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Biomedical subjects

S Hirsch

Publications and source records attributed to S Hirsch.

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

Isolation and sequence of a cDNA clone encoding the 31-kDa subunit of bovine kidney vacuolar H+-ATPase.

We have isolated a cDNA encoding the 31-kDa subunit of the bovine kidney vacuolar H+-ATPase. The composite sequence contains 1219 base pairs, which includes the entire 678-base-pair coding region. A lysine-rich sequence previously found in the Na+, K+-ATPase alpha subunit and the H+,K+-ATPase was identified in the 31-kDa subunit. An RNA blot and an immunoblot demonstrated variable 31-kDa subunit expression and immunoreactivity in different tissues; the highest levels were observed in kidney medulla and brain with both types of analysis. The isolation of a cDNA for the 31-kDa subunit is an important step in understanding this subunit's role in the function and regulation of the vacuolar H+-ATPase.

Amino Acid Sequence↗
PubMed1988

Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics.

This study analyzes whether increased body weight is related to histological liver damage in chronic alcoholic patients. Data from 152 recently abstinent alcoholics without evidences of liver failure were analyzed. Liver biopsies were scored for the presence of fat, necrosis, fibrosis, inflammation, and Mallory material. Total histological score correlated significantly with body weight (BW), length of alcoholism (L), and age (A) but not with the amount of ethanol ingested (E). Forward stepwise multiple regression analysis with histological score as the dependent variable gave significant F values for BW and L but not for A. Patients with severe damage had higher BW than patients with mild damage. The group with BW greater than 110% showed a higher histological score. These results confirm the association between increased BW and liver damage in asymptomatic alcoholic patients suggesting that overweight is a risk factor for alcoholic liver disease.

Alcoholism↗
PubMed1988

Localization of a proton-pumping ATPase in rat kidney.

The distribution of vacuolar H+ATPase in rat kidney was examined by immunocytochemistry using affinity-purified antibodies against the 31-, 56-, and 70-kD subunits of the bovine kidney proton pump. Proximal convoluted tubules were labeled over apical plasma membrane invaginations, and in the initial part of the thin descending limb, apical and basolateral plasma membranes were moderately stained. Thick ascending limbs and distal convoluted tubules were apically stained although the intensity was greater in the distal convoluted tubule. Collecting duct principal cells were virtually unlabeled, but intercalated cells had intense staining with an apical, basolateral or diffuse pattern in the cortex, and exclusively apical staining in the medulla. These results (a) show the presence of an H+ATPase in the apical plasma membrane of the proximal tubule that may contribute to H+ transport in this segment; (b) provide direct evidence that the intercalated cell contains most of the H+ATPase detectable in the collecting duct, supporting its proposed role in H+ transport; (c) demonstrate that subpopulations of cortical intercalated cells have opposite polarities of an H+ATPase, consistent with the presence of both proton- and bicarbonate-secreting cells; and (d) suggest a role for the H+ATPase in acid/base regulation or H+ transport in segments other than the collecting duct and the proximal tubule.

Animals↗
PubMed1987

Inhibitory action of spermidine on formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate production in human neutrophils.

The effect of the polyamine, spermidine, on formyl-methionyl-leucyl-phenylalanine stimulated hydrolysis of polyphosphoinositides was examined in purified human neutrophils by measurement of inositol phosphate production from radioactively labelled inositol. Spermidine inhibited formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate production by neutrophil in a dose dependent manner. Inhibition of formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate accumulation by spermidine was maximal at 10 microM and the IC50 value for this effect was 4.2 microM spermidine. This action of spermidine, thought to be mediated by a membrane component other than phospholipase C, may reflect a control mechanism modulating the response of the polyphosphoinositide system.

Adult↗
PubMed1987

A simple technique to accurately determine intra-abdominal pressure.

