Importance of sample size for statistical significance.
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Biomedical subjects
Publications and source records attributed to M Young.
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Fifty-nine patients who underwent cryotherapy on the uterine cervix at University Hospital of Jacksonville between September 1974 and September 1980 subsequently gave birth at that institution. Of these patients, three had repeat cesarean sections and three had D&Cs in the interval between cryotherapy and pregnancy. The remaining 53 patients were matched with 53 controls for age, parity, fetal weight and absence of cervical surgery. Data were gathered and compared with respect to the cesarean section rate, precipitous dilation, cervical lacerations, postpartum hemorrhage, oxytocin augmentation of labor, Apgar scores, use of forceps and other obstetric complications. There were no significant differences in any of these parameters between the two groups. However, 19 cases had precipitous labor as opposed to 11 controls (0.1 greater than p greater than 0.05). Cryotherapy for cervical dysplasia does not appear to have any deleterious effects on the outcome of term labor.
As part of an examination of procedures for protein/lipid reconstitution we incubated solubilized cytochrome oxidase at different temperatures with preformed vesicles composed of saturated lipids. We observed that the 22Na permeability of these vesicles was increased following such an incubation step, with the maximal effect occurring following incubations at temperatures in the vicinity of the lipid gel to liquid-crystal phase change. However, these permeability changes could be completely duplicated by incubating similar vesicles with concentrations of Tween 80 used to solubilize the extracted oxidase. Thus detergent molecules used to solubilize extracted membrane proteins can induce significant changes in the reconstituting lipid environment and the possibility of such changes must be taken into account when interpreting the properties of the reconstituted lipid/protein system under study.
The formyl-methenyl-methylenetetrahydrofolate synthetase from chicken liver catalyzes the formation of the 10-formyl- and 5,10-methenyltetrahydrofolate cofactors via three enzymatic activities. In this report we define the kinetic relationships between the activities of this trifunctional protein. An investigation of the time course for 10-formyl cofactor synthesis by computer modeling indicates that commencing with tetrahydropteroyltriglutamate, the activities of the synthetase/cyclohydrolase couple act as separate enzymic species. In contrast, 10-formyl cofactor formation from the 5,10-methylene cofactor utilizing the dehydrogenase/cyclohydrolase couple is described by a single or interactive site model that partitions the 5,10-methenyl intermediate primarily (85%) to the 10-formyl product. An unusual characteristic of the latter coupled activities is the negligible cyclohydrolase activity toward exogenous 5,10-methenyl cofactor, which serves as substrate in the individual activity assay. This is based on (1) competitive inhibition by 5,11-methenyltetrahydrohomofolate against the 5,10-methenyl derivative in the cyclohydrolase-catalyzed hydrolysis but the absence of such inhibition in the dehydrogenase/cyclohydrolase couple and (2) a pulse-chase experiment showing the failure of chase 5,10-methenyl cofactor to dilute the 10-formyl product derived from the coupled activities. The result of this coupling is to minimize the concentration of the 5,10-methenyl species, consistent with its noninvolvement in de novo purine biosynthesis.
The relationship between placental protein synthesis and transfer of amino acids from mother to foetus was studied in the guinea pig, by using [U-14C]-lysine, -leucine, -glycine, -aspartate and -alpha-aminoisobutyrate. The uptake of label by protein was 12-16% of total label transferred. Cycloheximide inhibited incorporation of all naturally occurring amino acids into protein by 81-96% and transfer by 62-75%; the concentration of label in the free pool was increased for each. These findings were confirmed when specific-radioactivity measurements were made with L-[U-14C]lysine. The transfer of the non-protein amino acid alpha-aminoisobutyrate was not significantly decreased by cycloheximide. A model, linking protein synthesis to the generation of a transfer pool of amino acids, is proposed whereby inhibition of protein synthesis decreases the amount of amino acid available for transfer.
Topical application of mouse nerve growth factor (NGF) to superficial skin wounds of mice has previously been shown to accelerate the rate of wound contraction. Results of the present study reveal that NGF in the presence of plasma is also chemotactic for human polymorphonuclear leukocytes in vitro, and the concentration of NGF required for this effect is similar to that which stimulates ganglionic neurite outgrowth. This property does not arise from liberation of the C5a fragment of complement, nor does it require the known enzymic activity of NGF. (NGF inactivated with diisopropyl fluorophosphate is equally active.) We conclude that NGF can display biological effects on cells of nonneural origin and function, and this feature might play a role in the early inflammatory response to injury.
