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Biomedical subjects

B Birch

Publications and source records attributed to B Birch.

At least 19 recordsLinked to original sources

Seminal tissue factor revisited.

Studies of seminal tissue factor (TF) are few and mostly based on small numbers. Due to the reported lack of factor (F) X in semen, it has been suggested that TF may not have a role in seminal coagulum formation. However, recent identification of a number of haemostatic factors in semen justifies a re-evaluation of its occurrence. Semen specimens were collected from sub-fertile (n = 19), normally fertile (n = 33), semen donors (n = 30) and vasectomized subjects (n = 62), some fractionated into sperm, a prostasome-rich fraction and seminal plasma. Functional and antigenic TF levels were measured and related to conventional fertility parameters. Semen contains high concentration of functional and antigenic TF. Most TF was found in seminal plasma prepared by low-speed centrifugation. When further fractionated by ultracentrifugation much of this may reside in the pellet (prostasomal fraction). It was also detectable on sperm. TF antigen levels were higher in vasectomized subjects than sub-fertile, normally fertile, donor (p = 0.02) and a 'pooled normal semen parameters' (PNSP) stratification (derived from a combination of measurements) (p = 0.06). The sub-fertile group showed a wider variation than normal, donor or the PNSP subjects. Seminal TF antigen levels correlated significantly with sperm agglutination (p = 0.03) and abnormal sperm morphology (p = 0.04). Subjects with anti-sperm antibodies also showed high TF antigen levels. In conclusion, semen contains functional and antigenic TF at high concentrations. A full complement of clotting factors probably exists in semen, so some pro-coagulant role for TF should not be excluded. Decreased seminal TF levels appear to be associated with seminal parameters that are known to favour male fertility.

Adult↗

Progesterone: a novel adjunct to intravesical chemotherapy.

OBJECTIVE: To investigate the effect of progesterone on multidrug-resistant urothelial cell lines, as the failure of intravesical chemotherapeutic drugs is often caused by multidrug resistance (MDR), mediated by the drug efflux pump P-glycoprotein (PGP), the function of which can be down-regulated by various compounds including steroid hormones. MATERIALS AND METHODS: Two urothelial cell lines (RT112S and MGH-U1S) and their MDR sublines (RT112R, to cisplatin; and MGH-U1R, a cell line expressing PGP) were used to assess the cytotoxic effects of progesterone, epirubicin and their combination. Cytotoxicity was assessed using a tetrazolium-based assay and in situ confocal microscopy. RESULTS: Cell lines sensitive to epirubicin (MGH-U1S, RT112S and RT112R) required a much lower dose of epirubicin to kill half the cells than did the MDR cell line. Progesterone was intrinsically cytotoxic to all cell lines with little difference among them. Combined therapy had no cumulative effect on epirubicin-sensitive cell lines, but reversed MDR in the MGHU1R cell line, both assessed by confocal microscopy and by the tetrazolium assay. CONCLUSIONS: Progesterone can reverse MDR in urothelial cells in vitro. This, combined with its effects on cell differentiation and apoptosis, together with its safety and tolerability compared to other MDR agents, suggests it may be a valuable adjunct to intravesical chemotherapy.

Administration, Intravesical↗

Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines: a study with midazolam and the benzodiazepine antagonist, flumazenil.

Sixteen healthy volunteers were administered midazolam followed by placebo or the benzodiazepine antagonist, flumazenil, in a double-blind, cross-over study. Flumazenil reversed midazolam-induced sedation on the subjective, psychophysiological and motor indices used. In contrast, there was little evidence of any reversal of amnesic effects, which were assessed using both direct (explicit) and indirect (implicit) measures of memory. Results are discussed in terms of dissociating the sedative and amnesic effects of benzodiazepines.

Adult↗

Transfer RNA and ribosomal RNA are synthesized from the same pyrimidine nucleotide pool.

We have tested the hypothesis [Wiegers, Kramer, Klapproth & Hilz (1976) Eur. J. Biochem. 64. 535-540] that the synthesis of rRNA in the nucleolus may have a partially independent supply of nucleoside triphosphates that is not completely suppressed when cells are supplied with exogenous nucleosides. For the slime mould, Physarum polycephalum, and Chinese hamster ovary cells in culture, the specific activities (3H/32P) of UMP and CMP in tRNA, which is synthesised in the nucleoplasm, and rRNA were compared after continuous labelling with [3H]uridine and [32P]phosphate. No differences were found, suggesting that transcription throughout the nucleus draws on a common supply of pyrimidine triphosphates that is uniformly labelled from exogenous [3H]uridine. As a control of the radioactive labelling schedule, a similar experiment was carried out with the prokaryote, Escherichia coli, and identical results were obtained.

Animals↗

Regulation of protein synthesis in the plasmodial phase of Physarum polycephalum.

1. The rate of protein synthesis changes very little during the first 2-3 h (S phase) of the nuclear division cycle in plasmodia of Physarum polycephalum and then increases continuously during G2 phase, so that by the end of the cycle the rate has doubled relative to that in S phase. Protein synthesis appears to continue during mitosis. 2. Fractionation of extracts of plasmodia, labeled with [3H]lysine for 1 h, by two-dimensional electrophoresis indicated that most if not all proteins are synthesised throughout the nuclear division cycle. However, two metabolically stable polypeptides, the synthesis of which occurs predominantly in Gs phase, were detected. 3. Using a double-labelling procedure, the differential rates of synthesis of 30 relatively abundant polypeptides were measured in relation to the nuclear division cycle. As a group, their differential rates of synthesis increase during the cycle so that their actual rates of synthesis increase 4-6-fold. This implies that their synthesis is regulated over and above any simple change due to a doubling in the number of genes during S phase.

Cell Cycle↗

The uptake and metabolism of uridine by the slime mould Physarum polycephalum.

1. Uridine is taken up by microplasmodia of Physarum polycephalum via a saturatable transport system with an apparent Km of 29 muM. An intracellular concentration significantly higher than that in the growth medium is attained, suggesting that the uptake is an active process. Both deoxyribonucleosides and ribonucleosides are competitive inhibitors of the uptake of uridine. 2. In contrast, the rate of entry of uridine into surface plasmodia is a linear function of the concentration of the nucleoside in the growth medium, and the uptake is not inhibited by other nucleosides. 3. As well as serving as a source of pyrimidine nucleotides for the synthesis of nucleic acids, uridine is also catabolised by P. polycephalum. Uracil accumulates in the growth medium and there is also significant conversion of C-2 of the pyrimidine ring to CO2. The proportion of uridine subject to catabolism in surface plasmodia is less than that observed for microplasmodia.

Binding, Competitive↗