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Biomedical subjects

J H Johnson

Publications and source records attributed to J H Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Serotonergic mediation of a negative feedback effect of estrogen on luteinizing hormone release in ovariectomized rats.

Effects of the serotonin receptor antagonists ketanserin, metergoline, and methysergide on LH release were tested in ovariectomized (OVX) rats pretreated with estradiol benzoate (EB) (5 micrograms/100 g BW) on each of the 2 days preceding the experiment. LH concentration measured by RIA in plasma samples obtained at 10 min intervals was analyzed using the PULSAR computer program to identify and characterize pulses observed in the LH profile of each rat individually. Multiple pulses were identified in seven of seven OVX rats but in only two of eight OVX rats primed with EB. Multiple pulses were identified in OVX EB-primed rats pretreated with ketanserin (six of seven), metergoline (three of seven), and methysergide (six of eight). Administration of the serotonin (5HT) agonist quipazine (2 mg/kg iv) to OVX rats inhibited pulsatile LH release and depressed mean plasma concentrations for approximately 45 min. This inhibitory response was antagonized by pretreatment of the OVX animals with ketanserin. These results suggest that 1) quipazine inhibits pulsatile LH release in OVX rats by a serotonin2 receptor mechanism; and 2) the inhibitory effect of estrogen on pulsatile LH release may also be mediated, at least in part, via 5HT2 systems.

Animals↗
PubMed1988

Aerocyanidin, a new antibiotic produced by Chromobacterium violaceum.

Aerocyanidin, a new antibiotic containing an isonitrile group, has been isolated from fermentations of Chromobacterium violaceum ATCC 53434. Structure 1 was assigned on the bais of spectroscopic characterization of the antibiotic and of a degradation product that results from treatment with base. The antibiotic is primarily active against Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1987

Opiate-serotonin synergism stimulating luteinizing hormone release in estrogen-progesterone-primed ovariectomized rats: mediation by serotonin2 receptors.

A tonic inhibition of LH release by endogenous opiate systems is apparent after administration of opiate antagonists to ovariectomized estrogen-progesterone-primed rats. In the presence of a serotonin agonist, morphine has been found to stimulate LH release in ovariectomized animals. Thus, in the present study the individual effects as well as interactions of the opiate and serotonin (5HT) systems have been examined using morphine and quipazine, respectively, as agonists and ketanserin (5HT2) and methysergide (5HT1 and 5HT2) as antagonists. Rats ovariectomized 2-4 weeks beforehand were primed with estradiol benzoate (15 micrograms; day 0) and progesterone (5 mg; day 2). Serial blood samples were collected from unrestrained rats via a jugular cannula inserted 3 days before, and plasma LH was measured by RIA. Neither morphine (4 mg sulfate) nor quipazine (2 mg/kg) administered iv at 1200 h significantly elevated plasma LH at 1210, 1220, or 1230 h compared to levels at 1200 h, although plasma LH concentrations at these times were significantly greater than those in animals receiving saline at 1200 h. However, injection of both morphine and quipazine at 1200 h greatly augmented LH release at 1210, 1220, and 1230 h compared to the response to either drug alone. The duration of the significant elevation of plasma LH was limited to 10 min by ketanserin (2.5 mg/kg, ip, at 0900 h) and to 20 min by methysergide (10 mg/kg, ip, at 0900 h), suggesting mediation of this response by 5HT2 receptors. These results suggest the possibility of an important interaction between opiate and serotonergic systems in controlling the release of LH and raise the intriguing question of its role, if any, in controlling events of the estrous cycle.

Animals↗
PubMed1987

An investigation into the effect of a ceramic particle trap on the chemical mutagens in diesel exhaust.