An Escherichia coli plasmid, p1949, that is derived from pMB9 and pC194, and unable to replicate in Bacillus subtilis, can give rise to stable CmR transformants of the latter species if it is inserted into the bacterial chromosome. A purified segment of the B. subtilis chromosome, with transforming activity against pheA1 and nic-38 recipients, was used to direct the insertion of p1949 into the B. subtilis chromosome. Insertion of the ligated DNA segments occurred in the region of the chromosome from which the purified phe-nic segment was derived. Many of the properties of the resulting CmR transformants of B. subtilis are consistent with the occurrence of a Campbell recombination mechanism leading to integration. However, certain of these properties are more easily explained if it is proposed that integration occurs by a reciprocal recombination event involving a linear ligation product. Evidence is presented suggesting that the inserted sequences may be tandemly duplicated. This may effectively vitiate the use of p1949 as a convenient means for complementation analysis of recessive mutations in B. subtilis.
The influence of fetal plasma substrate and insulin concentrations on the fractional synthesis rate or turnover of the mixed proteins in the organs of fetal lambs was calculated from measurements of the rate of uptake of L-14C lysine by the protein in the steady state in utero. The control values for protein synthesis rate in the fetal organs of Welsh mountain ewes, 130 to 140 days' pregnant, were similar to those previously observed in the fetuses of Border Leicester ewes: the mean turnover rates were 38, 72, 40 and 63 per cent per day for the brain, liver, cardiac muscle and the placenta respectively; that for skeletal muscles was 6.8 per cent per day; the corresponding half lives were 2.15, 1.27, 1.8 and 1.42 days respectively and 11.3 days for skeletal muscle. A fivefold increase in the plasma glucose levels had no influence on protein turnover rate over a six hour period. A fourfold increase in the concentration of some amino acids, following a mixed infusion, decreased turnover rate in brain, heart and liver. The half life was increased by 30 per cent, but a small reduction in half life was observed in skeletal muscle. Insulin caused a fall in intracellular lysine concentration in skeletal muscle and in plasma, which suggests that the hormone can reduce muscle protein catabolism in the fetal lamb in the last trimester of gestation. Enhancement of synthesis rate occurred in the presence of the amino acid infusions only; the half life of the proteins was reduced by a factor of three. Insulin also increased placental protein synthesis rate by 50 per cent but had no influence on the other tissues studied.
Coronary vascular interactions between adenosine and the calcium entry blocker, nifedipine were studied in the open-chest, blood-perfused dog heart. Adenosine was administered either as a constant intra-coronary infusion or released endogenously during brief occlusions of the left anterior descending (LAD) coronary artery. Nifedipine was administered in therapeutic concentrations as a single i.v. bolus via the femoral vein. Prior to nifedipine treatment, adenosine (1.2 mumol/kg per min) produced a significant (P less than 0.05) 2-3 fold increase in LAD flow. This response was reduced markedly (P less than 0.05) in a dose-dependent manner by nifedipine (6-20 microgram/kg). Following administration of an average dose of 11 microgram/kg nifedipine, adenosine (1.2 mumol/kg per min) failed to elevate LAD flow significantly. Further, reactive hyperemia, produced by releasing a 30-s occlusion of the LAD, was significantly attenuated by these same nifedipine concentrations. The nifedipine-mediated attenuation could be partially overcome by prolonging the period of occlusion (60 s), or by increasing the rate of adenosine infusion. These results could not be accounted for by a nifedipine-mediated alteration of hemodynamics and suggest the possibility of pharmacological competition between adenosine and nifedipine at a vascular smooth muscle receptor.
Increased salivary flow stimulated by intravenous isoproterenol (IPR) (6 mg/kg) doubled the incidence of gastric stress ulceration in normal male mice, but not after submandibular sialadenectomy. The submandibular salivary glands in these mice secrete large amounts of several growth factors, including epidermal growth factor (EGF) and nerve growth factor (NGF). Intragastric instillation of a quantity of high molecular weight NGF equimolar to that in IPR-stimulated saliva doubled the incidence of stress ulcers after submandibular sialadenectomy. This action of NGF in vivo is not mediated by its nerve growth promoting properties nor its plasminogen activating property.
The interaction of homogeneous preparations of mouse submandibular gland nerve growth factor (NGF) with the classical complement pathway was studied. NGF was found to be capable of carrying out the enzyme activities of the first component (C1-) of the classical complement pathway (i.e., the cleavage of zymogen C4 and C2). NGF would not substitute for any other classical pathway component, C2-C9. The C1(-)-like activity of NGF was inhibited by human C1- inactivator. This interaction of NGF with the complement system may account for the previously described ability of NGF to accelerate the rate of contraction of experimentally induced wounds.
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The authors determined the platelet MAO activity of 57 psychotic patients after a placebo period and after 3-65 days of neuroleptic treatment. Platelet MAO activity significantly decreased in both men and women after neuroleptic treatment. The platelet MAO activity of neuroleptic-treated schizophrenic women was significantly less than that of drug-free schizophrenic women, who did not differ from normal women. There were trends in the same direction for the schizophrenic men. Previous studies that reported lower platelet MAO activity in neuroleptic-treated schizophrenic patients than in normal controls may have been influenced by this neuroleptic effect.