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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 505 records · Page 28Linked to original sources

Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis?

In a multicenter, double-blind, parallel-group study, 233 patients with classical or definite RA who demonstrated disease flare during a prestudy washout period were randomized to 12 weeks of treatment with either the nonacetylated salicylate, salsalate (salicylsalicylic acid), or aspirin. Of the 150 patients who completed the study, 83 received salsalate and 67 were treated with aspirin. Doses of the two drugs were calculated to provide equal amounts of bioavailable salicylic acid. The efficacy of salsalate and aspirin, as measured by all the usual variables, was equivalent but aspirin-treated patients had a higher incidence of severe gastrointestinal problems. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the anti-inflammatory efficacy of salicylic acid in RA.

Anti-Inflammatory Agents, Non-Steroidal↗

Renal replacement therapy in the ICU: the role of continuous arteriovenous haemodialysis.

Conventional haemodialysis is not available on all intensive care units (ICUs) and there are relatively few renally trained nurses able to run haemodialysis machines. Continuous arteriovenous haemodialysis provides effective renal replacement therapy for critically ill patients in the ICU. Unlike continuous arteriovenous haemofiltration it provides sufficient control over electrolyte, solute and water balance to obviate the need for additional treatment with intermittent conventional haemodialysis.

Acute Kidney Injury↗

Differences in the pattern of proliferative response with age in thymocytes undergoing spontaneous and induced proliferation.

The proliferative capacity of thymocytes from C3H/HeJ mice decrease as the animals attain maturity. The proliferative response of thymocytes from 24- to 28-week-old mice to stimulation with concanavalin A (Con A) is only 20% of that observed at 4 weeks of age. The decreased proliferative capacity of thymocytes in response to Con A stimulation observed between 4 and 24 weeks of age closely correlates to the drop in thymic weight and cellularity observed during this period. In contrast, the spontaneous proliferative capacity of thymocytes, as well as proliferation of thymocytes in response to stimulation with phorbol myristate acetate (PMA) and ionomycin, drops only slightly during this period, as proliferation under these condition in thymocytes from 24- to 28-week-old mice is approximately 65-70% of that observed in 4-week-old animals. We have previously shown that cytoplasmic extracts from proliferating lymphoid cells contain a factor, termed the activator of DNA replication (ADR), which is capable of inducing DNA synthesis in isolated, quiescent nuclei. We show in this study that the decreased proliferative capacity of thymocytes during whole organism maturation and thymic involution is associated with decreased endogenous levels of ADR, while nuclear sensitivity of thymocyte to ADR was retained during these process. The diminution of ADR activity during thymic involution was quantitatively greater than the loss in proliferative capacity.

Aging↗

Protection of cattle from infection with vaccinia virus by bovine interferon alpha C.

The efficacy of bovine interferon alpha C as an antiviral compound was evaluated in calves infected with vaccinia virus. Calves treated with the interferon did not develop characteristic vaccinia lesions, demonstrating a clear protective effect of treatment. The only side effect observed was hyperthermia. After intramuscular injection, interferon appeared quickly in the blood and was cleared within 24 hours. The in vivo antiviral activity of bovine interferon alpha C was confirmed by its ability to induce 2'5' A synthetase, an enzyme implicated in the antiviral state, in lymphocytes.

2',5'-Oligoadenylate Synthetase↗

The EGF receptor kinase substrate p35 in the floor plate of the embryonic rat CNS.

P35 is a calcium- and phospholipid-binding protein that was originally isolated as a substrate for the epidermal growth factor (EGF) receptor tyrosine kinase and later was found to be related to lipocortin I. Immunohistochemistry was used to localize p35 to a raphe of primitive glial ependymal cells in the median one-third of the floor plate in the central nervous system (CNS) of rat embryos. The p35 appears by embryonic day 12 before the arrival of pioneering ventral commissural axons. The unexpected, discrete distribution of this protein during development opens the question of its role in neural morphogenesis.

