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Biomedical subjects

S Grossman

Publications and source records attributed to S Grossman.

At least 19 recordsLinked to original sources
PubMed1995

Lipoxygenase activity in rat dermis and epidermis: partial purification and characterization.

Lipoxygenase (LOX) activity in epidermis and dermis was distributed among microsomal and cytosolic fractions. The main products of polyunsaturated fatty acid metabolism were 12-hydroperoxy-cis-5,8,14, trans-10-eicosatetraenoic acid (12-HPETE), 15-hydroperoxy-cis-5,8,11, trans-13-eicosatetraenoic acid (15-HPETE) and 13-hydroxy-cis-9, trans-11-octadecadienoic acid (13-HOD). Enzyme activities were isolated from rat dermis and epidermis by ammonium sulphate precipitation, hydrophobic chromatography and gel filtration. In the dermis, activity was found at a molecular mass of 68 kDa, a pI of 4.6 and a Km of 50 microM. This activity was inhibited by known LOX inhibitors. The main reaction products indicated that this was 15-LOX. In the epidermis, activity was found in a fraction with a molecular mass of 68 kDa, a pI of 4.6 and a Km of 80 microM. Activity was inhibited by known LOX inhibitors whereas the reaction products indicated that this was 12-LOX. LOX activity in rat skin may involve one enzyme with dual regional specificities or may comprise two different enzymes.

Animals↗
PubMed1995

Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa.

The Epstein-Barr virus (EBV) nuclear protein 3C (EBNA 3C) is essential for EBV-mediated transformation of primary B lymphocytes, is turned on by EBNA 2, and regulates transcription of some of the viral and cellular genes which are regulated by EBNA 2. EBNA 2 is targeted to response elements by binding to the DNA sequence-specific, transcriptional repressor protein J kappa. We now show that EBNA 3C also binds to J kappa. EBNA 3C causes J kappa to not bind DNA or EBNA 2. J kappa DNA binding activity in EBV-transformed lymphoblastoid cells is consequently reduced. More than 10% of the EBNA 3C coimmunoprecipitated with J kappa from extracts of non-EBV-infected B lymphoblasts that had been stably converted to EBNA 3C expression. EBNA 3C in nuclear extracts from these cells (or in vitro-translated EBNA 3C) prevented J kappa from interacting with a high-affinity DNA binding site. Under conditions of transient overexpression in B lymphoblasts, EBNA 2 and EBNA 3C associated with J kappa and less EBNA 2 associated with J kappa when EBNA 3C was coexpressed in the same cell. EBNA 3C had no effect on the activity of a -512/+40 LMP1 promoter-CAT reporter construct that has two upstream J kappa sites, but it did inhibit EBNA 2 transactivation of this promoter. These data are compatible with a role for EBNA 3C as a "feedback" down modulator of EBNA 2-mediated transactivation. EBNA 3C could, in theory, also activate transcription by inhibiting the interaction of the J kappa repressor with its cognate DNA. The interaction of two viral transcriptional regulators with the same cell protein may reflect an unusually high level of complexity or stringency in target gene regulation.

Antigens, Viral↗
PubMed1995

Unit-based nursing research.

Sixteen nurses working in a variety of clinical settings met to learn about unit based nursing research. Each had a different perception of the concept but all agreed it was time to validate, via research, what nurses were actually doing to impact patient outcomes. The individual members achieved their goals of learning the steps in the research process and planning a study for their own unit. The mentoring received from the researcher was viewed as a necessary component of accomplishing their projects.

Clinical Nursing Research↗
PubMed1995

Dapsone-induced hemolytic anemia: role of glucose-6-phosphate dehydrogenase in the hemolytic response of rat erythrocytes to N-hydroxydapsone.

