Search PubMed⌕ Search

Biomedical subjects

S L Cohen

Publications and source records attributed to S L Cohen.

At least 73 records · Page 4Linked to original sources

A pharmacological examination of the resistance-to-change hypothesis of response strength.

The effects of d-amphetamine sulfate, sodium pentobarbital, haloperidol, and cholecystokinin-octapeptide were examined within the context of Nevin's (1974, 1979) resistance-to-change hypothesis of response strength. In three experiments, rats' responding was reinforced by delivery of food under chained random-interval 30-s random-interval 30-s, multiple fixed-interval 30-s fixed-interval 120-s, or multiple random-interval 30-s random-interval 120-s schedules. Each rat received several doses of each drug and changes in response rate were measured. The resistance-to-change hypothesis predicts greater disruption of response rate relative to baseline in the initial component of the chained schedule and in the 120-s component of the multiple schedules. In the chained schedule cholecystokinin-octapeptide produced greater reductions in response rate relative to baseline in the initial component. However, no differences between components were observed with haloperidol or sodium pentobarbital, and high doses of d-amphetamine reduced response rate in the terminal component relatively more than in the initial component. In the multiple schedules either no differences were observed between components or response rate was reduced more relative to baseline in the 30-s component. The data fail to support the notion that drugs may be viewed within the same context as other response disruptors such as extinction, satiation, and the presentation of alternative reinforcement.

Animals↗

A comparison of peripheral and central effects of CCK8 on water-reinforced operant responding.

Systemic administration of cholecystokinin-octapeptide (CCK8) suppresses operant responding in water deprived rats, but it is unclear whether this effect is centrally or peripherally mediated. Rats were trained to press a lever for water in an operant conditioning chamber under a variable-interval schedule of reinforcement. After response rate stabilized injections were administered, and response suppression was measured by comparing injection response rate to baseline rate. Intracerebroventricular injections of CCK8 reduced lever pressing at relatively high doses (20 and 50 micrograms/rat). But in a direct comparison, the same dose of CCK8 (20 micrograms/rat) given intraperitoneally reduced responding significantly more than when given into the lateral ventricle. The suppressive effects of CCK8 (30 and 300 micrograms/kg i.p.) were significantly reduced by complete abdominal vagotomy. The effects of CCK8 (30 micrograms/kg i.p.) were blocked by pretreatment with the specific competitive CCK8 antagonist dibutyryl cyclic GMP (70 and 140 mg/kg i.p.), but not by the acetylcholine antagonist atropine (0.1 to 10 mg/kg i.p.). These data suggest that suppression by CCK8 of operant lever pressing in water-deprived rats is primarily mediated by vagal afferent fibers.

Animals↗

A function for estriol during human pregnancy--a hypothesis.

It has been hypothesized that large amounts of estriol (E3) are produced during human pregnancy to ensure a quiescent uterus during prelabour pregnancy by combining with most of the myometrial nuclear receptors, leaving an inadequate number for a stimulatory estradiol (E2) concentration. It is further hypothesized that the amount of E3 formed is controlled by the amount of E2 present. During labour this control is lost, which together with an increased E2 (plus or minus a simultaneous drop in E3) production permits labour. Two of the seven pieces of evidence offered in support of this hypothesis were carried out in the author's laboratory. These are: 1. Urinary assays by two methods, one for total estrogens and one for the fractionated classical estrogens revealed that while the ratio (formula; see text) varies from patient to patient, for any one patient it remains markedly constant, especially during the second half of pregnancy. 2. Pieces of myometrium removed at cesarean delivery and assayed for their nuclear estrogen content revealed an E3/E2 ratio of 1.7 when the cesarean was an elective one (and therefore with a quiescent uterus) but reduced to 0.65 when the cesarean was performed after labour had started. The relationship between these two pieces of evidence and five from the literature with the hypothesis are discussed.

Estradiol↗

The systematic use of semantic and acoustic processing by younger and older adults.

To examine age differences in semantic and acoustic processing, 80 older and 80 younger adults participated in an incidental learning study. The study compared free recall and semantic and acoustic cued recall performance after five orienting conditions. The younger adults performed better than the older adults, especially after acoustic orienting. Encoding specificity effects occurred at both age levels. The results indicated that both age groups performed better with semantic processing than acoustic processing, but that older adults relied on the semantic information far more than the younger adults.