Animals↗

Hepatectomy prolongs survival of mice with induced liver metastases.

Resection of hepatic metastases from colorectal cancer has been shown to prolong survival in some patients. Whether this results from a reduction of tumor burden or is an indirect effect mediated by hepatectomy is questionable. Male C57BL/6Ros 8-week-old mice underwent ileocolic vein injection of a suspension of 0.3 mL of 2 x 10(5) viable liver-derived murine (MCA-38) colonic adenocarcinoma cells. This model produces hepatic metastases in all lobes of the liver. At 7, 14, or 21 days after tumor injection, mice were randomized to receive either 42% resection of the liver or laparotomy alone. Survival in the animals with hepatectomy was significantly prolonged when the hepatectomy was performed 14 or 21 days after tumor injection.

Animals↗

Lipocortin I (p35) is abundant in a restricted number of differentiated cell types in adult organs.

Lipocortin-I (p35) is a unique calcium- and phospholipid-binding protein of the lipocortin/calpactin family. Although several possibilities have been suggested, functions for the individual proteins of this family are not yet known with certainty. As an initial step in the identification of the biological function(s) of p35, we have used immunohistochemical methods to define precisely many of the cellular phenotypes that contain p35 in vivo. In all organs where p35 is found, we have observed a striking distribution of p35-positive cells. Typically it is highly enriched in a limited range of differentiated cell types while apparently totally absent from most others. Our identification of specific p35-positive cell types in vivo will now set limitations on likely possibilities for functions of this protein and thereby permit a more logical approach to the determination of its true function.

Animals↗

Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant.

A nonionic surfactant, diethyleneglycol lauryl ether (PEG-2-L), increases the flux of either theophylline or adenosine by a factor of 2.2-2.7, when these are delivered from propionic acid solutions into human skin samples, with respect to propionic acid alone. At the same time, the flux of propionic acid from the same vehicles is decreased. Significant expansion of the partial molal volumes vi of both purines occurs following incorporation of PEG-2-L into their propionic acid solution. Hence, the enhancing effect of this surfactant arises mainly from an increase in the excess free energy of these solutes in the donor phase ("push" effect). Paraffin oil increases the flux of either drug from propionic acid by an entirely different mechanism. It enhances the flux of propionic acid into the skin, thus promoting the partitioning of the purine solute in the modified skin barrier ("pull" effect). Indeed, the magnitude of vi of either purine in propionic acid:paraffin oil solution gives no indication of a significant interaction between paraffin oil and the purine solute. Finally, the penetration enhancing effects of PEG-2-L and paraffin oil combined together in the same propionic acid vehicle are additive, resulting in a flux which is approximately the sum total of fluxes obtained separately with PEG-2-L or paraffin oil.

Adenosine↗

Colonic slow-wave analysis. Limitations of usefulness of fast Fourier transform (FFT).

The fast Fourier transform (FFT) has been used to determine frequency components of colonic slow-wave activity. We studied the effect of (1) recorder filter characteristics, (2) number of data points and, (3) data window overlap technique and ingestion of a 1000-kcal meal on the resulting power spectrum. Human rectosigmoid slow-wave activity was recorded in nine normal subjects and stored on FM tape for computer analysis. The dynograph filter characteristics were tested using square wave signals, and derived compensation factors were applied to the FFT before viewing. The dynograph filter, when set to optimize visualization of slow waves, attenuates low frequencies nonlinearly. Failure to compensate for the dynograph filter results in inaccurate detection of slow-wave frequencies. FFT of 1-min data gives a different power spectrum than an FFT of 4 min data, indicating a rapidly changing waveform. FFT's of 1 min of data when examined over time fail to demonstrate a consistent frequency spectrum, confirming this conclusion. The lower frequencies in the normal human rectosigmoid are present at the greatest power. These studies indicate that the colon has slow waves of irregular frequencies, in contrast to the stomach or small intestine. No change in the dominant frequency was seen following the ingestion of a 1000-kcal meal.

