Current sex pre-selection methods.
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Biomedical subjects
Publications and source records attributed to R J Levin.
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Diet, dysfunction and disease induce primary and secondary changes in intestinal structure and function. The major techniques used to assess such changes in human and animal intestinal absorption and secretion in situ, in vivo and in vitro are reviewed concisely but critically and the problems of normalisation of the data explored. Exploitation of the various electrical potential differences generated by and across the intestinal epithelium allows the kinetic characterisation of the electrogenic glucose absorption mechanism, the measurement of functional lactase activity, the assessment of the thickness of the unstirred layer, the estimation of intestinal tonic (diffusive permeability and the recording of electrogenic secretion coupled with motility changes in the jejunum, in situ, of conscious man in health and disease. The use of animal intestine has allowed direct and indirect evidence of multiple hexose carriers to be obtained and a new technique allowing corrected kinetic parameters of Km and Jm to be estimated in vivo. Application of the technique to experimental conditions will allow a better assessment of the adaptive capabilities of the enterocytes absorptive functions.
Maximum absorptive capacities (Vmax) for the jejunum and ileum corrected for the presence of an unstirred layer of water have been calculated for glycine, valine and methionine in vivo in fowls per unit surface area and per region. Vmax per cm2 showed that ileal enterocytes had a greater absorbing capacity than jejunal for glycine and valine but not for methionine. Vmax for glycine and valine, calculated for the whole jejunum and ileum, however, were not different but for methionine the jejunal value was 1.9 times greater than the ileal.
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Oxygen consumption of human endometrial tissue was measured in vitro in air and high oxygen gas phases using an oxygen electrode. The oxygen consumption increased throughout the proliferative phase, peaking around ovulation and then decreasing during the secretory phase. This pattern persisted whether the oxygen consumption was expressed on a dry weight, DNA or protein basis. Storage of the tissue and mincing produced lower values of oxygen consumption.
1. Transfer potentials were obtained from everted jejunal sacs prepared from fed euthyroid, fasted euthyroid, fed hypothyroid and fasted hypothyroid rats by addition of serial concentrations of the dietary sugars glucose and galactose and the glucalogues 3-0-methyl glucose, alpha-methyl glucoside and 6-deoxy-D-glucose to the incubation fluids. The kinetic parameters of 'apparent Michaelis constant' (apparent Km) and maximum transfer potential difference (pdmax) obtained from the results were used to characterize the changes in the electrogenic transfer mechanisms for these substrates. 2. Analysis of the significant differential changes in values for 'apparent Km' and pdmax for the two dietary sugars and the three glucalogues indicated heterogeneity in the mechanisms for sugar transfer across the intestine and suggested a minimum of four possible carriers. 3. The validity of using glucalogues to characterize changes in the transfer mechanisms for the dietary sugars in different dietary and hormonal states was assessed. None of the kinetic parameters for electrogenic glucalogue transfer matched those for the dietary sugars in all the experimental conditions. The employment of glucalogues to assess changes in electrogenic transfer mechanisms for dietary sugars can thus lead to invalid conclusions. 4. Fasting decreased the 'apparent Km' of dietary sugars and the glucalogues. However, the pdmax values for glucose, galactose, and alpha-methyl glucoside decreased whereas those for 3-0-methyl glucose and 6-deoxy-D-glucose did not. 5. Hypothyroidism showed different effects in fed and fasted intestine. Because hypothyroidism induced a reduction in food intake, separation of the direct effects of the condition on electrogenic transfer from reduced food intake effect was not possible.
No experimental data on the regulatory mechanism of the change in vaginal blood flow occurring at sexual arousal exist. Six women were in a controlled laboratory study given atropine 0.035 mg/kg intravenously. The basal vaginal blood flow was recorded by a heat probe kept at set temperature on the vaginal wall. During sexual stimulation the flow was increased as in women when no drugs are applied and orgasm was unaffected as well. The neurotransmitter has been supposed to be acetylcholine but the present experiments suggest that it is not an atropine sensitive traditional muscarinic transmission. Methylatropine was given in five subjects and neither in these cases any effect on the vaginal vascular response was observed.
Vaginal fluid was collected on tampons self-inserted for 4 h daily during the menstrual cycles of coitally active, coitally inactive, ovulatory and non-ovulatory women. The daily hourly rate of fluid collected and its concentrations of Na+, K+, Cl- and Ca2+ were assessed. The fluid revealed a characteristic composition throughout all the menstrual cycles of 'high potassium-low sodium concentrations' compared to plasma, but no characteristic changes with the stage of the cycle. Occasional transient increases and decreases in Na+ and Cl- concentrations were observed, usually closely correlated with one another. Transient changes in K+ also occurred but these were not always correlated with other ions. In 9 cycles from 7 subjects the mean +/- s.e.m. levels (in mmol/kg fluid) of Na+ (82 +/- 4), K+ (30 +/- 2) and Cl- (79 +/- 4) in the first 7 days of the cycles were not significantly different from the Na+ (75 +/- 5), K+ (30 +/- 2) and Cl- (72 +/- 7) concentrations of the last 7 days of the cycles. This suggests that the differences in hormonal balance between the two phases of the menstrual cycle do not influence the ionic levels of vaginal fluid. The concentration of Ca2+ in 3 ovulating subjects varied between 1 and 5 mmol/kg fluid and often appeared to be inversely correlated with the amount of fluid collected.
