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Biomedical subjects

R Little

Publications and source records attributed to R Little.

66 records · Page 4Linked to original sources

Reproductive function during fasting in men.

To investigate reproductive function during fasting, six men 20-74% over ideal body weight completed an 18-day study consisting of a 3-day control period, a 10-day total fast, and a 5-day refeeding period. All men lost at least 4.1% of total weight and demonstrated ketonemia and ketonuria. The FSH response to LRH (0.2 microgram/min for 4 h) stimulation was significantly lower (P less than 0.05) during fasting and remained so during refeeding. Serum FSH concentrations were significantly lower (P less than 0.05) during the fast in five of six patients compared to those during the control period, whereas serum LH concentrations were unchanged. The effects of fasting on endogenous LH and FSH pulsations were studied by obtaining serum at 20-min intervals for 6 h on days 2, 11, and 16. Neither the amplitude nor the frequency of LH and FSH pulsations changed significantly during fasting or refeeding. Serum testosterone concentrations were significantly lower (P less than 0.025) by fasting day 9 compared to control values. The 24-h urinary excretion of both LH and FSH increased significantly (P less than 0.05) by fasting day 6 and reached a maximum by fasting day 8. Urinary LH excretion did not return to normal after 3 days of refeeding, whereas urinary FSH excretion returned to baseline by the first day of refeeding. We conclude that during short term fasting in obese men: 1) serum FSH concentrations decrease, 2) the pituitary responsiveness of FSH and LRH is blunted, 3) serum testosterone decreases, and 4) the urinary excretion of both LH and FSH increase.

Adult↗

Regulation of RNA polymerase synthesis. Conditional lethal amber mutations in the beta subunit gene.

Amber mutations in the rpoB gene specifying the beta subunit of RNA polymerase coupled with conditional amber suppressors were used to restrict the synthesis of core RNA polymerase in strains of Escherichia coli. Such a restriction stimulated transcription of genetic units containing RNA polymerase subunit genes. Within the L10 transcription unit (genetic structure: promotor (PL10), rplJ (L10), rplL (L7/L12), attenuator, rpoB (beta), rpoC (beta'), terminator), the initiation of transcription at the promotor was enhanced and termination at the transcription attenuator was relaxed. Transcription of the genetic unit containing the rpoA gene (alpha) was also enhanced. In the strain containing a non-polar amber mutation, the synthesis rate of the beta' subunit protein during the restriction correlated with the level of transcription of the beta and beta' genes. In contrast, synthesis of L7/L12 ribosomal protein remained essentially unaltered in spite of the elevated levels of L10-L7/L12 mRNA.

DNA-Directed RNA Polymerases↗

Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro.

The effects of LHRH and a potent LHRH agonist (LHRHa) on invitro testosterone production by enzyme-dispersed rat interstitial cells were evaluated. In a series of in vitro experiments, neither basal nor human menopausal gonadotropin (hMG)-stimulated testosterone production were significantly affected by doses of LHRH or LHRHa ranging from 10(-12)--10(-5) M. In addition, adult male rats were treated chronically with once daily injections of LHRH or LHRHa (2 micrograms/rat) or the vehicle for 1--7 days and decapitated 24 h after the last injection, and their testes were removed and weighed. Testicular weights decreased significantly by day 3 and were maximally decreased by day 6. In vitro testosterone production in response to 1--5 mIU human menopausal gonadotropin was markedly impaired (greater than 50%) in cells from rats treated with LHRHa for 2 days or longer and in rats treated with LHRH longer than 3 days. These data indicate that 1) LHRH and LHRHa do not alter in vitro testosterone production by dispersed rat interstitial cells and 2) interstitial cells of rats pretreated with LHRH and LHRHa exhibited impaired in vitro testosterone production. The data do not, however, rule out a direct effect of LHRH or LHRHa on testicular systems other than those involved in steroidogenesis.

Animals↗

Expression of RNA polymerase and ribosome component genes in Escherichia coli mutants having conditionally defective RNA polymerases.

