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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 559 records · Page 31Linked to original sources

Effect of apamin on local rates of glucose utilization in the brain and the spinal cord in rats.

The effects of apamin on local rates of glucose utilization in the brain and spinal cord were studied employing the quantitative autoradiographic deoxyglucose method. Forty-five to 60 min after administration of apamin the animals lost exploratory behavior, remaining completely immobile, with the 4 limbs overextended, unresponsive to auditory stimuli. Out of 30 neural structures examined, glucose utilization was significantly decreased in the cochlear n., superior olivary n., lateral lemniscus, inferior colliculus, medial geniculate body, fastigial n., globus pallidus, caudate-putamen, n. accumbens and the lumbar ventral horn of the spinal cord. These results show that apamin specifically affects the functional activity of the auditory and motor structures.

Animals↗

Behavioral differences in the developing rat following postnatal anoxia or postnatally injected AF-64A, a cholinergic neurotoxin.

Rat pups were submitted postnatally to one of two procedures: a 25-min exposure to 100% nitrogen or an i.c.v. bilateral injection of AF-64A, 2 nmol contained in 1-microliter saline. Throughout further development of either group, their performance in passive and active avoidance tests and in amphetamine-induced stereotype behavior was followed and compared. Both groups exhibited hyperactivity which persisted until 42 days of age in the anoxia group and beyond 120 days in the AF-64A group. Both groups were equally inferior to controls in the passive avoidance test, but only the anoxia group was inferior to controls in the active avoidance test. Amphetamine-induced stereotype behavior was much less pronounced in the anoxia group relative to AF-64A-treated rats or to controls. The results suggest that the lesion induced by the neurotoxin is more specific and less widespread than the one caused by anoxia.

Animals↗

Randomized surgical adjuvant trial of interferon alfa-n1 in recurrent papillomatosis.

Sixty-six patients with recurrent respiratory papillomatosis of juvenile onset were treated for six months with interferon alfa-n1 (Wellferon) in a randomized crossover trial. Half received interferon alfa-n1 intramuscularly at a dosage of 5 megaunits per square meter daily for 28 days and then thrice weekly for five months, followed by six months of observation. The other half were observed for six months and then treated. Operations were performed every two months to assess disease extent by a scale developed for this purpose. The score for the patients during the first observation period was stable. There was a statistically significant lowering of score in patients receiving interferon alfa-n1 during both periods of drug administration. Eight of 57 patients with assessable airway disease achieved complete remission, as did one additional patient with disease limited to the nasopharynx. No patients achieved complete remission during six months of observation alone. This difference was statistically significant. Patients without tracheostomy were significantly more likely to achieve remission than those with a tracheostomy. The patients who were observed after discontinuation of the drug therapy showed a significant rise in score within four months. Symptoms of toxicity included transient fever, fatigue, nausea, and headache. Elevations in serum aspartate aminotransferase levels occurred in 64% of the patients. There was an inverse correlation between age and the ability to tolerate the medication. The dose studied may be close to the maximum tolerated dose. It appears that interferon alfa-n1 as an adjuvant to routine surgical management is effective in slowing the growth of respiratory papillomas.

Clinical Trials as Topic↗

Three-dimensional structure of the regular surface glycoprotein layer of Halobacterium volcanii from the Dead Sea.

A three-dimensional reconstruction from electron micrographs of negatively stained cell envelopes of Halobacterium volcanii has revealed the structure of the surface glycoprotein to a resolution of 2 nm. The glycoprotein is arranged on a p6 lattice with a lattice constant of 16.8 nm. It forms 4.5 nm high, dome-shaped, morphological complexes with a narrow pore at the apex opening into a ;funnel' towards the cell membrane. The polarity of the structure was derived from freeze-etching experiments and ;edge' views. Six radial protrusions emanate from each morphological complex and join around the 3-fold axis to provide lateral connectivity. Using the primary structure of the surface glycoprotein of the closely related species Halobacterium halobium (Lechner and Sumper, 1987) and the cell envelope profile from a previous X-ray analysis of the same species (Blaurock et al., 1976) we have integrated our reconstruction into a model of halobacterial cell envelope.

Journal Article↗

Differentiation of HL-60 cells is associated with an increase in the 35-kDa protein lipocortin I.

