The uterine endometrium and isthmic oviduct of the ewe: does progesterone act as an antiestrogen?
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Biomedical subjects
Publications and source records attributed to J Wild.
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The construction of a plasmid carrying the ilvC::lacZ fusion is described. This plasmid provides a convenient source of template deoxyribonucleic acid for use in an in vitro protein-synthesizing system. We screened strains deleted in regions of the ilv cluster for their ability to support ilvC-dependent beta-galactosidase synthesis. The fact that two deletions prevented beta-galactosidase production indicated that ilv-C expression is under positive control. By use of plasmids carrying the positive-control factor structural gene ilvY, we were able to restore protein-synthesizing ability to these strains. These plasmids also enabled us to map ilvY between ilvA and ilvC.
Some of the characteristics of men, with known risk factors, who were most likely to respond to an invitation to be screened in a national randomized clinical trial to prevent heart disease were determined in 18,872 men, 35-57 years of age, members of the Kaiser Foundation Health Plan of Oregon. Demographic characteristics and risk factor variables (blood pressure, blood cholesterol, and cigarette smoking levels) were abstracted from medical records. The men were ranked high priority or low priority according to level of risk. All age-eligible men in the health plan received at least one invitation to be screened, with high-priority men receiving more invitations. Despite concentrated efforts to bring them in, less than one-half the high-priority men were screened. Participants were older and wealthier than non-participants, and more likely to have more dependents and to routinely use medical services. Whether or not a man received a medical care service within the preceding two years was a powerful discriminating variable in both the univariate and multivariate analyses reported. The findings suggest that health care programs serving a stable population group should give more consideration to screening in routine medical care.
Utilization of D-amino acids being substrates of D-amino acid dehydrogenase of Salmonella typhimurium was examined. The experiments were done with wild type strains and the mutants dadA missing the enzyme activity and dadR in which its synthesis is released from catabolite repression. Growth on D-tryptophan, D-histidine and D-methionine used as precursors of the L-amino acids was faster when the respective auxotrophs carried dadR mutations. The dadR mutants grew faster when D-or L-alanine was present as a sole source of nitrogen. Experiments with D-amino acid dehydrogenase in vitro provided evidence that D-tryptophan is its substrate with a very low affinity to the dehydrogenase.
An in vitro protein-synthesizing system has been developed to study the mechanism of induction of ilvC gene in Escherichia coli strain K-12. Deoxyribonucleic acid (DNA) from a lambda phage carrying an ilvC-lac fusion was employed as a template for the in vitro synthesis of beta-galactosidase under the control of the ilvC promoter. The use of this template allowed an investigation of the components required for induction of the ilvC gene and the kinetics of the induction. The in vitro synthesis of beta-galactosidase under the control of the ilvC promoter was found to be DNA, acetohydroxy acid, and guanosine-3'-diphosphate-5'-diphosphate dependent, and sensitive to rifampin, actinomycin D, and chloramphenicol. Uncoupling experiments indicate that the inducer, acetohydroxybutyrate, acts at the transcriptional level. Investigation of a proposed noninducible ilvC regulatory mutant has shown normal induction in vitro. It was also observed that an intact ilvA gene is not required for the induction of the ilvC gene.
It has been found that synthesis of D-amino acid dehydrogenase in Salmonella typhimurium is stimulated by cyclic AMP and crp gene product. This indicates that catabolic control of the dehydrogenase resembles other bacterial systems of catabolic repression. We have isolated S. typhimurium mutants, dadR, which are resistant to L-methionine-interference with D-histidine utilization and are able to utilize D-tryptophan as a precursor of L-tryptophan. Mapping data indicate that the dadR locus is closely linked to dadA coding for the structure of D-amino acid dehydrogenase. The synthesis of the dehydrogenase in dadR mutants is completely insensitive to the repression by glucose, but remains inducible by L-alanine. We conclude thereof that dadR mutants have changes in the promoter region which increase the expression of the dadA gene in the presence of glucose metabolism. A likely possibility that induction of the dad operon by alanine might be under positive control is discussed.
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It has been shown that women receiving oral contraceptives have increased levels of serum vitamin A. High vitamin A levels may constitute a teratogenic hazard and it has been suggested that women who conceive soon after discontinuing oral contraceptive therapy may be especially at risk to this hazard.We have confirmed a significant increase in vitamin A levels in women taking oral contraceptives. During early pregnancy there is no significant difference in vitamin A levels between women who have recently been taking oral contraceptives and those who have not. We have been unable to show that either taking oral contraceptives shortly before pregnancy or a high vitamin A level during the first trimester of pregnancy, comparable to that of a woman taking oral contraceptives, has any detrimental effect on the outcome of pregnancy. It seems unlikely that women who conceive soon after discontinuing oral contraception run any teratogenic risk from increased vitamin A levels.