Individuals deficient in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) show about a 2-fold increase in sensitivity toward dapsone-induced hemolytic anemia. Rat studies have shown that the hemolytic activity of dapsone resides in its N-hydroxy metabolites; exposure of rat red cells to N-hydroxy-dapsone in vitro followed by readministration to isologous rats results in premature splenic sequestration of the damaged cells. This study examines the ability of the steroid, epiandrosterone, to inhibit rat red cell G6PD and the effect of such inhibition on the susceptibility of rat red cells to N-hydroxydapsone hemolytic activity. Epiandrosterone was found to inhibit rat red cell G6PD uncompetitively and to suppress red cell hexose monophosphate shunt activity by more than 95%. Epiandrosterone suppression of rat red cell G6PD activity resulted in about a 2-fold increase in sensitivity of the rat cells to N-hydroxydapsone hemolytic activity, and a modest but significant increase in depletion of red cell glutathione. In contrast, suppression of rat red cell catalase activity by aminotriazole had no effect on the hemotoxicity of N-hydroxydapsone. Epiandrosterone appears to be a useful tool to explore the mechanism by which G6PD deficiency enhances susceptibility to hemolytic drugs.

Amitrole↗
PubMed1994

Genetic and biochemical evidence that EBNA 2 interaction with a 63-kDa cellular GTG-binding protein is essential for B lymphocyte growth transformation by EBV.

Epstein-Barr virus (EBV) nuclear protein 2 (EBNA 2) is an acidic transcriptional transactivator of virus and cell gene expression and is essential for growth transformation of primary B lymphocytes. EBNA 2 transactivation of response elements (E2REs) can be mediated by interaction with a GTGGGAA-specific DNA-binding factor(s). We now purify the factor by S-Sepharose and EBNA 2 affinity chromatography and identify it as a single 63-kDa protein. The protein is shown to specifically coimmunoprecipitate with EBNA 2 from lymphoblasts transfected with an EBNA 2 FLAG expression vector. Mutation of GTG to TCT in a GTGGGAA motif common to the Cp, LMP2, and LMP1 promoters results in loss of recognition by p63. EBNA 2 amino acids 310-336 are sufficient for p63 binding. The only motif in this 27 amino acid sequence which is common to the EBNA 2 genes of EBV types 1 and 2 is GPPWWPP (I/V) (C/R) DP, which is therefore likely to mediate p63 interaction. Mutation of WW to SS or FF ablates interaction with p63, indicating that both the hydrophobic and aromatic characteristics of WW are essential for its "key" interaction with p63. EBNA 2 with a WW mutated to SS is also unable to marker rescue primary B lymphocyte transforming virus from cells infected with an EBNA 2-deleted virus, while otherwise isogenic wild-type EBNA 2 readily marker rescues transforming virus in parallel experiments. EBNA 2 transactivation through the Cp E2RE is completely abolished by the WW to SS mutation while transactivation of -234 to +40 LMP1 E2RE is only partially affected. These genetic and biochemical experiments support the hypothesis that EBNA 2 WW interaction with a p63 GTGGGAA-binding protein is essential for EBV-mediated cell growth transformation because it specifically associates EBNA 2 with its response elements. This enables the EBNA 2 acidic domain to transcriptionally transactivate specific genes.

Amino Acid Sequence↗
PubMed1993

A strategy for decreasing anxiety of ICU transfer patients and their families.

With the growing number of clients transferred out of the intensive care units (ICUs) following increasingly shorter stays, time constraints have become a barrier to effective teaching. Written information that is readily available to clients helps resolve this problem. A pamphlet (in Spanish and English) was developed to ease the move for patients, families, and critical care and medical nurses from a medical ICU (MICU) to a general floor.

Anxiety↗
PubMed1992

Developmental changes in hepatic basolateral membrane lipid composition and fluidity.

Membrane fluidity and lipid composition influence the activity of a variety of membrane proteins. Decreased rates of hepatic ion clearance are associated with the neonatal period. We postulated that hepatic basolateral membranes derived from suckling animals might be less fluid than those from adult animals. Basolateral membrane vesicles were prepared from the livers of 1-week-old (SBLMV) and adult (ABLMV) rats by a Percoll gradient method. Na+/K(+)-ATPase activities were similar in the two groups. Double bond index, cholesterol and cholesterol/phosphorus ratios were significantly higher in SBLMV compared with ABLMV, while lipid phosphorus and relative percentages of phospholipid subclasses did not differ. Fluorescence anisotropy measured using diphenylhexatriene as well as 2-(9-anthroyloxy)stearate was significantly greater in SBLMV compared with ABLMV, while measurements made with 12-(9-anthroyloxy)stearate were similar in both age groups. Mean excited state lifetimes, lifetime distributions, and rotational correlation times were similar in both groups. These data suggest that hepatic basolateral membranes derived from suckling rats are less fluid than those from adult animals and further suggest that this difference may be due to increased cholesterol in hepatic basolateral membranes derived from suckling animals.