The expression of the genes coding for the beta and beta' subunits of RNA polymerase, ribosomal RNA, ribosomal proteins, and beta-galactosidase was investigated in strains carrying conditionally lethal mutations affecting either RNA polymerase core assembly or RNA polymerase enzyme activity. The mutant strain XH56 produces a temperature-sensitive beta' subunit and at 42 degrees C is defective in RNA chain initiation; consequently, little or no transcription occurs at the restrictive temperature. A partial restriction, produced by shifting the strain to 39 degrees C, resulted in a rapid fivefold increase in the transcription of the rpoB and C genes and in the synthesis of the beta- and beta'-subunit proteins for which they code. The RNA polymerase assembly-defective strains A2R7 and TS4 exhibited a 1.5- to 2-fold increase in the transcription of the rpoB and C genes and in the synthesis of beta- and beta-subunit proteins after prolonged restriction. These results demonstrate (i) that regulation of the synthesis of the beta- and beta-RNA polymerase subunits is under these conditions primarily transcriptional rather than translational, and (ii) that a stimulation of rpoB and C gene expression results from a restriction on RNA synthesis caused by either RNA polymerase inactivation or inhibition of its assembly. During restriction of the mutant strains, the transcription of the ribosome component genes exhibited patterns which were similar to transcription of the rpoB and C genes, supporting the evidence that genes coding for RNA polymerase are cotranscribed with ribosomal protein genes; transcription of the lacZ gene was observed to decrease concomitant with the stimulation of the rpoB and C genes.

Bacterial Proteins↗

Studies on the central integration of excitatory chemoreceptor influences and inhibitory baroreceptor and cardiac receptor influences.

Experiments were performed on cats to explore the integrated cardiovascular responses when excitatory (chemoreceptor) and inhibitory (baroreceptor or cardiac receptor) influences are simultaneously presented to the medullary cardiovascular areas. At a given sinus pressure in the low or medium pressure range, the systemic blood pressure and the vascular resistance were higher when the chemoreceptors were stimulated, while a high, pulsating sinus pressure, i.e.a strong baroreceptor stimulation, could suppress completely even an intense chemoreceptor activation. Thus, the set point and the gain of the baroreflex were increased by a concomitant chemoreceptor activation. These effects are compatible with a simple, mutual 'summation' of excitatory and inhibitory influences on a common population of central vasomotor neurons. The reflex vasodilator effects elicited via vagal cardiac afferents were found to be more effectively suppressed by a concomitant chemoreceptor stimulation than were the baroreceptor effects, provided a primary chemoreceptor response (bradycardia) was at hand, while the heart rate responses were essentially uninfluenced by the prevailing chemoreceptor activity. This chemoreceptor suppression of the reflex vasodilatation from cardiac receptors, which may be of great importance in hypoxic situations, e.g. during a dive, suggests a more complex, neuronal interaction between the two reflex mechanisms in the CNS.

Afferent Pathways↗

Circulatory responses to stimulation of the carotid body chemoreceptors in the cat.

Cardiovascular responses to carotid body chemoreceptor stimulation were followed in the 'curairzed', vagotomized, artificially ventilated cat. Stimulation of the chemoreceptors by perfusion of the carotid sinus regions with venous blood induced a reflex vasconstriction in skeletal muscle, kidney, intestine and skin, and, in most cases, an increased heart rate. A comparison of the chemoreceptor reflex responses with those obtained by direct electrical stimulation of the regional vasomotor fibres indicated that in chemorecptor reflexes the vasomotor fibre activity increased to the same extent in skeletal muscle and intestinal resistance vessels and, probably, in the nutritional skin vessels but to a smaller extent in the renal vessels and the skeletal muscle capacitance vessels. The renal vessels and the muscle capacitance vessels seemed, however, to respond more during chemoreceptor stimulation than when the barorecptors were unloaded, indicating that anexcitation of the bulbar vasomotor centre is more effective than the withdroawal of an inhibitory restraint in activating the vasomotor fibres to these vascular sections.

Animals↗

Aspects of the central integration of arterial baroreceptor and cardiac ventricular receptor reflexes in the cat.

