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Biomedical subjects

S Jacob

Publications and source records attributed to S Jacob.

At least 127 records · Page 7Linked to original sources
PubMed1997

A dual technique for identification of the epidural space.

A method of identifying the epidural space is described in which the traditional loss of resistance to air technique is combined with amplification of the sound made by the epidural needle as it traverses the interspinous ligament and the ligamentum flavum and then enters the epidural space. The method retains all the advantages of the loss of resistance to air technique whilst, in addition, the auditory amplification gives a slightly earlier warning of entry into the epidural space. The apparatus necessary is readily available and the technique is easy to use. In addition to being useful in difficult epidurals, the technique would also be an excellent teaching aid.

Air↗
PubMed1997

Studies on gastric mucosal microcirculation. 1. The nature of regional variations induced by ethanol injury.

BACKGROUND/AIMS: The focal nature of gastric ulcers raises the possibility of underlying regional disturbances in gastric mucosal microcirculation. This study employed fluorescent in vivo microscopy with the aim of directly investigating the response of several areas of the gastric mucosa to 60% ethanol. METHODS: Changes in macromolecular leakage of fluorescein labelled albumin, vessel diameter, and acridine red labelled leucocyte adhesion and rolling were assessed over a period of two hours. A total of 0.5 ml 60% ethanol was topically applied for five minutes to the exteriorised gastric mucosa of anaesthetised rats. RATS: Three distinct patterns of response were found. Areas of lesion formation were small and occurred within five minutes. These areas showed persistent blood flow stasis throughout the course of the experiment, increased leakage (p < 0.02), and no leucocyte adhesion. Peripheral to the lesion, sustained leakage (p < 0.02) was found with adherence of leucocytes (p < 0.01) after lesion formation. Sites more remote to any lesion showed transient leakage and significant numbers of 'rolling' leucocytes (p < 0.01) were observed again after the lesion had formed. CONCLUSIONS: Despite widespread exposure of the entire gastric mucosa to 60% ethanol the resultant mucosal injury was limited. Widespread vascular damage was found reflected by macromolecular leakage, the pattern of which showed regional variation.

Administration, Topical↗
PubMed1997

Studies on the gastric mucosal microcirculation. 2. Helicobacter pylori water soluble extracts induce platelet aggregation in the gastric mucosal microcirculation in vivo.

BACKGROUND: The exact mechanisms by which Helicobacter pylori infection results in gastric mucosal injury are unclear. AIMS: To assess in vivo whether H pylori extracts could initiate an inflammatory response in the rat gastric mucosal microcirculation. METHODS: Extracts of H pylori, Escherichia coli, or distilled water were administered topically to the gastric mucosa of anaesthetised animals. Fluorescence in vivo microscopy assessed macromolecular leakage of labelled albumin from mucosal vessels, leucocyte adherence/rolling, and platelet activity for 90 minutes. RESULTS: H pylori induced increases (p < 0.001) in adherent platelet thrombi and circulating platelet emboli after five and 15 minutes respectively. Adherent platelet thrombi (mean of four per field of view) remained significantly increased throughout the experiment, but circulating emboli (maximum of five at 30 minutes) decreased with time. Leucocyte adherence did not occur although early transient rolling was observed. An 11% increase (p < 0.02) in albumin leakage occurred after five minutes only. The induction of platelet aggregation was only observed following H pylori administration. CONCLUSION: This in vivo study demonstrated the ability of H pylori extracts to promote platelet aggregation within gastric mucosal microvessels. Recruitment of leucocytes was not observed. The results suggest that the early events associated with H pylori infection are platelet aggregation with perhaps subsequent leucocyte recruitment by activated platelets.

Animals↗
PubMed1997

Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle.

The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin-stimulated glucose metabolism in insulin-resistant humans and animals. We determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA on glucose metabolism in skeletal muscle of an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat. Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA]. Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose oxidation were determined in the epitrochlearis muscles in the absence or presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA. Insulin-stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment, whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R-(+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No significant increase in these parameters was observed after S-(-)-ALA treatment. Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment. Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin-stimulated glucose transport and non-oxidative and oxidative glucose metabolism in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much more effective than the S-(-) enantiomer.

Animals↗
PubMed1997

Insulin resistance, hyperinsulinemia, and blood pressure: role of age and obesity. European Group for the Study of Insulin Resistance (EGIR).