Diesel exhaust particles and vapor phase samples were collected from the diluted (15:1) exhaust of a 10.4 L displacement medium-duty engine (Caterpillar 3208), operated under EPA steady-state cycle Modes 4 and 5 conditions for load (50 and 75 percent, respectively) and speed (1680 rpm). Baseline (uncontrolled) emissions were compared to the exhaust modified by the use of an uncatalyzed monolithic ceramic trap (Corning). The Salmonella/microsome mutagenicity bioassay (Ames Test) was used to direct the course of chemical analyses. Total particulate matter (TPM), soluble organic fraction (SOF) (from TPM), sulfate fraction (SO4) (from TPM), and solid fraction (SOL) (from particle) were determined from dilute exhaust particles collected on 47 mm Teflon-coated woven glass fiber filters. Coincidentally, particles were collected on 508 x 508 mm Teflon-coated non-woven glass fiber filters, and vapor-phase samples were collected on XAD-2 resin. The SOF and VOC for chemical and biological characterization were obtained by Soxhlet extraction of samples with dichloromethane (DCM). Hydrocarbon mass balances were developed to evaluate the efficiency of the sampling system. Use of the ceramic traps caused no change in engine total hydrocarbon (HC) levels at Mode 4 but decreases in TPM, SOF, and NO2 were noted. In terms of HC emissions only, the percentage of SOF was significantly reduced, but the percentage of VOC was unchanged. For Mode 5, the engine HC levels were significantly reduced but the proportions of HC components, i.e. the percentage of SOF and the percentage of VOC, did not change significantly. Engine emission levels of TPM, SOF, and nitrogen dioxide (NO2) were also significantly reduced at Mode 5. At both Modes 4 and 5, use of the ceramic particle traps caused an increase in the direct-acting (TA98) mutagenicity (revertants/microgram) of the SOF and a decrease in the activity of the VOC. The traps caused a 70 percent reduction of TPM at Mode 4 but only a 45 percent reduction in particulate-associated direct-acting mutagenicity on the basis of raw exhaust emissions (kRevertants/m3). At Mode 5 with the traps, there was an 85 percent reduction in TPM and only a 25 percent reduction in the activity of the SOF. The direct-acting mutagenicity of the VOC was reduced by use of the traps by 40 and 65 percent (kRevertants/m3) for Modes 4 and 5, respectively. In contrast, the indirect-acting mutagenicity of the Mode 4 VOC increased nearly 150 percent. Filter loading and reexposure experiments indicated that sampling artifacts did not contribute to the SOF mutagenicity at Mode 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceramics↗
PubMed1986

Neuroendocrine, biogenic amine and behavioral responsiveness to a repeated foot-shock-induced analgesia (FSIA) stressor in Sprague-Dawley (CD) and Fischer-344 (CDF) rats.

The neurobehavioral responsiveness of two strains of rats, Fischer-344 (CDF) and Sprague-Dawley (CD), to a repeated foot-shock-induced analgesia (FSIA) stress was compared in this study. Rats were either restrained or freely moving during shock presentation (sham controls were exposed to the shock environment only). The foot-shock (15-s, 1.5-mA scrambled electric shock) was observed to induce analgesia in the CDF, but not the CD strain following acute presentation; analgesia was evaluated using time for tail-withdrawal from hot water (55 degrees C). Both strains exhibited an analgesic response when latency to tail withdrawal was evaluated just prior to daily FSIA presentations over 15 total sessions indicating that these rat strains were behaviorally conditioned to this repeated stressor. However, the levels of conditioned analgesic responses to foot-shock were: greater in the CDF and most evident when rats were restrained on the shock-grid while being administered the foot-shock. All rats were quickly sacrificed following the 15th conditioning session to determine the effects of this stressor on neurotransmitter and neuroendocrine function in both strains of rat. Experimental subjects were exposed to the shock grid but not shocked during this last session. The following was found: plasma corticosterone (CORT) and prolactin levels and adrenal CORT levels were significantly increased by repeated stress in the CDF strain; only plasma CORT levels were elevated in the CD rat; pituitary immunoreactive beta-endorphin levels were significantly higher (+46%) amongst all experimental groups in the CDF strain, but stress was not observed to alter peptide steady-state levels in either strain; dopamine (DA), 5-hydroxytryptamine and metabolites (5-hydroxyindoleacetic acid and dihydroxyphenylacetic acid) levels were generally higher in the hypothalamus and frontal cortex of the CDF rat but turnover rates (implied from metabolite/amine ratios) indicated that these systems were more sluggish in this rat strain; hypothalamic DA turnover was significantly attenuated by repeated FSIA + restraint in both strains, but the dynamics of this effect appeared to be different between rat strains; and frontal cortex 5-HT turnover was significantly elevated by repeated FSIA + restraint in only the CDF rat. This research indicates that the CDF rat is extremely sensitive to an acute FSIA stress and it is less able than the CD rat to adapt to repeated presentation of this stress.

Adrenal Glands↗
PubMed1986

Determination of sodium caprylate in plasma volume expanders by gas chromatography.

A quantitative gas chromatographic method for the determination of the sodium (caprylate) octanoate, antimicrobial in the plasma volume expanders hydroxyethyl starch and human serum albumin, has been developed. The sodium caprylate and the internal standard were converted to pentafluorobenzyl derivatives. The reaction mixture was extracted with methylene chloride and chromatographed on a 1.8-m OV-17 column at 170 degrees C with flame ionization detection. The method is linear over the concentration range studied (40-700 micrograms/ml). The method is precise (coefficient of variation less than 2%).

