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Biomedical subjects

S Jacobs

Publications and source records attributed to S Jacobs.

At least 127 records · Page 7Linked to original sources
PubMed1991

A graded combination regimen for maintenance of gastric pH above 3.5 in critically ill patients.

Prophylaxis of acute upper gastrointestinal bleeding by control of gastric pH has been widely advocated for intensive care patients. H2-blockers and antacids have been used and demonstrated to be incompletely effective at maintaining gastric pH above 4. A study of 100 patients measured the efficacy of two-hourly gastric pH measurement and titrated therapy consisting of five levels: 1. no therapy 2. ranitidine 50 mg 8 hourly intravenously 3. ranitidine plus Mylanta 30 ml 2 hourly by nasogastric tube 4. ranitidine plus Mylanta 60 ml 2 hourly and 5. ranitidine 100 mg 8 hourly intravenously plus Mylanta II 60 ml 2 hourly. The level of treatment required by proportions of the total study group were (1) 15%, (2) 71%, (3) 96%, (4) 100%. Head-injured and intubated patients generally fell in the more resistant group while patients having had major elective surgery required lower levels of therapy. If control of gastric pH is to be uniformly achieved, a technique of titrated therapy based on gastric pH measurements is supported as cheaper and more effective than other standardised treatment regimens.

Adult↗
PubMed1991

Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo.

By modification of a recently developed method for separation of radio-labelled urinary oestrogens we were able to separate oestrogen metabolites and measure their isotope ratios in urine following injections of [3H]delta 4-androstenedione and [14C]oestrone. This method provides a useful tool for studying in vivo aromatisation of delta 4-androstenedione into oestrone in breast cancer patients before and during treatment with aromatase inhibitors.

Aminoglutethimide↗
PubMed1991

Hybrid receptors.

Many hormone and growth factor receptors form homomeric oligomers. Subunits of related receptors can be mixed to form hybrid receptors. These can have novel ligand-binding and signaling properties. The additional flexibility that results from the ability to independently regulate the expression and function of different component subunits greatly increases the spectrum of cellular responses to extracellular signals.

Carrier Proteins↗
PubMed1990

Partial down-regulation of protein kinase C reverses the growth inhibitory effect of phorbol esters on HepG2 cells.

Phorbol ester treatment of HepG2, a human tumorigenic cell line, caused rapid morphological changes characterized by a flattening and spreading of the cells that coincided with a rapid inhibition of thymidine incorporation. Within 24 h, cell division was completely inhibited, suggesting the cells had entered a quiescent state. Continued incubation in the presence of phorbol esters resulted in the resumption of thymidine incorporation and cell division, but this coincided with only a partial down-regulation of PKC activity. Seventy-two hours of treatment was required to obtain down-regulation of greater than 80% of the PKC activity, but reversal of the inhibitory effects occurred between 24 and 48 h after the addition of phorbol esters, when a large proportion of the PKC activity was still present. Northern blot analysis of a number of transcripts showed that the steady-state levels of c-myc and transforming growth factor beta 1 (TGF-beta 1) messages increased only after 3 h of phorbol ester treatment and returned to normal levels after 24 h. C-fos, albumin, and alphafetoprotein messages were not affected, suggesting the differentiation state of the cells was not altered. Therefore, phorbol ester activation of PKC causes an inhibition of HepG2 cell growth initially, but this is unlike the promotion of differentiation seen in other systems. Partial down-regulation of PKC activity causes a reversal of the growth inhibition and the cells return to a normal growth rate. This effect is also clearly different from systems in which phorbol esters have been shown to have a mitogenic effect on cells.

Carcinoma, Hepatocellular↗
PubMed1990

Use of granulocyte-macrophage colony-stimulating factor in patients with malignancy and bone marrow failure.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients with refractory malignancies, 2 patients who had myelodysplastic syndromes with severe neutropenia and to a patient who had delayed marrow recovery after 3 cycles of therapy for acute leukemia. A marked neutropenia and monocytopenia was observed within 5 min after an i.v. injection of GM-CSF. This persisted for 1-2 h and seemed related to activation of an adhesive glycoprotein (MO1) on the surface of these cells. With continued daily i.v. administration of GM-CSF, all patients with refractory malignancies developed a striking leukocytosis. Total leukocyte counts reached 75,000/microliters within 2 weeks of treatment. This was due to an increase in band and segmented neutrophils, eosinophils and monocytes. Accelerated myelopoiesis required the continuous presence of GM-CSF; with pump failure for 24 h or discontinuation after 14 days, leukocyte counts returned to normal levels in 24-48 h. GM-CSF also increased myelopoiesis in the patients with myelodysplastic syndromes or following anti-leukemic treatment. These observations suggest that this growth factor should prove a useful adjunct in the treatment of patients with malignancies and bone marrow failure.

