, or brain. The nucleotide sequence of the cDNA revealed an open reading frame long enough to encode the entire 39-kDa T alpha polypeptide. The polypeptide sequence deduced from the cDNA would be composed of 350 amino acids and have a molecular weight of 39,971. Portions of the sequence matched reported amino acid sequences of T alpha tryptic fragments, including sites specifically ADP-ribosylated by cholera and pertussis toxins. The predicted sequence also includes four segments, ranging from 11 to 19 residues in length, that exhibit significant homology to sequences of GTP-binding proteins, including the ras proteins of man and yeast and the elongation factors of ribosomal protein synthesis in bacteria, EF-G and EF-Tu. In combination with previous functional studies of tryptic fragments of T alpha, the deduced amino acid sequence makes it possible to predict which portions of the polypeptide interact with other molecules involved in retinal phototransduction.
Amino Acid Sequence↗
Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady-state analysis of the work/energy cost transfer function.
The concept of transfer function for organ performance (work output vs. biochemical input) is developed for skeletal and cardiac muscle under steady-state exercise conditions. For metabolic control by the ADP concentration, the transfer function approximates a Michaelis-Menten hyperbola. Variation of the work identifies metabolic operating points on the transfer function corresponding to ADP concentrations or to a ratio of inorganic phosphate to phosphocreatine that can be determined by phosphorus nuclear magnetic resonance. This operating point is characterized by the fraction (V/Vmax) of maximal activity of oxidative metabolism in the steady state. This quantity appears to be useful in predicting the degree to which metabolic homeostasis is effective; poorly controlled metabolic states can readily be identified and are used in the diagnosis and therapy of metabolic disease in the organs of neonates and adults.
Adenosine Diphosphate↗
Altered fidelity of mitotic chromosome transmission in cell cycle mutants of S. cerevisiae.
Thirteen of 14 temperature-sensitive mutants deficient in successive steps of mitotic chromosome transmission (cdc2, 4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17 and 20) from spindle pole body separation to a late stage of nuclear division exhibited a dramatic increase in the frequency of chromosome loss and/or mitotic recombination when they were grown at their maximum permissive temperatures. The increase in chromosome loss and/or recombination is likely to be due to the deficiency of functional gene product rather than to an aberrant function of the mutant gene product since the mutant alleles are, with one exception, recessive to the wild-type allele for this phenotype. The generality of this result suggests that a delay in almost any stage of chromosome replication or segregation leads to a decrease in the fidelity of mitotic chromosome transmission. In contrast, temperature-sensitive mutants defective in the control step of the cell cycle (cdc28), in cytokinesis (cdc3) or in protein synthesis (ils1) did not exhibit increased recombination or chromosome loss.--Based upon previous results with mutants and DNA-damaging agents in a variety of organisms, we suggest that the induction of mitotic recombination in certain mutants is due to the action of a repair pathway upon nicks or gaps left in the DNA. This interpretation is supported by the fact that the induced recombination is dependent upon the RAD52 gene product, as essential component in the recombinogenic DNA repair pathway. Gene products whose deficiency leads to induced recombination are, therefore, strong candidates for proteins that function in DNA metabolism. Among the mutants that induce recombination are those known to be defective in some aspect of DNA replication (cdc2, 6, 8, 9) as well as some mutants defective in the G2 (cdc13 and 17) and M (cdc5 and 14) phases of the mitotic cycle. We suggest that special aspects of DNA metabolism may be occurring in G2 and M in order to prepare the chromosomes for proper segregation.
Cell Cycle↗