Caprylates↗
PubMed1986

Comparison of two dosing schedules of flurbiprofen for patients with rheumatoid arthritis. Twice-daily versus four-times-a-day schedules.

A total daily dose of 200 mg of flurbiprofen (Ansaid, Upjohn) was administered either twice daily (100 mg BID) or four times daily (50 mg QID) to 143 patients with rheumatoid arthritis. Results of this 12-week, randomized, double-blind study showed statistically significant reductions in the number of swollen joints, number of affected joints, duration of morning stiffness, and 50-foot walk time in patients receiving either treatment regimen. Using standard statistical tests, no significant differences between regimens were found. Flurbiprofen treatment was rated as "excellent" or "good" by approximately half of the patients and physicians following both BID or QID dosing.

Adolescent↗
PubMed1986

Flurbiprofen versus naproxen in the treatment of rheumatoid arthritis.

The efficacy and safety of flurbiprofen (Ansaid, Upjohn), 100 mg twice daily, were compared with those of naproxen, 250 mg twice daily, in a six-week, double-blind, randomized study involving 133 patients with rheumatoid arthritis. Patients completing the six-week treatment phase were then treated with flurbiprofen, 100 mg twice daily, during a six-week open-label phase. In the double-blind phase, both treatment groups showed improvement from baseline and, in general, the arthritic condition of all patients was significantly less severe while receiving treatment. In the open-label phase, the patients in whom therapy was switched from naproxen to flurbiprofen reported greater improvement compared with baseline than they did at the end of the double-blind phase. Statistically significant differences between medication groups were few. At weeks four and six, grip strength for the naproxen group increased from baseline by a marginal amount compared with the flurbiprofen group. Global evaluations of disease improvement by patients and physicians and proximal interphalangeal joint size showed trends in favor of flurbiprofen. In the double-blind phase, 29.4 percent of flurbiprofen-treated patients (n = 20) and 23.1 percent of naproxen-treated patients (n = 15) experienced side effects, most of which were gastrointestinal in origin. In the open-label phase, 81.0 percent of the patients (n = 87) satisfactorily completed the six weeks of flurbiprofen treatment. Based on this study, 100 mg of flurbiprofen administered twice daily was as effective as 250 mg of naproxen twice daily in the treatment of rheumatoid arthritis.

Adolescent↗
PubMed1986

Double-blind comparison of flurbiprofen and sulindac for the treatment of osteoarthritis.

In this double-blind, randomized trial involving 143 patients with osteoarthritis of the hip and/or knee, the efficacy and safety of twice-daily dosing with flurbiprofen (Ansaid, Upjohn), which has a half-life of 5.5 hours, were compared with those of sulindac, which has a half-life of 7.8 hours. Patients were treated with flurbiprofen (50 mg orally twice a day) or sulindac (150 mg orally twice a day) for six weeks. Based on evaluations by both patients and physicians, there were no statistically significant differences between the two treatment groups in most of the efficacy parameters studied. In addition, there were no statistically significant differences between the two treatment groups in the incidence or type of side effects, which were primarily gastrointestinal in origin. This study indicates that flurbiprofen, taken as 50 mg twice daily, is equally as effective as 150 mg of sulindac twice a day in the treatment of osteoarthritis.

Adult↗
PubMed1986

Reversal by estrogen of the effect of dorsal raphe stimulation on release of LH but not prolactin.

Electrical stimulation of the dorsal raphe nucleus (DRN) was administered to rats 2-4 weeks after ovariectomy and at least 7 days following implantation of a bipolar electrode. During stimulation the concentration of luteinizing hormone (LH) decreased whereas that of prolactin (Prl) increased in serial plasma samples obtained from the unanesthetized animals via a cannula chronically implanted in the right external jugular vein. Administration of estradiol benzoate (5 micrograms/100 g BW) for 2 days prior to the experiment reversed the effect of stimulation on LH but augmented the Prl response, suggesting modulation by estrogen of the relative effectiveness of opposing pathways ascending from DRN to influence LH release. It is also apparent that LH and Prl release are controlled by distinct mechanisms since estrogen exerted opposite influences on the responses of these two hormones to stimulation of DRN.

Animals↗
PubMed1986

Loss of insulin response to glucose but not arginine during the development of autoimmune diabetes in BB/W rats: relationships to islet volume and glucose transport rate.

