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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 163 records · Page 9Linked to original sources

Exposure to conspecific alarm chemosignals alters immune responses in BALB/c mice.

Male BALB/cJ mice were exposed for 24 h to odors from donor mice that were either footshocked or undisturbed. Mice exposed to odors from footshocked donors had suppressed splenic IL-2 production following in vitro concanavalin A (Con A) stimulation compared to home cage or apparatus controls. Stress odor exposure also resulted in reduced natural killer (NK) cell cytotoxicity against YAC-1 tumor target cells compared to controls. Stress odor exposure 24 h after intraperitoneal injection of keyhole limpet hemocyanin (KLH) increased IgM and IgG antibody titers relative to the response of home cage or apparatus control animals. These results demonstrate that exposure to olfactory cues from stressed rodents alters both cellular and humoral immune responses. This paradigm may provide an ethnologically appropriate model of psychosocial stress in rodents.

Animals↗

Conditioned enhancement of antibody production using antigen as the unconditioned stimulus.

Antigen is the most salient stimulus for an unconditional activation of the immune system. BALB/c mice were given repeated immunizations with keyhole limpet hemocyanin (KLH) paired with a gustatory conditioned stimulus (CS). A classically conditioned enhancement of anti-KLH antibody titers was observed when conditioned mice were reexposed to the CS in the context of reexposure to a minimally immunogenic dose of that same antigen. An interaction between signals derived from the neuroendocrine and immune systems is hypothesized to mediate this conditioned immune response.

Animals↗

Renal uric acid handling in non-insulin-dependent diabetic patients with elevated glomerular filtration rates.

1. Hypouricaemia is prevalent in diabetic patients. In most of the studies, the diabetic patients had some degree of diabetic nephropathy as evidenced by a decreased glomerular filtration rate and proteinuria. Therefore we studied renal uric acid handling in a group of type II diabetic patients with elevated glomerular filtration rates. 2. Eighteen type II diabetic patients with normal kidney functions and elevated glomerular filtration rate and a group of 18 healthy, age- and weight-matched control subjects, were studied. Serum fructosamine, creatinine and uric acid levels were determined. Twenty-four hour urine collections were obtained, and microalbumin, glucose, creatinine and uric acid, were measured. 3. The creatinine clearance was higher and the serum uric acid concentration was lower in the diabetic patients (P < 0.05). The 24 h urinary uric acid excretion and filtered uric acid load were similar in both groups. However, the derived parameters of uric acid clearance and fractional excretion were significantly higher in the diabetic patients (P < 0.002 and P < 0.05, respectively). A negative correlation was apparent between serum fructosamine concentration and serum uric acid concentration (r = -0.76). A positive correlation was found between serum fructosamine concentration and fractional uric acid excretion (r = 0.64) and between serum fructosamine concentration and filtered uric acid load (r = 0.66). A positive correlation was found between creatinine clearance and 24 h uric acid excretion (r = 0.61) and between creatinine clearance and filtered uric acid load (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗

Hypertension and a tumor of the glomus jugulare region. Evidence for epinephrine biosynthesis.

Glomus jugulare tumors have been reported to secrete norepinephrine and cause severe hypertension with features similar to pheochromocytoma. In contrast, epinephrine secretion has not been observed in these neoplasms. This has been attributed to the absence of the norepinephrine-methylating enzyme, phenylethanolamine-N-methyltransferase (PNMT), required for epinephrine synthesis. We report a patient with severe hypertension caused by a glomus tumor that secreted norepinephrine and epinephrine. Following selective venous sampling, catecholamines were quantified by radioenzymatic assay. Marked elevations in norepinephrine and epinephrine release were localized to the glomus tumor. The enzymes involved in catecholamine biosynthesis, including PNMT and tyrosine hydroxylase, were identified immunocytochemically in the tumor. The glomus tumor had staining patterns identical to those observed within normal rat glomus cell. Hypertension resolved with resection of the functioning tumor. This is the first report of PNMT in a functioning paraganglioma of the glomus jugulare region. The factors that determine why functional activity is expressed only rarely by paraganglioma remain undefined.

Adult↗

Hereditary angioneurotic edema with severe hypovolemic shock.

Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients.

Abdomen, Acute↗

Summary report from the first international workshop on soluble HLA antigens. Paris, August 1992.