Lipocortin I, a 35-kDa protein, has been detected in terminally differentiated monocytes and neutrophils. This calcium-phospholipid binding protein appears to be identical to a 35-kDa protein that can serve as a substrate for the EGF-receptor/tyrosine kinase. We have used the human myelocytic cell line HL-60 to explore whether differentiation of hematopoietic cells is associated with changes in the level of lipocortin I. We find that differentiation of HL-60 cells toward the macrophage lineage by the addition of phorbol esters or vitamin D3 or toward neutrophils with dibutyryl cyclic AMP or dimethyl sulfoxide is accompanied by an increase in the cellular content of lipocortin I. In comparison, treatment of HL-60 cells with bryostatin 1, a compound that activates protein kinase C but does not differentiate HL-60 cells, did not effect the level of 35 kDa protein. We have developed a radioimmunoassay to quantitate this protein by using a polyclonal antibody to a synthetic amino terminal peptide of the 35-kDa protein. This antibody recognizes purified pig lung 35-kDa protein as well as a single 35-kDa protein in HL-60 and A-431 cells as determined by Western blotting and immune precipitation. Differentiated HL-60 cells contain 2.6-fold the amount of 35-kDa protein found in undifferentiated HL-60 cells. Our findings that the addition of phorbol esters to HL-60 cells results in an increase in the mRNA for the 35-kDa protein and in an increase in the incorporation of 35S-methionine into the protein suggest that transcriptional activation or increased stability of the mRNA is responsible for the increased rate of synthesis and accumulation of lipocortin I during differentiation of these cells. In the absence of added divalent cations, we have determined that in differentiated HL-60 cells 79% of lipocortin I protein is located in the cytosol while 21% of the total cellular protein is bound to the particulate fraction. The 35-kDa protein can be removed from the particulate fraction by incubation with chelators or treatment with phospholipase A2 or phospholipase C. Addition of the calcium ionophore A23187 to intact differentiated HL-60 cells causes the 35-kDa protein to associate with the particulate fraction of the cell, suggesting that modulation of intracellular calcium levels may play a role in changing the intracellular location of this protein.

Annexins↗

Penetration of adenosine into excised human skin from binary vehicles: the enhancement factor.

Human skin samples are permeable to adenosine delivered from 0.5-3% solutions in vehicles consisting of propionic acid, hexanoic acid, or mixtures of these in various ratios. The observed optimal Kp, hence flux, of adenosine from the binary vehicles is 0.4 X 10(-3) cm/min, while that from propionic acid is 0.12 X 10(-3), and that from hexanoic acid is 0.16 X 10(-3) cm/min. The bell-shaped dependence of the observed Kp on donor vehicle composition may be resolved into two trends proceeding in opposite directions: an increase in the excess free energy of adenosine in the donor vehicle with an increase in volume fraction of hexanoic acid in that vehicle ("push" effect); and an increase in the flux of adenosine with an increase in the flux of propionic acid ("pull" effect) delivered from the binary vehicle. The Kp of adenosine anticipated from its excess free energy in the donor phase ("push" effect), independent of any enhancing effect due to the presence of propionic acid, is calculated from the partial molal volume of adenosine in a given vehicle; this volume correlates inversely with the solubility parameter of that vehicle. The ratio of the observed Kp to the calculated Kp gives an enhancement factor which is approximately 6 for a formulation consisting of four volumes of hexanoic acid and six volumes of propionic acid. A similar trend is found for binary vehicles of isopropyl myristate and propionic acid.

Adenosine↗

Evidence for a direct and indirect action of leucine enkephalin at the feline ileocecal sphincter.

An in vitro whole organ bath preparation was used to examine the effects of leucine enkephalin on the cat ileocecal sphincter (ICS) intraluminal pressure and myoelectric activity. The bath allowed separation of the bathing media surrounding the ICS and the ileum. Leucine enkephalin (2 x 10(-7) M) when added to the ileal bathing medium caused a delayed increase in ICS spike activity and pressure which was blocked by tetrodotoxin (10(-5)M). In contrast, leucine enkephalin (2 x 10(-7)M) added directly to the ICS bathing medium caused an immediate spike-associated contractile response which was tetrodotoxin-resistant. Thus both an indirect and direct opiate action at the ICS was demonstrated.

Action Potentials↗

The antihypertensive effect of ethylcholine aziridinium (AF64A), a cholinergic neurotoxin, in spontaneously hypertensive rats, following administration into the posterior hypothalamus.