Two new beta-adrenergic blocking agents, timolol and MK-761, were found to effectively antagonize the positive inotropic effects of isoproterenol on isolated cat papillary muscles without depressing contractile force. However, appropriate doses of these beta-adrenergic blockers (ie, 12.5--25 microgram/kg) did not significantly prolong survival in hemorrhagic shock in anesthetized cats. MK-761 prevented some of the plasma accumulations of myocardial depressant factor (MDF) during shock. Nevertheless both beta-blockers failed to prevent the accumulation of the lysosomal protease cathepsin D or peptide fragments (ie, amino-nitrogen groups) in the blood during shock. We conclude that neither agent is of significant benefit in severe hemorrhagic shock, and probably beta-adrenergic blockade is not a productive approach to pursue in the therapeutics of hemorrhagic shock.
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The jejunal mechanisms for the electrogenic transfer of four neutral amino acids (alanine, leucine, methionine, valine) and for sarcosine were characterised by an electrical method in vitro. The values for apparent Km obtained electrically agree well with those assessed by conventional chemical techniques. Hypothyroidism and/or fasting rats for 3 days induced differential changes in the apparent Km and p.d.max for the various amino acids. These alterations were interpreted as indicating the presence of at least three mechanisms for neutral amino acid transfer and one for sarcosine. In euthyroid rats, only alanine showed changes in apparent Km (decrease) and p.d.max (decrease) after fasting for 3 days. With hypothyroidism the kinetic parameters of electrogenic transfer for alanine, valine and sarcosine were significantly altered while those for leucine and methionine were unaffected.
Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 +/- 24 mum: mean +/- SEM) was significantly thicker than in 10 patients with active coeliac disease (442 +/- 23 mum) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 +/- 49 mum). There were similar differences in the values of ;Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 +/- 6 mM) active coeliac patients (11 +/- 1 mM) and treated coeliac patients (31 +/- 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6.8 +/- 0.7 mV) was lower than in controls (7.6 +/- 0.6 mV) but not significantly so, while the PDmax in the treated coeliac group (10.6 +/- 0.9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (;Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.
Recordings of transmural potential difference (PD) across the jejunum of conscious man in situ are characterised by spontaneous fluctuations of up to 10 mV. In 25 of 31 subjects (comprising seven normal controls and 24 patients under investigation for malabsorption, six of whom had coeliac disease) we observed a clear association between these fluctuations and changes in intraluminal pressure recorded at the same site. The most frequent PD changes were associated with type III pressure waves. These consisted predominantly of large waver (3-1 +/- 0-1 mV; mean +/- SEM, n = 317) which reached maximal amplitude approximately 45 seconds after the pressure peak and had a duration of 120 +/- 3 s, but also included less frequent spikes (0-5 +/- 0-1 mV; n = 110) concurrent with the pressure wave with a duration of 5 +/- 1 s. Although by recording at two sites in the jejunum 10 cm apart we were able to demonstrate that type III pressure waves appeared to be propagated aborally at a median rate of 60 cm per minute, the apparent rates of propagation of the corresponding PD waves were much more variable. The largest PD changes (7-8 +/- 0-4 mV; n = 19), lasting several minutes, were found in association with runs of type I waves (basic rhythm) superimposed on a type III wave. Both pressure and PD activities were suppressed by intramuscular propantheline bromide. Intraluminal pilocarpine caused a transient rise in PD not always accompanied by a change in pressure. Distention of the jejunum by rapid injection of a bolus of isotonic sodium chloride produced a delayed rise in the PD which could be prevented by prior administration of propantheline bromide. Experiments using Thirty-Vella loops of proximal jejunum in conscious dogs confirmed the effect of jejunal distension on the PD and also demonstrated that spontaneous retching is preceded by an increase in the PD. Consideration of these results in conjunction with data from other workers suggests the hypothesis that the larger spontaneous fluctuations in transmural PD in the jejunum of conscious man are caused by changes in electrogenic secretion associated with intestinal motility and mediated by cholinergic mechanisms. The possible association of increased secretory activity with motility may have functions of lubrication as well as diluting and mixing the chyme for easier digestion and absorption.