Animals↗
PubMed1992

Lipoxygenase activity in the brain regions of young chicks: isolation and some properties.

1. The lipoxygenase (LOX) oxygenation pathway of arachidonic acid was investigated in the cerebellum and cerebral hemispheres of young chicks. 2. Lipoxygenase products consisted mainly of 15-hydroxyeicosatetraenoic acid (15-HETE), accompanied by the 15-hydroperoxy analog (15-HPETE) and the 5-HETE product. 3. The yield of 15-HETE was 3 times greater in the cerebellar system than in the cerebrum. 4. PLA2 activity of the cerebellum was twice that of the cerebrum. 5. Affinity chromatography revealed 2 brain fractions with LOX activity which were assayed with either linoleic or arachidonic acid as substrate. 6. The fraction eluted with 0.2 M sodium acetate pH 5.0, produced a higher yield and enrichment of LOX activity than the eluate obtained with 0.1 M Tris-HCl buffer (pH 8.0). 7. A considerably higher yield and enrichment of the enzyme was achieved when the starting material was the cerebellum, compared to the cerebrum. 8. The optimal pH for both purified fractions from cerebrum and cerebellum was 6.5, with either linoleic or arachidonic acid as substrate. 9. The cerebral LOX yielded Michaelis-Menten kinetics when linoleic acid was the substrate, while the corresponding plots for the cerebellar enzyme were sigmoidal. 10. Arachidonic acid as substrate produced sigmoidal plots, except at pH 5.0, where Michaelis-Menten kinetics were observed. 11. These results and the elevated activities of PLA2 and 15-LOX could be significant in relation to the special vulnerability of the cerebellum in chick nutritional encephalomalacia.

Animals↗
PubMed1992

Minimizing diagnostic blood loss in critically ill patients.

BACKGROUND: Blood loss from diagnostic procedures in critically ill patients needs to be minimized. Traditionally, when drawing blood from arterial lines, the initial sample used to clear the line has been discarded (open method). Use of a temporary reservoir enables this discard sample to be returned to the patient (closed method). METHODS: Critically ill surgical patients were prospectively randomized to the open or closed method of drawing blood from arterial lines. Blood loss to diagnostic sampling was measured in both groups. RESULTS: A comparison study (n = 1657) of these two methods revealed that blood loss to the patient was significantly decreased (P << .01) using the closed method. Mean blood loss per patient per day was 69 mL in the open group (n = 873) vs 35 mL in the closed group (n = 784). CONCLUSIONS: Use of the closed method when drawing blood from arterial lines results in a significant decrease in blood lost to diagnostic procedures.

Adult↗
PubMed1991

The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis.

The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.

Animals↗
PubMed1990

Role of lipoxygenase in the mechanism of acrosome reaction in mammalian spermatozoa.

The acrosome reaction (AR) in bull spermatozoa was induced by the Ca2(+)-ionophore A23187, by dilauroylphosphatidylcholine or by arachidonic acid in the presence of Ca2+ in the incubation medium. The occurrence of AR was determined by following the release of acrosin from the cells. Nordihydroguaiaretic acid (NDGA), an inhibitor of both lipoxygenase and prostaglandin-synthetase, caused 35%, 43% and 69% inhibition of AR at concentrations of 1, 10 or 100 microM, respectively. Eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, caused 17%, 61% and 77% inhibition of AR at concentrations of 20, 40 or 80 micrograms/ml, respectively. When AR was induced by arachidonic acid, ETYA, causes 36% and 58% inhibition at concentrations of 2 or 20 micrograms/ml, respectively. Under identical conditions, 100 microM indomethacin, a specific inhibitor of prostaglandin-synthetase, showed no inhibition but rather 35% stimulation at acrosin release rate. The fact that AR is inhibited by NDGA and not by indomethacin indicates that the lipoxygenase, rather than prostaglandin-synthetase, is involved in the mechanism of AR. Since the inhibition by NDGA is seen in the presence of the Ca-ionophore, we suggest that lipoxygenase activity is not involved in enhancing calcium transport into the cell, but rather at other steps in AR mechanism. A thin-layer chromatography revealed the presence of 15-HETE, the classical product of 15-lipoxygenase activity, which was identified by HPLC. Under AR conditions, there is an elevation of lipoxygenase products and the addition of NDGA caused a reduction in their levels. The inhibition of acrosin release by NDGA can be eliminated by adding 15-HETE or 15-HPETE to the incubation medium. In conclusion, we suggest here for the first time, a physiological role for 15-lipoxygenase in the mechanism of AR in mammalian spermatozoa.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Metabolic heterogeneity in RIF-1 tumours detected in vivo by 31P NMR spectroscopy.