The insulin and glucagon responses to 10 mM glucose and 10 mM arginine were studied in pancreata isolated from nondiabetic diabetes-prone and diabetes-resistant BB/W rats at 60, 80, and 140 days of age and in diabetic BB/W rats on the 1st and 14th days of their diabetes. In the former group the insulin response to glucose declined progressively with age (r = -0.575; P less than 0.01) and at 140 days was significantly below age-matched diabetes-resistant controls (P less than 0.05). The insulin response to arginine did not decline with age in either group. For diabetic rats, on the first day of the diabetes, the insulin response to glucose was absent but the response to arginine did not differ from nondiabetic controls. On day 14 responses to glucose and arginine were both absent. The glucagon response to arginine showed no trend despite a decline in baseline glucagon secretion. Endocrine tissue in nondiabetic diabetes-prone rats made up 0.8 +/- 0.2% of the pancreas at 60 days of age and 0.52 +/- 0.22% at 140 days of age; the latter was significantly less than in 140-day-old diabetes-resistant controls (P less than 0.05). In diabetic rats on the 1st and 14th days of diabetes endocrine tissue was 0.2 +/- 0.1% and 0.07 +/- 0.02%, respectively. The glucose transport rate in islets isolated on the first day of diabetes was profoundly reduced compared to age-matched nondiabetic diabetes-prone controls. Thus, a population of arginine-responsive, glucose-unresponsive islets with low glucose transport rates is present at the onset of overt diabetes in BB/W rats.

Age Factors↗
PubMed1986

Extrarenal potassium adaptation: role of skeletal muscle.

Following the ingestion of a high-potassium-content diet for only a few days, the plasma potassium of rats rises only modestly in response to a previously lethal dose of potassium salts. This acquired tolerance, termed potassium adaptation, is principally the result of increased capacity to excrete potassium into the urine. However, a substantial portion of the acute potassium dose is not immediately excreted and is apparently translocated into cells. Previous studies have failed to show an increase in the content of potassium of a variety of tissues from such animals. Using 86Rb as a potassium analogue, we have shown that the skeletal muscle of potassium-adapted rats takes up significantly greater amounts of potassium in vivo in response to an acute challenge than does that of control animals. Furthermore, the same animals exhibit greater efflux of 86Rb following the termination of the acute infusion. We have also shown that the Na+-K+-ATPase activity and ouabain-binding capacity of skeletal muscle microsomes are increased by the process of potassium adaptation. We conclude that skeletal muscle is an important participant in potassium adaptation and acts to temporarily buffer acute increases in the extracellular concentration of potassium.

Adaptation, Physiological↗
PubMed1986

Evidence for multiple serotonergic influences on LH release in ovariectomized rats and for modulation of their relative effectiveness by estrogen.

Both opiates and serotonin (5HT) are known to inhibit LH release in ovariectomized rats, and estrogen has been shown to reverse certain serotonergic effects. Therefore studies were undertaken to compare the effects of morphine and the serotonin agonist 5-methoxy-N,N-dimethyltryptamine (5MEODMT) on LH release in ovariectomized rats with and without estrogen priming. Serial blood samples were collected via jugular cannulae before and 5, 15, 30 and 60 min after intravenous administration of morphine, 5MEODMT or both to rats receiving no pretreatment, or a serotonin receptor antagonist (methysergide, METH; or ketanserin, KET) 60 min earlier. In the absence of estrogen, morphine inhibited LH release, and the response was delayed by METH or abolished by KET, suggesting mediation by serotonin2 (5HT2) receptors. 5MEODMT alone failed to alter the release of LH significantly, but apparently activated both stimulatory and inhibitory serotonergic systems. Blockade of 5HT2 receptors with KET enabled an inhibitory system to prevail. No significant changes in LH concentrations were observed following combined administration of morphine and 5MEODMT. Similarly, in estrogen-primed rats morphine appeared to activate both inhibitory (5HT2) and stimulatory (5HT1) systems, resulting in no net change unless the inhibitory system had been antagonized by KET. Administration of 5MEODMT alone or in combination with morphine resulted in a strong stimulatory effect which appeared to be mediated by 5HT1 receptors. These results suggest the existence of a multiplicity of serotonergic influences on the release of LH in the rat, not only in terms of particular species of 5HT receptors, but also in neuronal connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

SQ 30,957, a new antibiotic produced by Penicillium funiculosum. Taxonomy, fermentation, isolation, structure determination, synthesis and antibacterial activity.

A new antibiotic, SQ 30,957, 4-diazo-3-methoxy-2,5-cyclohexadien-1-one, has been isolated from fermentation broths of Penicillium funiculosum. The structure (1) was deduced from its spectroscopic properties and its degradation reaction. SQ 30,957 has excellent activity against anaerobic bacteria such as Clostridium and Bacteroides and has moderate activity against aerobic bacteria. The compound has an LD50 of less than 17 mg/kg in mice by intraperitoneal administration.

Animals↗