Aged↗
PubMed1990

Limits of reproducibility of cross-sectional echocardiographic measurement of left ventricular ejection fraction.

The total intrinsic variability of echocardiographically determined ejection fraction was evaluated in this study. Cross-sectional left ventricular echocardiograms were made in 14 normal volunteers (9 men, 5 women), ages 31 to 41 years (mean 36 years) with an interval period of about 11 months. We used the parasternal long-axis view, the short-axis view at the papillary muscle level and the four-chamber view from the apex. M-mode recordings were made from the parasternal long-axis view. Simpson's rule and area-length formulas were used to calculate left ventricular volumes and the ejection fraction. From the methods under investigation, the Teichholz technique and the bullet method showed the best reproducibility of the ejection fraction with a coefficient of variation of 4 +/- 3% and 6 +/- 4%, respectively (mean +/- SD). The methods of Baran, and the approach using slices, showed rather large coefficients of variation, 14 +/- 11% and 9 +/- 6%, respectively.

Adult↗
PubMed1990

Down syndrome and low maternal serum alpha fetoprotein.

The early pregnancy maternal serum alpha-fetoprotein (MSAFP) results for 35 patients who delivered a baby with Down syndrome (DS) were analysed. These results were collected from 1981 to mid-1989. Eight of the 35 showed an MSAFP result less than 0.5 multiples of the median (MOM). These MSAFP results were corrected for maternal weight. The results support other workers' conclusions that mid-trimester hormonal analyses may be helpful in diagnosing the presence of DS in women otherwise not considered at risk.

Adult↗
PubMed1990

Depressive episodes and dysphoria resulting from conjugal bereavement in a prospective community sample.

Using three waves of interviews from the New Haven Epidemiologic Catchment Area Program, the authors contrast the extent and nature of depressive episodes and dysphoria between newly bereaved (N = 39) and married (N = 1,047) respondents age 45 and older. Bereavement greatly increased the risk of both conditions. This observation did not appear to be an artifact because psychosocial risk factors were similar for the bereaved and married groups. Bereavement increased the risk for a depressive episode more among respondents who reported no prior dysphoria than among those who did. Among those meeting criteria for depression, the bereaved reported symptoms similar to those of the married group except for significantly fewer reports of guilt.

Adult↗
PubMed1990

The effect of protein kinase-C inhibition on insulin receptor phosphorylation.

The effect of protein kinase-C (PKC) inhibition on insulin receptor phosphorylation in HepG2 cells was analyzed by two-dimensional tryptic phosphopeptide maps. In basal cells, there was one major insulin receptor-derived tryptic phosphothreonine peptide and at least four phosphoserine peptides. Phorbol 12,13-dibutyrate (PDBU) stimulated phosphorylation of the phosphothreonine peptide, some of the basal phosphoserine peptides, and at least one phosphoserine peptide that was not detected in the basal state. Staurosporine completely inhibited the PDBU-mediated phosphorylation. Although staurosporine also inhibited basal phosphorylation of the phosphothreonine peptide, down-regulation of PKC did not, suggesting that PKC does not mediate basal insulin receptor phosphorylation. Insulin treatment resulted in the appearance of four phosphotyrosine peptides. It also stimulated the phosphorylation of at least two phosphoserine peptides. One of these may have been a complex of two or more distinct but poorly resolved phosphopeptides, which was seen in basal cells and a component of which seemed to be stimulated by PDBU. However, neither staurosporine nor down-regulation of PKC diminished insulin-stimulated serine phosphorylation of these peptides, indicating that insulin-stimulated receptor serine phosphorylation did not involve PKC activity. The addition of staurosporine to cells that had been incubated with PDBU resulted in the very rapid decay of phosphorylation of the phosphothreonine-containing peptide, indicating that this site of phosphorylation turns over very rapidly, while some of the other phosphoserine-containing peptides, including the major unique site of phosphorylation stimulated by PDBU, turned over more slowly. Thus, the insulin receptor contains several sites of serine/threonine phosphorylation, some of which are substrates for more than one protein kinase. This may permit complex modulation of insulin receptor functions in response to multiple signalling pathways.

Alkaloids↗
PubMed1990

Anxiety disorders during acute bereavement: risk and risk factors.