The First International Workshop on Soluble HLA antigens focused on the comparison of immunoassay procedures for quantitation of soluble HLA (sHLA) class I antigens and the selection of a sHLA class I antigen international standard. Several sets of serum, plasma, and cell culture supernatant specimens were assayed blindly for levels of sHLA class I antigens by 15 participating laboratories using different immunoassay formats. The sandwich ELISA using (i) for antigen capture: an anti-HLA class I heavy chain monoclonal antibody (mAb) specific for a monomorphic epitope, and (ii) for antigen detection: an anti-beta 2 microglobulin antibody-enzyme conjugate, was the assay format of choice. There was a high inter-laboratory correlation among the majority of laboratories. All serum and plasma specimens from normal donors, and from a single transplant patient, had detectable levels of sHLA class I antigens. Paired serum and plasma specimens had similar levels of sHLA class I antigens, although plasma sHLA antigens seemed more stable than serum sHLA antigens. sHLA-A2 and sHLA-B7 antigens were detected in all specimens from HLA-A2 and HLA-B7 donors, respectively, using allele-specific ELISAs. No difference in reactivity was observed for quantitation of native sHLA class I antigens whether the capture mAb was TP25.99 (alpha 3 domain-specific) or W6/32 (alpha 2 + alpha 3-specific). However, a human-mouse chimeric sHLA class I antigen reacted weakly in assays which used TP25.99 mAb. The wide variation among laboratories in their reporting of micrograms/ml units pointed to the need for an inter-laboratory standardization based on a calibrated sHLA antigen preparation. T.sB7, an sHLA-B7 antigen derived from a cell line transfected within human beta 2 microglobulin and HLA-B7 genes, was accepted as the First sHLA class I Antigen International Standard at the workshop meeting.

Alleles↗

Dissociation of blood pressure and albuminuria in normal subjects infused with angiotensin II and noradrenaline.

1. Albuminuria is a predictor of diabetic renal disease and atherosclerosis. Changes in blood pressure (BP) may influence albuminuria. 2. The effect of acute BP elevation on albumin excretion rates (AER) using noradrenaline (NA) and angiotensin II (AII) infusions in six normal subjects was examined. 3. The average rise in BP during a 120 min infusion was 23 mmHg for AII and 16 mmHg for NA. 4. There was a marked dissociation between AER and BP levels in both AII and NA infusions. 5. Previously described correlations between BP and AER in ambulatory BP studies may be explained by other factors such as exercise and postural changes.

Adolescent↗

Psychoneuroimmunology: conditioning and stress.

The acquisition and extinction of the conditioned suppression or enhancement of one or another parameter of antigen-specific and nonspecific defense system responses have been documented in different species under a variety of experimental conditions. Similarly, stressful stimulation influences antigen-specific as well as nonspecific reactions. Moreover, both conditioning and stressful stimulation exert biologically meaningful effects in the sense that they can alter the development and/or progression of what are presumed to be immunologically mediated pathophysiologic processes. These are highly reproducible phenomena that illustrate a functional relationship between the brain and the immune system. However, the extent to which one can generalize from one stressor to another or from one parameter of immunologic reactivity to another is limited. Few generalizations are possible because the direction and/or magnitude of the effects of conditioning and "stress" in modulating immune responses clearly depend on the quality and quantity of the behavioral interventions, the quality and quantity of antigenic stimulation, the temporal relationship between behavioral and antigenic stimulation, the nature of the immune response and the immune compartment in which it is measured, the time of sampling, a variety of host factors (e.g. species, strain, age, sex), and interactions among these several variables. It seems reasonable to assume that the immunologic effects of behaviorally induced neural and endocrine responses depend on (interact with) the concurrent immunologic events upon which they are superimposed. Conversely, the efficacy of immunologic defense mechanisms seems to depend on the neuroendocrine environment on which they are superimposed. We seek to determine when and what immunologic (or neuroendocrine) responses could be affected by what neuroendocrine (or immunologic) circumstances. We therefore need studies that provide a parametric analysis of the stimulus conditions, the neuroendocrine and/or immunologic state upon which they are superimposed, and the responses that are being sampled. The neural or neuroendocrine pathways involved in the behavioral alteration of immune responses are not yet known. Both conditioning and stressor-induced effects have been hypothesized to result from the action of adrenocortical steroids, opioids, and catecholamines, among others. Indeed, all of these have been implicated in the mediation of some immunologic effects observed under some experimental conditions. We assume that different conditioning and stressful environmental circumstances induce different constellations of neuroendocrine responses that constitute the milieu within which ongoing immunologic reactions and the response to immunologic signals occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Conditioning, Psychological↗

Transforming growth factor beta (TGF beta) is produced by and influences the proliferative response of Xenopus laevis lymphocytes.