The determination of intra-abdominal pressure (IAP) may be useful in a variety of clinical situations. Despite this, invasive IAP monitoring is seldom performed due to the risks involved. Using a standard canine model of increased IAP, we evaluated the accuracy of transurethral bladder catheter pressure in reflecting IAP. Throughout the range of IAP studied (10 +/- 5 to 70 +/- 10 mm Hg), bladder pressure did not differ significantly from the direct measurement of IAP. We conclude that the measurement of bladder pressure using a standard transurethral bladder catheter provides an accurate determination of IAP.

Abdomen↗
PubMed1987

The threshold-of-interference test: a new test of interhemispheric suppression in brain injury.

A new procedural version of the Willeford competing sentences test (Willeford. Audiol Hear Educ 1976;2:12-20) is introduced here for use with brain damaged patients. The threshold-of-interference test seeks the minimal level of the competing sentences at which the patient can no longer repeat the message at the test ear. Findings are reported for normal controls and for brain damaged adults, with clinical data and computerized axial tomography scan evidence. The threshold-of-interference test appears to be efficient, quick in administration, and particularly useful in exposing auditory processing anomalies, especially in right hemisphere damage.

Aged↗
PubMed1987

Use of the isolated perfused kidney model to assess the acute pharmacologic effects of cyclosporine and its vehicle, cremophor EL.

"Nephrotoxicity" secondary to cyclosporine and its clinically used vehicle, Cremophor EL, was examined in the isolated perfused rat kidney model. This model allows the serial determination of renal hemodynamic and tubular functional studies over a 3-hr duration using a normothermic, low hematocrit (13-15%) perfusion system. Initial studies indicated that the addition of small quantities of Cremophor EL resulted in marked renal vasoconstriction with decreased renal blood flow and deterioration in renal tubular function. These effects were highly significant and were of the same magnitude whether or not cyclosporine was present in the system. Cyclosporine was therefore examined after being dissolved in another vehicle, methanol. A 10% (v/v) amount of plasma was necessary in the perfusate to prevent significant adsorption of cyclosporine to the perfusion apparatus. Cyclosporine at concentrations below 100 ng/ml resulted in minor changes in renal hemodynamics. Beginning at 100 ng/ml glomerular filtration rate dropped significantly and renal vascular resistance increased three-fold. Fractional excretion of sodium significantly increased and the urine:plasma inulin ratio significantly decreased. We conclude that the clinically used drug vehicle, Cremophor EL, has significantly adverse effects on renal hemodynamics and tubular function. In addition, CsA causes similar renal toxicity in a dose-dependent fashion. Simultaneous administration of these two nephrotoxic agents could contribute to the high incidence of acute renal failure seen after transplantation. These observations suggest that an alternate vehicle with less renal toxicity might significantly decrease the incidence of this clinical problem.

Animals↗
PubMed1987

Interhemispheric suppression: a test of central auditory function.

Two groups of brain damaged adults, those with cerebrocranial injury (CCI) and victims of cerebrovascular accident (CVA) were tested with the competing sentences test of Willeford (In: Central Auditory Dysfunction. New York: Grune and Stratton, 1977: Chap 2). The main purpose was the exposure of functional disorders of communication in such patients who test within normal or near-normal limits on routine audiological testing and also on tests for aphasia. Of 142 serially admitted CCI patients, 43%, many with diffuse lesions, gave abnormal responses, mostly at the left ear, with 19 of them showing total extinction at that ear. On two sound field competing message tests the CCI patients were significantly poorer than normal controls. CVA patients with confirmed right hemisphere lesions tended strongly toward left ear suppression, while left hemisphere damaged patients often showed bilateral drop in scores. It is clear that brain damaged patients can have central dysfunction of auditory processing despite normal findings on routine audiological tests and tests for aphasia. The implications for activities of daily living and for habilitation are discussed.

Adult↗
PubMed1986

A second open letter to the General Medical Council.

In an open letter to the General Medical Council this independent group, drawn from several branches of the profession, expressed the belief that undergraduate medical education was failing in two respects; first, in the extent to which it equips doctors with the capacity to think critically for themselves; and secondly, in the degree to which it inculcates a broad and sensitive outlook towards the health of both individuals and communities. A remedy for both lies, in our opinion, in the better co-ordination of the different stages of medical education. Particularly important in this context is the period immediately after graduation. We therefore welcome the attention which the General Medical Council's Education Committee is now paying to this second stage. We welcome also the view which it has expressed that it is necessary to continue a broad education into the period when the qualified doctor is assuming responsibility for patient care. In this second letter we propose and discuss six aims for this period; and changes in educational organization needed if these aims are to be fulfilled.