The possible central integrative mechanisms, responsible for the earlier reported, differentiated reflex engagement of the renal and muscle vessels and the heart from cardiac ventricular receptors and arterial baroreceptors, respectively, were analyzed in atropinized cats. The reflux renal vessel, muscle vessel and heart rate responses, expressed as per cent of maximum, to graded activations of arterial baroreceptors (sinus pressure variations) and stimulations of ventricular receptor afferents in the cardiac nerve were systematically compared. Cardiac nerve stimulation with low frequencies was found to elicit more pronounced reflex renal vessel responses than muscle vessel and heart rate responses. In contrast, elevations of sinus pressure induced equally pronounced renal and muscle vessel responses. High frequency cardiac nerve stimulation elicited maximal reflex renal vessel responses, but only submaximal effects on muscle vessels and heart rate, while intense baroreceptor stimulation induced maximal reflex effector responses throughout. The submaximal heart rate response to cardiac nerve stimulation is probably due to a simultaneous activation of excitatory afferents. On the other hand, the less pronounced muscle than renal vessel responses when the cardiac nerve was stimulated probably reflect a relatively sparse innervation of muscle vasomotor neurons by ventricular receptor afferents, which seem instead to be preferentially oriented towards renal vasomotor and, possibly, cardiac motor neurons.

Animals↗

The influence of rheological and collapse factors on pre- and post-capillary flow resistances in the skeletal muscle vascular bed of the cat.

The importance of passive-elastic changes of vascular dimensions and shifts in regional effective viscosity for the pre-/postcapillary resistance ratio (RA/RV), and hence mean capillary pressure (PC), was analyzed in cat calf muscles. Reductions of mean venous distending pressure below 6-8 mm Hg induced marked RV increases due to escalating venous collapse. This mechanism tends to delimit the PC reductions and rate of transcapillary fluid absorption during intense precapillary vasoconstriction. Comparisons of RA/RV for erythrocyte suspensions (Hct 40-50) and cellfree perfusates at identical vascular dimensions showed that RA/RV was considerably higher, and PC correspondingly lower, for the erythrocyte suspension except at very low flows. This RA/RV difference increased with increasing flow and at very high flows PC was about 10 mm Hg lower during perfusion with the erythrocyte suspension. These findings apparently diverge from the known influence of the tube radius and linear flow velocity on effective in vitro viscosity of blood. Since distal precapillary and proximal capillary sections, both having smaller diameters than the erythrocytes, are located upstream to the point of filtration-absorption equilibrium, they contribute in this respect to RA. It is therefore suggested that the increasing RA/RV with erythrocyte perfusion, particularly at higher flows, is not due to genuine viscosity factors but to friction losses when cells in "bolus flow" are squeezed through the narrowest precapillary sections.

Animals↗

Application of a high performance liquid chromatography method for screening of aldehyde dehydrogenase isozyme deficiency in hair roots from different ethnic groups.

A sensitive high performance liquid chromatography method has been used to measure aldehyde dehydrogenase (ALDH) activity in hair roots from Caucasian and Japanese subjects. Kinetic studies confirmed previous isoelectric focusing results that hair roots from Caucasians have two forms of ALDH, one low Km form and another high Km form, while hair roots from Japanese individuals who show a flushing reaction after ethanol intake lack, or have low activity of, the low Km form. By taking the ratio of the activities measured at a low (3 microM) and a high (75 microM) concentration of the substrate (3,4-dihydroxyphenylacetaldehyde), a suitable index for ALDH deficiency was obtained. The ratio varied between 1.6 and 3.5 for Caucasians and between 7 and 23 for Japanese flushers, and it was 2.5 for a Japanese nonflusher. The current method allows a more quantitative and qualitative assessment of the ALDH isozyme pattern in hair roots than that obtained with the isoelectric focusing technique.

3,4-Dihydroxyphenylacetic Acid↗

TNF alpha and IL-6 involvement in surgical trauma. II. In vitro cytokine production.

The study aimed to correlate TNF alpha and IL-6 dynamics during surgical trauma as well as the changes which appear in the circulating monocytes' response after LPS stimulation in vitro. Three patients with major abdominal operations were chosen and serial blood samples were taken before, during and after the operation. Normal unmatched individuals were used as control group during a two hours bed resting period. Both TNF alpha and IL-6 in vitro production showed similar patterns with an initial drop and almost full recovery 24 hours after the operation. We propose a model for TNF alpha and IL-6 role in trauma induced inflammation.

Abdominal Cavity↗