Conformational flexibility in a small globular hormone: x-ray analysis of avian pancreatic polypeptide at 0.98-A resolution.
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Biomedical subjects
Publications and source records attributed to S Wood.
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The physiological integrity of the in situ perfused heart of the ocean pout was established by its ability to maintain cardiac output (Q) over a range of work loads, and by the dependence of Q upon the filling pressure of the heart. Similar observations have been reported previously for the in situ perfused heart of the sea raven. Physiological levels of extracellular acidosis (pH 7.6/1% CO2 and pH 7.4/2% CO2) significantly depressed cardiac performance in sea raven and ocean pout hearts in situ. Negative chronotropic and inotropic responses were observed. Adrenaline (AD; 10(-7) M) under control conditions (pH 7.9/0.5% CO2) produced a sustained tachycardia. The tachycardia reduced filling time of the ventricle and stroke volume was compromised because of the constant preload to the heart. Consequently, AD produced only an initial, transient increase in stroke volume and Q. Thereafter, stroke volume was reduced in proportion with the increase in heart rate, and Q remained unchanged. The combined challenge of extracellular acidosis and AD demonstrated interactive effects between AD and acidosis in situ. Q and power output were maintained in both species at both levels of extracellular acidosis during the combined challenge. Thus AD alone can maintain (but not improve upon) basal Q during extracellular acidosis. The effects of extracellular acidosis, circulating catecholamines and venous return pressure to the heart are discussed in relation to the regulation of Q following exhaustive exercise.
Pentachlorophenol (PCP) is a pesticide commonly used as a wood preservative. Although exposure has been well controlled in large chemical manufacturing plants, over-exposures have recently becomes a concern at smaller facilities. Five cases of PCP poisoning, including two fatalities, occurred in two small wood preservative plants. All cases presented with fever, including severe hyperpyrexia in two; an increased anion gap and renal insufficiency were noted in two others. PCP may uncouple oxidative phosphorylation, resulting in a poisoning syndrome characterized by hyperpyrexia, diaphoresis, tachycardia, tachypnea, abdominal pain, nausea, and even death.
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There has been recent speculation about the role of hydrogen bonding in molecular mechanisms of anaesthesia. We have tested this hypothesis by comparing the potencies of chloroform and deuterated chloroform in mice, using loss of righting reflex as the endpoint for anaesthesia. We found that the ED50 for chloroform was 0.297 +/- 0.03% (SD) and for deuterated chloroform 0.318 +/- 0.02% (SD). These values are not significantly different. However, there were some differences in toxicity with deuterated chloroform having less "acute" toxicity. This is compatible with an isotope effect in which deuterium interferes with the formation of reactive free radicals. We conclude from the potency data that hydrogen bonding can be excluded as the major mechanism of chloroform anaesthesia.
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Purified type 1 somatic pili from enterotoxigenic Escherichia coli (ETEC) strain H10407 (O78:H11) was evaluated as a parenteral immunizing agent in the hope that this antigen might enhance a contemplated polyvalent pilus vaccine. Intramuscular inoculation with 45, 90, 900 or 1 800 mcg of pili vaccine was tolerated without incident in 82 volunteers. Six of 15 persons who received a 28 day booster of 1 800 mcg developed local reactions while none of 52 persons receiving 180 or 450 mcg boosters evinced such reactions. Pili vaccine did not significantly alter intestinal transit time, absorptive capacity or the prevalence of colonic E. coli bearing type 1 somatic pili of the H10407 antigenic variety. All vaccinees developed significant rises in circulating IgG antibody to type 1 somatic pili, the magnitude of the response being directly proportioned to the vaccine dose. None of the vaccinees had significant rises to CFA I or II pili nor to heat-labile enterotoxin. However, many had rises in O antibody, particularly among those inoculated with 1 800 mcg. Three challenge studies were carried out with E. coli H10407 to assess vaccine efficacy. In the initial study the vaccinees were either protected against diarrhea (2 of 6 vaccinees versus 7/7 of controls) or had milder disease than the controls. In two subsequent challenges with H10407 significant protection was not seen. It was not clear whether protection exhibited by the vaccinee group in the first challenge was due to O antibody, pili antibody, or both acting synergistically. To clarify this, a group of the immunized volunteers were challenged with ETEC strain B7A which is a different serotype (O148:H28) lacks CFA/I or II pili, but possesses type 1 somatic pili antigenically distantly related to those of H10407. Attack rates and severity of illness were similar in both vaccinee and control groups. While most volunteers challenged with E. coli H10407 developed significant rises in circulating antibody to CFA/I, LT and O antigen, none had rises to type 1 somatic pili. It is unclear if this is due to immune tolerance to this antigen when encountered enterally or whether these pili are not present in vivo in ETEC initiating diarrhea in the proximal small intestine. In summary, parenterally inoculated type 1 somatic pili were safe and highly immunogenic in man but did not consistently induce protection. Further studies are planned to clarify the role of antibody to type 1 somatic pili in mediating protection.
A gonococcal pilus vaccine or placebo was injected subcutaneously or intramuscularly into 71 human volunteers. The vaccine was found to be safe. The principal adverse reaction was a complaint of a sore arm, which was caused, at least in part, to the volume of material injected. 6 of 64 (9%) volunteers receiving the larger doses also complained of malaise. The vaccine was found to be antigenic. All of the volunteers developed an immunoglobulin class-specific antibody response as measured by a solid phase radioimmunoassay. The antibody was capable of blocking the attachment of gonococci to epithelial cells. A slight antibody response was also demonstrated to gonococcal lipopolysaccharide but the antibody responsible for blocking attachment of gonococci was directed entirely at the pilus protein. The stimulated antibodies were shown to crossreact with isolated pili of heterologous gonococcal strains and to block the attachment of heterologous gonococci. Absorption of immune sera by a heterologous pilus reduced the inhibition of attachment antibodies to pre-immune level, suggesting that the immune response was directed at a common pilus determinant.
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Fetal movements were directly visualized with a real-time ultrasound unit, and they were recorded after the random intravenous administration of either glucose or saline solution to the mother. A significant increase in fetal activity was seen 1 hour after the administration of glucose.
Serum alpha-L-fucosidase was assayed in 422 individuals. Extremely low levels of enzyme activity were found in 26 individuals. This variant enzyme has increased heat lability. The remaining samples exhibited a bimodal frequency distribution. Family studies suggest that the variant is inherited as a Mendelian recessive character. The variant leukocyte enzyme exhibits normal activity yet increased heat lability. Serum and leukocyte samples from individuals who do not possess the low activity variant are heterogeneous with respect to the heat lability of alpha-L-fucosidase. This common polymorphism may be useful for mapping purposes in family studies.
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Juvenile Sandhoff, Sandhoff, and Tay-Sachs fibroblasts were mixed in paired combinations and treated with polyethylene glycol (PEG) to promote cell fusion. The hexosaminidase (hex) isozymes of PEG-treated mixed-cell cultures were determined and compared with those of untreated control cultures. Fusions involving juvenile Sandhoff and Sandhoff fibroblasts did not show an increase in either total hexosaminidase or heat-stable hex B. Fusions of juvenile Sandhoff (or Sandhoff) and Tay-Sachs fibroblasts showed an increase of heat-labile hex A. Thus, juvenile Sandhoff cells show complementation with Tay-Sachs cells but not Sandhoff cells. Consequently, the genetic defect in juvenile Sandhoff disease probably represents an allelic mutation of the gene that is defective in Sandhoff disease.
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