Forty-four percent of bereaved spouses reported at least one type of anxiety disorder during the first year of bereavement in a survey of a representative sample composed of a subgroup (N = 48) assessed 6 months after bereavement and another subgroup (N = 54) assessed 12 months after bereavement. The bereaved spouses experienced 6-month prevalence rates for panic disorder and generalized anxiety disorders that were higher than community prevalence rates for the same metropolitan area (p less than .01). Past personal history of anxiety disorder was an independent risk factor (p less than .05), and anxiety disorders were associated with severe grief (p less than .01) and depression (p less than .05). The large overlap of anxiety disorders with major depression observed in this study indicates that the estimated rates of anxiety disorder are not independent of major depression in most cases and raises questions about whether the anxiety disorders of bereavement are prodromal, concomitant, or residual with respect to major depression.

Adult↗
PubMed1989

Insulin-like growth factor I receptor beta-subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers.

In both NIH3T3 cells and HepG2 cells, insulin-like growth factor I (IGF-I) receptors possess two beta-subunits that display different electrophoretic mobilities. Increasing concentrations of IGF-I stimulated the phosphorylation of both beta-subunits to a similar extent, whereas insulin stimulated the phosphorylation of both subunits only at elevated concentrations. Both beta-subunits were immunoprecipitated with p5, an insulin receptor-specific anti-peptide antibody, or with A410, a polyclonal anti-insulin receptor antisera. However, if the tetrameric IGF-I receptor was first dissociated into alpha-beta heterodimers with 1 mM dithiothreitol, only the lower molecular weight beta-subunit was immunoprecipitated. These results suggested that p5 and A410 specifically recognized the lower molecular weight beta-subunit but immunoprecipitated the higher molecular weight beta-subunit because it was present in the same disulfide linked tetramer. Similarly, alpha-IR-3, an antibody specific for the alpha-subunit of the IGF-I receptor, immunoprecipitated both types of beta-subunit from the intact tetramer but only the higher molecular weight beta-subunit from the dissociated heterodimers, suggesting that there are two types of alpha-subunits in the same tetramer and that the alpha-subunit recognized by alpha-IR-3 is only associated with the higher molecular weight beta-subunit. Tryptic phosphopeptide maps of the lower molecular weight beta-subunit of IGF-I receptor were different from the higher molecular weight beta-subunit, but were similar to those of the insulin receptor beta-subunit. Thus, by immunochemical cross-reactivity and structural criteria, the lower molecular weight beta-subunit of the IGF-I receptor was similar to the beta-subunit of insulin receptor. These data suggest that there exists a species of IGF-I receptor that is a hybrid composed of an insulin receptor alpha-beta heterodimer and an IGF-I receptor alpha-beta heterodimer. The existence of such a hybrid receptor could have important functional consequences.

Animals↗
PubMed1989

Antisera to synthetic peptides as probes of structural changes during aging of alpha-crystallin from the bovine lens.

Polyclonal antisera have been made to synthetic peptides of 11-15 residues that correspond to nine different regions of the alpha A crystallins. These antisera have been used in a radioimmunoassay to quantitatively probe for structural and/or covalent changes of alpha-crystallins in the nucleus versus cortex of the adult bovine lens. Antisera specific for the C-terminal and N-terminal regions of the alpha-crystallins bind more to alpha-crystallins from cortex. Antisera to three out of the seven internal sequences (residues 75-89, 87-101 and 135-149) bind better to alpha-crystallins from the bovine lens nucleus, suggesting a greater accessibility of these sequences to antisera binding. Together, these studies demonstrate that antisera against synthetic peptide sequences of alpha A crystallins are very specific probes that can detect structural and/or covalent changes in specified regions of the alpha-crystallins during the process of aging in the bovine lens.

Aging↗
PubMed1989

Prediction of outcome in patients with acute variceal haemorrhage.

Prediction of outcome in 87 patients following acute bleeding oesophageal and gastric varices due to portal hypertension from chronic liver disease was studied at our hospital over a 30-month period. The overall mortality rate was 26 per cent (23/87), with the operative mortality rate (50 per cent) being more than triple the non-operative mortality rate (14 per cent). The initial prothrombin time ratio (PTR) alone was significantly different in survivors and non-survivors both in the operated and non-operated patients. The only survivor in the whole material with a PTR greater than or equal to 2.2 was a patient who was transferred and underwent successful liver transplantation elsewhere. Among operated intensive care unit (ICU) patients, the Glasgow predictor gave a mean probability of discharge of 0.81 (s.d. 0.15) in 13 survivors and of 0.35 (s.d. 0.35) in the 15 non-survivors (P less than 0.001). In the 11 non-operative ICU patients, who had failed sclerotherapy, the Glasgow predictor could not be validated. Fourteen ICU deaths were associated with significant hypotension defined as a systolic blood pressure less than 90 mmHg for greater than 1 h.

Acute Disease↗