Clinical Clerkship↗
PubMed1986

Interaction of West Nile virus with primary murine macrophages: role of cell activation and receptors for antibody and complement.

We have measured growth of West Nile virus in mouse primary peritoneal macrophages (resident, thioglycolate elicited, and Mycobacterium bovis BCG activated) and in macrophagelike (P338D1) and nonmacrophage (L929, PS clone D) cell lines infected in the absence or presence of specific antibodies (immunoglobulin G ([IgG], IgM), and complement. Monoclonal antibodies directed against Fc receptors (IgG1/2b, 2.4G2) and type 3 complement receptors (Mac-1) were used to define the role of each receptor. Virus yield depended on a balance between enhancement and neutralization and was influenced by the physiologic state of the macrophage, the receptor pathway of viral entry, the mouse strain and age of donor. BCG-activated macrophages displayed a greater ability to restrict West Nile virus than nonactivated cells only in the presence of antiviral IgM, with or without complement; the Fc receptors for various classes of IgG mediated striking enhancement. These studies identify some of the complex innate and acquired factors that determine the interaction between West Nile virus and primary macrophages in vitro.

Age Factors↗
PubMed1985

Interruption of cholinergic afferent pathways to the amygdala failed to alter electrical kindling.

We investigated the hypothesis that the cholinergic system is involved in the process of amygdala kindling. Electrical kindling of the amygdala was associated with an increase in the concentration of acetylcholine in the kindled amygdala and the ipsilateral hippocampus but was not associated with any alteration of choline acetyltransferase activity. Destruction of cholinergic neurons in the lateral preoptic area significantly decreased the activity of choline acetylase in the ipsilateral amygdala, but had no effect on the duration of time to kindling. We interpret these findings as indicating that the cholinergic system is affected by the kindling process, but does not seem to be crucial to the phenomenon.

Acetylcholine↗
PubMed1985

Auditory perception in patients with CVA without aphasia.

Tests of central auditory function were performed variously on 64 patients with hemiplegia who had suffered a single stroke but with minimal or no aphasia symptoms and with essentially normal hearing. Both right and left hemisphere lesions were represented for comparison of effects on the tests. Reports of central auditory dysfunction generally assume localization in the temporal lobes. Since it was apparent that our tests were revealing positive findings in patients in whom there was no recognized evidence of temporal lobe involvement we deliberately selected for one study 34 patients without clinical signs of such lesions. The tests required selective listening in which patients had to a) perceive and repeat a prime message in the presence of a simultaneously competing meaningful message, either under earphones or in the sound field (loudspeaker), and b) repeat all words in a classic dichotic listening task. The tests reveal different dysfunctions in right vs left hemisphere damage and document that compensatory transfer of function from the usually dominant left side to the fight hemisphere usually occurs only in young children. The dysfunctions appear to be unrelated to temporal lobe lesions.

Adult↗
PubMed1985

Auditory perpetual dysfunction in patients with CCI, with implications for therapy.

Injury to the head, as from impact, can result in damaged function of the auditory receptive (peripheral) or perceptual (central) system, or both. The altered function may be clearly apparent, as in a loss of hearing, or may be exposed only through specially devised tests. At the Loewenstein Rehabilitation Hospital tests were designed or adapted to evaluate processing in the auditory periphery, the brain stem and the cortex. With speech as the the stimulus the tasks explore binaural interaction, cerebral hemisphere dominance and suppression, and cognitive efficiency in understanding degraded speech messages. Other stimuli, such as pure tones and musical patterns are employed to reveal dysfunction on various levels of the system. This report concentrates on tests which require the cerebral hemispheres to listen competitively. Results are given for earphone listening and for two new types of selective listening tasks in the sound field (loudspeaker) mode.

Adult↗