The aim of this study was to ascertain whether drug-induced cholinergic hypofunction in the posterior hypothalamus would affect the development and the maintenance of hypertension in hypertensive rats. Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were treated with AF64A, a neurotoxin which can irreversibly inhibit cholinergic transmission in vivo. AF64A or saline was injected bilaterally into the posterior hypothalamus of rats of two age groups: normotensive one month-old rats whose blood pressure was subsequently measured at the age of three months and hypertensive three month-old rats, whose blood pressure was measured four weeks later. In both age groups there was a significant fall in mean arterial blood pressure in SHR but not WKY rats. In SHR injected at the age of one month, there was a fall of at least 15.9 mm Hg, while in the rats injected at the age of three months there was a fall of 14.3 mm Hg. Heart rate in either strain was not affected. When AF64A was injected into the anterior hypothalamus of one month-old SHR, no antihypertensive effect was observed in these rats at the age of three months. These results show that cholinergic stimulation in the posterior hypothalamus may play a role in both the development and maintenance of hypertension in SHR.

Animals↗

Characterization of the molecules involved in thymocyte thymic epithelial cell adhesion.

Cell to cell adhesion is important for mechanisms of cellular recognition, growth, and differentiation. The identification of molecules involved in these interactions is necessary in order to understand the molecular basis of these processes. We have previously described the development of two different thymic epithelial cell lines (TECS and TECL). Using an assay with radiolabeled thymocytes we found that thymocytes can adhere specifically to these thymic epithelial cells. This adhesion is trypsin sensitive, suggesting that involvement of specific cell surface proteins. In the present study we further characterize and begin identification of the molecules involved in this interaction. We found that thymocyte binding to thymic epithelial cells requires the presence of Ca2+ and Mg2+ and is mediated by a molecule greater than 10,000 MW. Also, we identified several antibodies which inhibit the adhesion of thymocytes to TECS. The membrane nature of the molecule mediating this interaction was confirmed by the ability of thymocyte membranes to block the inhibitory antibodies.

Animals↗

Hospitalization effect in acute mania.

We studied 31 patients meeting DSM-III criteria for bipolar affective disorder, manic type. All were treated in hospital, 18 on an open ward and 13 on a psychiatric intensive-care unit. Despite the use of only moderate doses of medication, dramatic clinical improvement was observed over the first 48 hours of treatment using the Brief Psychiatric Rating Scale and Beigel Mania Rating Scale as objective rating measures. Significantly greater improvement occurred in the psychiatric intensive-care unit in comparison to the open ward. We suggest that hospitalization effect is of prime importance in the early management of the acutely manic patient.

Adult↗

The cell wall structure of a magnesium-dependent halobacterium, Halobacterium volcanii CD-2, from the Dead Sea.

Cell wall preparations from the magnesium-dependent halophilic bacterium, Halobacterium volcanii, were studied by high-resolution electron microscopy complemented with image analysis and processing. For ultrastructural studies, specimens were prepared by a variety of methods, including negative staining, and metal shadowing after air-drying, freeze-drying, or freeze-fracturing and etching. All methods revealed the cell wall to be composed of a near-hexagonal lattice of unit cells having a center-to-center spacing of 15.5 nm. While negatively stained samples yielded two types variably revealed the unit cell to be composed of six protomers surrounding a central mass depression. This low-resolution unit cell morphology appears very similar to that of other bacterial cell wall S-layers studied to date.

Cell Wall↗

Effect of experimental cardioplegia methods on normal and hypertrophied rat hearts.

The purpose of this study was to evaluate whether the addition of verapamil hydrochloride to oxygenated glucose-rich cardioplegic solution would improve myocardial preservation. The Langendorff preparation of the isolated rat heart was used. Groups of normal (WKY) and hypertrophied (SHR) hearts were treated by five different cardioplegic methods and subjected to 90 or 30 minutes of ischemia at 28 degrees to 29 degrees C and reperfusion at 37 degrees C. The following cardioplegic solutions were used: Group A, cold (16 degrees C) Krebs-Henseleit (KH) glucose free only; Group B, KH with KCL (30 mEq/L) (16 degrees C); Group C, same as B with verapamil (10 microM); Group D, perfusion with oxygenated KH solution containing KCL (30 mEq/L) for 15 minutes prior to ischemia; and Group E, same as D with verapamil (10 microM). Recovery of contraction amplitude, ischemic contracture, coronary perfusate volume, the amount of creatine kinase in the coronary perfusate, heart rate, time of revival, O2 consumption, and ischemic contracture were measured. After 30 minutes of ischemia, we did not find any significant difference among the combinations tested with respect to contraction amplitude recovery. The hearts recovered fully. After 90 minutes of ischemia, we found that the best-protected groups in the normal hearts were Groups D and E. In the hypertrophied hearts, the addition of verapamil to the enhancement solution was harmful. The use of enhancement solution without verapamil prior to ischemia provided the best myocardial protection in the hypertrophied hearts.

Animals↗