Both TGF beta 2 and 5 have been described in the South African clawed frog Xenopus laevis and have been cloned from the tadpole-derived fibroblast cell line, XTC. Because TGF beta has such a profound inhibitory effect on the mammalian immune system, this study was performed to determine whether TGF beta: (a) has any in vitro effects on the growth of Xenopus lymphoblasts, and (b) is produced by mitogen-activated Xenopus lymphocytes. Following stimulation with mitogen or alloantigen, T lymphocytes from Xenopus secrete a T-cell growth factor (TCGF) that is functionally homologous to mammalian interleukin-2 (IL-2). Both recombinant human TGF beta 1 and Xenopus TGF beta 5 inhibit TCGF-induced proliferation of Xenopus splenic blasts and this inhibition can be reversed with anti-pan TGF beta antiserum. The Xenopus mitogen-induced saturated ammonium sulfate precipitated TCGF-containing supernatant (SAS TCGF SN) also contains latent TGF beta as assayed on mink lung fibroblasts and Xenopus splenic blasts, and experiments utilizing anti-TGF beta antiserum showed that only TGF beta 5 is present in this supernatant.

Animals↗

Further characterization of an interleukin-2-like cytokine produced by Xenopus laevis T lymphocytes.

A T-cell growth factor (TCGF) is produced by antigen- or mitogen-stimulated T lymphocytes from the South African clawed frog Xenopus laevis. This study further defines the physical and biological properties of this cytokine and demonstrates that TCGF is biochemically similar to mammalian interleukin-2 (IL-2). Biologically active TCGF eluted from SDS-PAGE displays a M(r) of 16 kD and lectin-affinity chromatography indicates that the three-dimensional configuration of carbohydrates on TCGF and human IL-2 is similar. Secretion of TCGF is detectable 1 day after stimulation of splenocytes with the T-cell mitogen phytohemagglutinin (PHA) and peaks following 2 to 3 days of stimulation. Finally, despite the biological and physical similarities between Xenopus TCGF and mammalian IL-2, anti-human IL-2 monoclonal antibodies do not recognize Xenopus TCGF.

Animals↗

Effect of dietary manipulations on glomerular filtration rate of mice offspring of nephrectomized mothers.

We have previously reported that mice, offspring to uninephrectomized mothers, have greater than normal kidneys with supernumerary glomeruli. In this study we assessed glomerular filtration rate (GFR) in 40 mice offspring of nephrectomized mothers and 40 mice offspring of sham-nephrectomized animals aged 7 weeks. Each group was divided into 4 equal subgroups according to the following dietary manipulations: regular, high protein, high salt and high protein/high salt. At the end of 1 week, GFR was determined by 51Cr EDTA. In the first group, GFR was significantly greater in each experimental subgroup compared to control. In the offspring of sham-nephrectomized mothers, only the subgroup on the combined diet had a significantly greater GFR. We conclude that the capacity to raise GFR in response to dietary manipulations is greater in offspring of nephrectomized mothers. It remains to be elucidated whether the difference results from the increased number of nephrons or from an augmented single nephron GFR reserve.

Animals↗

The Drosophila Ras2 and Rop gene pair: a dual homology with a yeast Ras-like gene and a suppressor of its loss-of-function phenotype.

The promoter of the Drosophila melanogaster Ras2 gene is bidirectional, regulating an additional gene oriented in the opposite polarity. The two divergently transcribed genes are only 93 bases apart and deletion analysis proved that common cis-acting elements within this promoter region are required for the transcriptional activity of both genes. We cloned the gene paired with Ras2 in the bidirectional promoter and isolated cDNAs corresponding to its mRNA. The Ras opposite (Rop) gene encodes for a 68 x 10(3) M(r) protein which shares sequence homology with the members of a novel Saccharomyces cerevisiae gene family, including the SLY1, SEC1 and VPS33 (SLP1) genes, all of which are involved in vesicle trafficking among yeast cellular compartments. A highly conserved motif in this family is also found in beta-COP, a coat protein isolated from rat Golgi-bound nonclathrin vesicles. Thus, the Rop protein may be a component of one of the vesicle trafficking pathways in Drosophila cells. The Rop gene expression during embryogenesis is restricted to the central nervous system (CNS) and the garland cells, a small group of nephrocytes that takes up waste materials from the haemolymph by endocytosis. Ras2 is also expressed in the embryonic garland cells. In postembryonic stages, the two genes are co-expressed in the larval salivary glands and the central nervous system, and in the adult CNS and reproductive systems. Interestingly, the S. cerevisiae SLY1-20 allele is a suppressor of the loss of the YPT1 gene, a ras-like gene implicated in vesicle translocation, suggesting that the two genes may interact with one another. Since Sec1p and beta-COP may also interact with small GTP-binding proteins of the ras superfamily, it is conceivable that the Rop and Ras2 gene products are not just co-expressed in common tissues, but may also functionally interact with one another in these tissues.