Adult↗

Lupus-like nephritis heralding the definitive manifestation of systemic lupus erythematosus.

Four patients presented with the nephrotic syndrome. The histological appearances on renal biopsy were in three characteristic and in one suggestive of lupus nephritis. These patients did not initially have other clinical features of SLE, but three had a positive ANA and one a raised DNA titre. Remission occurred in two patients, in one spontaneously and in another following corticosteroid therapy, but two developed renal failure. During follow-up all developed elevated DNA binding levels and arthralgia or lymphopenia. The ARA classification criteria for lupus were only fulfilled at this late stage.

Adult↗

Thymoma presenting as a middle mediastinal mass.

A case of a middle mediastinal mass which proved to be a thymoma is presented. The diagnostic difficulties that middle mediastinal masses produce and the investigations used to delineate them are discussed.

Humans↗

Abnormal excretion of oestrogens in complicated pregnancies.

The tremendous interpatient variations that occur for oestrogen excretion during pregnancy are largely overcome by expressing results in terms of relative concentrations (i.e., as percent of total oestrogens excreted). Specimens of urine from 28 pregnant patients with a variety of complications were assayed for their oestrogen content by an "oestrogen profile" technique and the results thus expressed were compared with those from 20 normal pregnancies. Statistically significant changes are shown in the group of patients in the "above" normal range (normal range = normal mean +/- 3 X SE) for five oestrogens (oestrone, 2-hydroxyoestrone, 2-methoxyoestrone, 2-hydroxyoestradiol, and 2-hydroxyoestriol) and "below" the normal range for one oestrogen (oestriol). When the means of the oestrogen values for the different groups of patients were examined, two things became obvious; firstly, only patients with hypertension showed these changes, and secondly, two additional oestrogens (16-hydroxyoestrone and 16-epioestriol) were excreted in large amounts by the normotensive "high risk" patients. A comparison of the two methods of expressing oestrogen assay results is made quantitatively (as milligrams per day) versus relatively (as percent of total oestrogens excreted), and advantages and disadvantages of each are discussed.

Diabetes Mellitus↗

Treatment of chronic renal failure with dietary fiber.

We have tested the hypothesis that dietary fiber, by inhibiting colonic bacterial ammonia generation and increasing fecal nitrogen excretion, might decrease hepatic urea synthesis and thereby reduce plasma urea in patients with chronic renal failure. Six and 8 week courses of two different hemicelluloses, arabinogalactan and ispaghula, reduced mean plasma urea in uremic subjects by 11% and 19% respectively. Ispaghula also reduced the rate of rise of plasma creatinine to zero and, in one formal balance study, increased fecal nitrogen excretion by 39%. Experiments in vitro showed that ispaghula depressed anaerobic fecal bacterial net ammonia generation by 30%, and adsorbed neither urea nor ammonia. The reduction in plasma urea caused by dietary fiber is likely to be due to inhibition of colonic bacterial production of ammonia; such therapy could conceivably alleviate some of the symptoms of uremia and postpone dialysis in patients with endstage renal disease.

Adolescent↗

Minimized tolerance to the suppressive effects of CCK8 on operant responding.

This study was designed to determine if tolerance to cholecystokinin octapeptide (CCK8) could be prevented or minimized by spacing injections, and if an appetitive operant conditioning paradigm provides a sensitive baseline to test the effects of CCK8. Male Sprague-Dawley rats were trained to press a lever for water according to a fixed-interval 60-sec schedule of reinforcement. After response rate stabilized, rats were given a series of CCK8 (0.04 mg/kg, ip) injections spaced several days apart. The first injection of CCK8 produced complete response suppression during the 30-min test session, while later injections produced partial or complete suppression. Thus, tolerance to CCK8, as measured by operant response rate, may be minimized if injections are appropriately spaced.

Animals↗

Nephrotoxicity of phenazopyridine.

A young man developed reversible acute renal failure after a large overdose of phenazopyridine. The renal failure was treated by peritoneal dialysis. Analysis of blood and urine samples failed to demonstrate the parent drug but a metabolite with similar ultraviolet absorption was detected. No parent drug or metabolites were detected in the peritoneal dialysate.

Adult↗

Sodium and potassium status, plasma renin and aldosterone profiles in normotensive and hypertensive Johannesburg blacks.