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A sensitive HPLC-fluorescence method for determining total endogenous plasma homocysteine (Hcy), cysteine (Cys) and cysteinylglycine (Cys-Gly) following derivatization with ammonium 7-fluoro 2,1,3-benzoxadiazole-4-sulphonate (SBD-F) is described. Quantitation utilizes an internal standard, 2-mercaptoethylamine. The derivatization procedure has been optimized for concentration of SBD-F, reducing agent (tributylphosphine) and temperature. Findings indicate that values for plasma determinations vary according to the nature of the matrix in which calibration standards are made up. If quantitation is based on a peak height ratio, then standards should be made up in either pH 7.4 phosphate buffered saline or plasma taking into account the endogenous thiol concentration. These findings are based on calibration data, and 30 plasma samples quantified using thiol standards made up in plasma, pH 7.4 and pH 9.5 buffers. By defining how this matrix/pH effect influences thiol quantitation, it should be possible to make a more meaningful comparison of Hcy measurements between laboratories. The chromatographic separation was investigated at several mobile-phase pH values with the following conditions ascertained to be optimal: a mobile phase consisting of 5% (v/v) acetonitrile in 0.1 M KH2PO4, pH 2.15 was run at a flow rate of 0.5 mL/min. It was used in conjunction with a Supelco LC-18 base deactivated analytical column (150 x 4.6 cm i.d. 3 microM bonded silica). The internal standard and thiols were measured by fluorescence detection at 385 nm excitation and 515 nm emmission. Plasma levels are easily measured in a 100 microL volume. Storage for 2 months at -20 degrees C resulted in no deterioration of thiols. Furthermore, no difference in thiol levels was observed between bloods collected in lithium heparin and EDTA. Collected blood should, however, be separated as soon as possible to avoid red cell metabolism of Hcy which was observed in a case of hyperhomocysteinemia. Once derivatized, thiols are stable for at least one week at +4 degrees C.
The Women Helping to Empower and Enhance Lives (WHEEL) Project focused on female sexual partners of injection drug users (i.d.u.s). It was conducted in five sites, three within and two outside the continental United States. The study's two main intervention goals were to (a) reduce HIV-related sexual risk behaviors and (b) reduce HIV-related drug risk behaviors. The Project also featured needs assessment, planning, and staff training components. Baseline data were collected on 2,794 women, which made this the largest study of noninjecting female sexual partners of i.d.u.s in the United States. Six-month follow-up data were obtained on 1,953 women. The Wheel Project tested two interventions: an individual intervention and a group intervention. The study found significant reductions in drug use and risky sexual behaviors for the 6-month follow-up sample for both interventions. These changes were substantial and point to the viability of both interventions for this population of sexual partners of injection drug users.
Vigabatrin is an antiepileptic drug for the treatment of partial seizures. The anticonvulsant effect is achieved by irreversible inhibition of the enzyme GABA-transaminase which catalyses the inactivation of GABA. Vigabatrin has been associated with visual field loss and electrophysiological abnormalities. The purpose of the study was to determine any alterations in normal volunteers of the visual field and the visual electrophysiology resulting from a short exposure to vigabatrin. A three-way, double-blind study of placebo, carbamazepine and vigabatrin was undertaken at baseline and on days two, four and nine. Seven subjects completed all three cycles and 14 subjects (six females and eight males; mean age 27.3 years SD 6.7) completed at least one cycle. Static threshold automated perimetry comprised Humphrey Visual Field Analyzer Programs 30-2 and 30/60-2. Electro-oculography and electroretinograms were performed with undilated pupils using the Medelec Ganzfeld stimulator GS2000. The visual field was unaffected by placebo, carbamazepine or vigabatrin. The group mean amplitudes and latencies for the scotopic ERG, 30 Hz flicker ERG and the oscillatory potentials remained unchanged for any cycle. The group mean photopic ERG b-wave latency increased from baseline (p<0.05); no significant change occurred with carbamazepine or placebo. The group mean Arden Index for vigabatrin decreased from baseline to day 9 (p<0.01); no significant differences were present for carbamazepine or placebo. Vigabatrin has a rapid effect on both the photopic ERG and the EOG; however, the changes merely reflect alterations in retinal GABA levels secondary to concomitant blocking of GABA transaminase by existing vigabatrin therapy.
OBJECTIVE: This study examined the 7-year outcome of speech/language (S/L) impaired and control children selected from a community sample at age 5 years. METHOD: Two hundred fifteen children completed a variety of speech and language tests at age 12 years. Children with S/L impairment were further classified as "speech only," "language only," or "speech and language impaired." RESULTS: More than 72% of children who had S/L impairment at age 5 remained impaired at age 12. Children with both speech and language problems were most likely to remain S/L impaired; 81% had some kind of S/L impairment at follow-up. Similarly, children with both expressive and receptive language impairment were more likely to show expressive or receptive impairment at follow-up than children with expressive impairment alone. One third of time 1 controls had S/L problems at follow-up, and of these 82% had speech impairment only. CONCLUSIONS: S/L impairment identified at age 5 has long-lasting effects. More pervasive problems were associated with poorer outcomes. Screening at age 5 may be useful, as most serious S/L problems that emerged by middle childhood could be identified at age 5. The effects of S/L treatment require further study.
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The diagnosis of cardiac allograft rejection is currently based on endomyocardial biopsy and histologic evaluation. Since the introduction of cyclosporine, cardiac biopsy has been recognized as the only reliable method of diagnosis. From July 1985 to June 1986, 22 transplant patients were studied during the early posttransplant period to evaluate other characteristics of allograft rejection. The immunosuppressive protocol included cyclosporine, azathioprine, prednisone, and prophylactic rabbit antithymocyte globulin. Acute rejection was established by standard histologic criteria. Twenty-four positive and 123 negative biopsy findings were obtained. Clinical variables (age, sex, immunosuppressive regimen, cyclosporine dosage, ECG voltage), biologic variables (level of cyclosporine, white blood cells, blood urea nitrogen, creatinine, bilirubin, prolactin, urinary polyamines, blood type, HLA typing), and immunologic variables (T-cell subsets) were analyzed in regard to the histologic diagnosis of acute rejection. Four variables (WBC, prolactin, total urinary polyamines, N-acetyl putrescine) were found to have a significant univariate association with acute rejection. These variables were studied by multivariate discriminant analysis. The only factors found to have independent predictive value for acute rejection were prolactin and N-acetyl putrescine peaks occurring before acute rejection. When we used these factors, a discriminant function correctly predicted acute rejection episodes, as well as negative biopsy results, in 74% of the cases in this group of patients.