Amino Acid Sequence↗

Equine cricoid cartilage densitometry.

The density of the cricoid cartilage from 29 equine larynges collected from an abattoir was determined by dual photon absorptiometry (DPA). Densities of the right and left cricoid cartilages were highly correlated. No correlation was found between age of the horse and the density of the cricoid cartilage.

Absorptiometry, Photon↗

Renal mononuclear cells secrete a factor triggering mesangial cell proliferation.

Thirty-six Charles River rats underwent left unilateral nephrectomy and 18 counterparts had sham nephrectomy. After 48 h the kidneys of all animals were removed, and renal mononuclear cells (RMNC) harvested. The RMNC were cultured in RPMI 1640 medium supplemented with either 20% fetal calf serum or sera procured from sham operated rats, or from nephrectomized animals. Ten days later the conditioned media of RMNC cultures were collected. Peripheral blood mononuclear cells (PBMC) from sham-operated or nephrectomized rats were also grown in RPMI 1640 supplemented with 20% fetal calf serum, sham serum or post-nephrectomy serum. The conditioned media of PBMC cultures were also collected after 10 days. Mesangial cells procured from kidneys of different normal animals were cultured in DMEM/F12HAM cell culture medium supplemented with 50% of the various RMNC- or PBMC-conditioned media. Proliferation of mesangial cells grown in conditioned medium of post-nephrectomy RMNC which had been precultured with post-nephrectomy serum was significantly augmented compared with control or any other experimental situation. There was no statistically-significant difference between proliferation rates of mesangial cells cultured in any other medium of control or experimental RMNC or PBMC. We conclude that following unilateral nephrectomy, RMNC of the remaining kidney are activated to secrete, under a sustained signal of post-nephrectomy serum, a growth factor(s) stimulating proliferation of normal mesangial cells.

Animals↗

Expression of the leukemia-associated gene, p18, in normal and malignant tissues; inactivation of expression in a patient with cleaved B cell lymphoma/leukemia.

p18 is a well conserved gene coding for an 18 kDa cytosolic phosphoprotein. Although the function of p18 is unknown, it is suspected of playing a role in regulation of cell proliferation or the proliferation-differentiation switch. Here we have found p18 mRNA expression highest in testis, brain, thymus and a multipotent hematopoietic stem cell line and lowest in liver. p18 was also expressed vigorously in all but one of 85 diverse tumor cell lines and primary human malignant specimens examined. In five primary tumors, expression was substantially elevated with respect to expression in contiguous normal tissue. Expression in chronic phase chronic myelogenous leukemia cells was far greater than in normal blood cells and increased with progression of disease. In liver material, the highest level of p18 was found in a primary hepatoblastoma, a stem cell tumor, whereas a benign adenoma demonstrated very low level expression. Cells from a cleaved B cell lymphoma/leukemia failed to express p18 whereas 18 specimens from other B lymphoid malignancies, including a second cleaved cell malignancy, expressed p18 at substantial levels. These data are consistent with p18 playing a role in control of cell proliferation in at least certain tissues. The questions arise if high level p18 expression in certain malignancies may play a primary role in driving cell proliferation or, based on chromosomal localization and inactivation of p18 expression in one lymphoma, if p18 may act as a tumor suppressor.

Carcinoma, Hepatocellular↗

[Cimetidine hepatitis].

A 41-year-old man with rheumatoid arthritis developed severe acute hepatitis 3 days after starting cimetidine for duodenal ulcer. Other causes were ruled out and he recovered after cimetidine was discontinued. Mild transient elevations of hepatic enzymes have been reported in 3.6% of patients taking cimetidine. However, only 12 cases of severe acute hepatitis associated with cimetidine, mostly secondary to idiosyncrasy, have been reported in the English literature. This rare but serious complication of cimetidine should be kept in mind.

Acute Disease↗