The spatial distribution of phosphate metabolites and pH within subcutaneously implanted RIF-1 tumours was determined by 1-dimensional phosphorus chemical shift imaging. 31P spectra from two to three 4 mm thick cross-sectional slices were obtained for each tumour. Quantitative morphometry was used to estimate the amount of necrosis within those slices. A spatially heterogeneous distribution of phosphate metabolites and pH was detected in most of the tumours. Levels of necrosis ranged from 0-24% for the tumours in this study. There was no significant correlation between the extent of necrosis over this range and levels of metabolites or pH, suggesting that factors besides necrosis can contribute to spectral heterogeneity.

Animals↗
PubMed1990

Spontaneous release of a factor with interleukin-3-like activity by human lymphocytes and monocytes.

The production of a factor with interleukin-3-like activity (IL-3-LA) by cultured human peripheral-blood mononuclear cells has been studied. Culture supernatants spontaneously derived from lymphocytes or monocytes stimulated the proliferative activity of 3 IL-3-dependent cell lines. Purification of this factor by gel filtration-high-pressure liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated the presence of a glycoprotein with a molecular weight of 25-30 kilodaltons and an isoelectric point of 7.6. The biochemical characteristics of the IL-3-LA derived from human monocytes and lymphocytes were very similar. The biological activity of the semipurified factor was tested on mononuclear cells from fetal cord blood. It was found that after 21 days 40% of the cells in the culture were mature basophils which released 15-18 ng histamine/10(6) cells.

Basophils↗
PubMed1989

Colonoscopic screening of persons with suspected risk factors for colon cancer: II. Past history of colorectal neoplasms.

Colonoscopic screening has been recommended for all persons who have had a colorectal adenoma or carcinoma. Such persons have been assumed to be at increased risk of having additional, asymptomatic colorectal neoplasms, the removal of which would reduce morbidity and mortality from colorectal cancer. In this prospective study, initial colonoscopy was performed on 544 asymptomatic subjects with past histories of colorectal index lesions ranging from small tubular adenomas to invasive cancers. In 402 subjects whose worst index lesion was an adenoma, the prevalence of neoplasms detected at colonoscopy, above the reach of the rigid sigmoidoscope, increased with age, male sex, black race, and the number and size of their index adenomas. In 142 subjects whose worst index lesion was invasive cancer, colonoscopy findings were marginally related to age and white race. A subgroup of 133 subjects whose worst index lesion was a single, small (less than 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer had only a 3% prevalence of advanced colonic neoplasms (tubular adenomas greater than or equal to 10 mm in diameter; tubulovillous, villous, or severely dysplastic adenomas; or invasive cancers) found on colonoscopy--no greater than would be expected in the general population. Subgroups of the remaining 411 subjects, who had advanced or multiple index lesions, had prevalences of advanced neoplasms ranging from 8% to 18%. These findings indicate that for persons whose only risk factor is a single small tubular adenoma, current screening guidelines could be modified to recommend techniques less costly and less invasive than colonoscopy.

Adenoma↗
PubMed1989

Arachidonic acid metabolism by perfused ram testis.

1. Arachidonic acid was metabolized by lipoxygenase and prostaglandin synthetase enzymes systems in the perfused ram testis. 2. The major product of the prostaglandin synthetase was 6-keto-PGF1 alpha (6KF). 3. Addition of testosterone resulted in a significant increase in the 6KF. 4. Arachidonic acid (AA) as well as testosterone penetrated the perfused testis. 5. Both 15-HPETE and 15-HETE, the products of the 15-lipoxygenase enzyme, were detected. 6. Addition of 0.1% BSA changed the pattern of the oxidized arachidonic acid metabolism.

Animals↗