Adult↗

Vasoactive intestinal peptide. An inhibitor of feline gastric smooth muscle in vitro.

Dose-response characteristics of feline corpus circular muscle were studied in vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10(-8) M or 10(-7) M vasoactive intestinal peptide (P less than 0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to greater than or equal to 10(-6) M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P less than 0.001) and reduced responses to substance P (P less than 0.05), but had no effect on responses to cholecystokinin-octapeptide (P greater than 0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.

Animals↗

Tacrine or arecoline mediates reversal of anoxia- or AF64A-induced behavioural disorders in the developing rat.

A 25 min anoxia, or an intracerebroventricular bilateral 2 nmol dose of ethylcholine aziridinium (AF-64A), administered postnatally to male rat pups, elicited on further development of these behavioural disorders, which are partly related to central cholinergic hypofunction. These included a hyperkinetic syndrome and inferior performance in the passive avoidance test. The anoxia-lesioned group but not the AF-64-A-lesioned one, showed an inferior performance in the active avoidance test. Administration of tacrine, an inhibitor of cholinesterase, or arecoline, a cholinergic agonist, in the drinking water to the nursing mothers, at an estimated daily dose of 15 and 10 mg/kg, then directly to the juvenile rats after weaning and until the age of 40 days, partly reversed the effects of anoxia or AF-64A, normalizing the level of locomotor activity and improving performance in passive avoidance, but not in active avoidance. These beneficial effects persisted long after discontinuation of administration of either drug, suggesting that stimulation of spared cholinoceptors in brain at development had prompted the recovery of cholinergic function.

Animals↗

A benzodiazepine receptor antagonist improves emergence of mice from halothane anaesthesia.

The benzodiazepine receptor antagonist, flumazenil, at a dose of 10 mg/kg given intraperitoneally to mice, had no effect on the minimum air concentration (MAC-50) of halothane causing anesthesia in 50% of the animals and which was 1.0% by volume of the inhaled air. Diazepam, 10 mg/kg, potentiated the effect of halothane. When the mice had been pretreated with diazepam and flumazenil, 10 mg/kg or 20 mg/kg, partial but not complete reversal of the potentiating effect of diazepam was observed, minimum air concentration values being 0.6% after diazepam alone and 0.8% after diazepam and flumazenil. However, mice pretreated intraperitoneally with flumazenil, in the concentration range 1-10 mg/kg, delivered as a solution in polyethylene glycol-Intralipid vehicle or as a suspension in saline, recovered control levels of spontaneous motor activity much faster than in the absence of flumazenil, on emergence from halothane-induced anaesthesia. In this range, the effect was not dose-dependent. These findings suggest that some of the effects of halothane are mediated at the level of the benzodiazepine receptor.

Anesthesia↗

Inhibition of thymocyte mitogenic responses by coculture with thymic epithelial cells.

We have previously reported the isolation and culture of two morphologically distinct types of murine thymic epithelial cells (TECL and TECs) and have studied their capacity to produce soluble factors as well as to bind thymocytes in vitro. In the present study, we examined whether direct interactions of thymic epithelial cells with thymocytes regulate thymocyte function by studying the effect of these thymic epithelial cell lines on thymocyte responses to mitogen. We found that direct contact between thymocytes and epithelial cells markedly suppresses both thymocyte and splenocyte responses to mitogen. This effect is irreversible after a 24-hr incubation on thymic epithelial cells, is not H-2 restricted, and appears to be epithelial cell specific. The inhibitory effect is mediated by a molecule or molecules present constitutively on the plasma membrane of epithelial cells. One mechanism of inhibition involves the generation of suppressor cells on contact of thymocytes with thymic epithelial cells or cell membranes. However, it is also possible that molecules with direct immunosuppressive activity may be present on these cell membranes.

Animals↗