Many studies have suggested that there is an association between the sodium status, plasma renin and aldosterone profile and essential hypertension. We measured serum, urine and red blood cell (RBC) sodium and potassium, plasma renin and aldosterone levels in normotensive Whites, normotensive Blacks, mildly hypertensive Blacks, severely hypertensive Blacks and Blacks with malignant hypertension. There were no important differences between the groups studied as regarded the serum sodium, serum potassium and urinary sodium excretion values. However, the urinary potassium excretion was significantly lower in normotensive and hypertensive Blacks than in Whites. RBC sodium concentrations showed no significant differences in the mean values across the range of degrees of hypertension in Blacks, although they tended to be higher in the more severely hypertensive groups. Blacks with mild-to-moderate hypertension as well as the severely hypertensive group had significantly lower plasma renin levels than the normotensive group; only in the malignant hypertensives with advanced renal failure did the plasma renin and aldosterone levels rise.

Adult↗

Cholecystokinin-octapeptide effects on conditioned-avoidance behavior, stereotypy and catalepsy.

The effect of peripherally administered cholecystokinin-octapeptide (CCK8) was tested on signaled-avoidance behavior, apomorphine-induced stereotypy, and catalepsy. Rats were trained to avoid shock in a signaled shuttle-box avoidance task, and then given CCK8, tetragastrin, or haloperidol. CCK8 (20-3840 micrograms/kg i.p.) reduced avoidance in a dose-dependent manner. The impairment at maximal dose levels was approximately 25% from its predrug level compared to 50% with haloperidol (100 micrograms/kg i.p.). Combined injection of CCK8 (320 micrograms/kg i.p.) and haloperidol (75 micrograms/kg i.p.) reduced avoidance significantly more than either drug alone. The effects of CCK8 were relatively brief in that active avoidance was impaired if CCK8 was injected up to 15 min before the avoidance test. CCK8 also facilitated the extinction of avoidance. Tetragastrin (177 micrograms/kg i.p.), which elicits gastrointestinal effects resembling CCK8, did not affect avoidance. In addition, CCK8 diminished apomorphine-induced stereotypy up to 5 min after CCK8 injection. CCK8 (20-1280 micrograms/kg i.p. and s.c.) failed to produce catalepsy in vertical grip tests. These data suggest that peripherally administered CCK8 has sedative and certain neuroleptic-like effects on behavior.

Animals↗

Effects of septal lesions on the discrimination of fixed-ratio performance.

Rats with septal lesions and control rats were required to press the center lever of a three lever operant chamber a fixed number of times before activating the side levers. If the rat pressed the center lever 32 times, then a response on the right lever was correct and food was delivered. If the rat pressed 2, 4, 8, or 16 times on the center lever, then a response on the left lever was correct. Both groups were able to discriminate between long and short fixed-ratio schedules. As expected, more errors were made as the discrimination became more difficult. Septal rats, however, were unable to discriminate as well as control rats. These data suggest that septal lesions interfere with rats' ability to monitor response-produced proprioceptive stimuli.

Animals↗

The changing estrogen content of the nuclear fraction of human myometrium during labor.

The cytosol and nuclear fractions were prepared from 32 pieces of myometrium obtained from 20 elective cesarean sections (regarded as typical of quiescent pregnancy (P)) and 12 emergency cesareans (performed after labor had started and therefore taken as typical of labor (L)). The nuclear fraction was purified by standard procedures. All protein-bound estrogen was released from the nuclear fractions, and the released estrogen simultaneously solubilized by denaturation with ethanol. The estriol (E3) and estradiol (E2) content of the alcohol solutions were assayed by radioimmunoassay with highly specific antisera for E3 and E2. In the L group, average E3 content was slightly (not significantly) lower, and average E2 content was significantly (P less than 0.005) higher, than in the P group. The E3/E2 ratio decreased dramatically (P less than 0.001) during this change from P to L.

Cell Nucleus↗

Cyclosporin A for the treatment of systemic lupus erythematosus.

Cyclosporin A (CyA) was given to five patients with active systemic lupus erythematosus (SLE) at a dose of 10 mg/kg/day orally. No patient was able to take the drug for longer than seven weeks because of side effects including nephrotoxicity. Angio-oedema was noted in three patients and serum C1 esterase inhibitor levels were shown to be depressed in four out of five patients whilst taking CyA. Two patients did experience an improvement in their arthralgia but given the side effects induced we cannot, at present, recommend CyA for the treatment of SLE.

Adult↗