In population surveys, blood pressure and plasma insulin concentration are related variables, but the association is confounded by age and obesity. Whether insulin resistance is independently associated with higher blood pressure in normal subjects is debated. We analyzed the database of the European Group for the Study of Insulin Resistance, made up of nondiabetic men and women from 20 centers, in whom insulin sensitivity was measured by the euglycemic insulin clamp. After excluding subjects aged > or =70 years, those with severe obesity (body mass index [BMI] >40 kg x m[-2]), and those with abnormal blood pressure values (> or =140/90 mm Hg), 333 cases (ages 18 to 70 years; BMI, 18.4 to 39.8 kg x m[-2]) were available for analysis. In univariate analysis, both systolic and diastolic blood pressures were inversely related to insulin sensitivity, with r values of 0.18 (P<.005) and 0.34 (P<.0001), respectively. In a multivariate model simultaneously accounting for sex, age, BMI, and fasting insulin, systolic and diastolic blood pressures were still inversely related to insulin sensitivity (partial r, 0.15 and 0.19; P<.01 for both). In this model, age was positively related to blood pressure levels independently of insulin sensitivity, whereas BMI was not. The predicted impact on blood pressure of a decrease in insulin sensitivity of 10 micromol x min(-1) x kg(-1) was +1.4 mm Hg, similar to that associated with a 10-year difference in age. Although insulin levels and insulin action were reciprocally interrelated, diastolic blood pressure varied as a simultaneous function of both. In normotensive, nondiabetic Europeans, insulin sensitivity and age are significant, mutually independent correlates of blood pressure, whereas body mass is not. The relation of blood pressure to both insulin action and circulating insulin levels is compatible with distinct influences on blood pressure by insulin resistance and compensatory hyperinsulinemia.

Adolescent↗
PubMed1997

Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats.

The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance. In the present study, the effects of chronic in vivo moxonidine treatment of obese Zucker rats--a model of severe glucose intolerance, hyperinsulinemia and insulin resistance, and dyslipidemia--on whole-body glucose tolerance, plasma lipids, and insulin-stimulated skeletal muscle glucose transport activity (2-deoxyglucose uptake) were investigated. Moxonidine was administered by gavage for 21 consecutive days at 2, 6, or 10 mg/kg body weight. Body weights in control and moxonidine-treated groups were matched, except at the highest dose, at which final body weight was 17% lower in the moxonidine-treated animals compared with controls. The moxonidine-treated (6 and 10 mg/kg) obese animals had significantly lower fasting plasma levels of insulin (17% and 19%, respectively) and free fatty acids (36% and 28%, respectively), whereas plasma glucose was not altered. During an oral glucose tolerance test, the glucose response (area under the curve) was 47% and 67% lower, respectively, in the two highest moxonidine-treated obese groups. Moreover, glucose transport activity in the isolated epitrochlearis muscle stimulated by a maximally effective insulin dose (13.3 nmol/L) was 39% and 70% greater in the 6 and 10 mg/kg moxonidine-treated groups, respectively (P<.05 for all effects). No significant alterations in muscle glucose transport were elicited by 2 mg/kg moxonidine. These findings indicate that in the severely insulin-resistant and dyslipidemic obese Zucker rat, chronic in vivo treatment with moxonidine can significantly improve, in a dose-dependent manner, whole-body glucose tolerance, possibly as a result of enhanced insulin-stimulated skeletal muscle glucose transport activity and reduced circulating free fatty acids.

Animals↗
PubMed1997

Cholecystectomy under regional anesthesia in a patient with total Kartagener's syndrome.

A 41-year-old woman with complete Kartagener's syndrome developed cholecystitis in a left-sided gall bladder. Bilateral diffuse bronchiectasis ruled her unfit for general anesthesia; chronic cough, copious expectoration and dyspnea prevented her from lying down supine for more than a few minutes. Successful cholecystectomy was performed in a semi-reclined position using thoracic epidural anesthesia, the anatomy being the mirror image of that of a gall bladder in normal position. The gall bladder was full of stones and operative cholangiogram revealed a normal but transposed biliary system.

Adult↗
PubMed1997

[Gynecologic allergy to spermatic fluid. A case report].

Seminal fluid allergy is a possible diagnosis in front vulvovaginal inflammations occurring rapidly after coitus. The type I reaction (revealed by the immediate hypersensitivity Prick-test) is most frequently encountered. In case of systemic symptoms, the circulating Ig E specific antibodies can be increased. Treatment is palliative (condoms, antihistamines cream). In case of systemic disease, desensibilisation can be proposed. This infrequent but uncomfortable syndrome is also in question in some cases of immunologic infertility.

Adult↗
PubMed1996

Mammalian NUMB is an evolutionarily conserved signaling adapter protein that specifies cell fate.

BACKGROUND: Drosophila numb was originally described as a mutation affecting binary divisions in the sensory organ precursor (SOP) lineage. The numb gene was subsequently shown to encode an asymmetrically localized protein which is required for binary cell-fate decisions during peripheral nervous system development. Part of the Drosophila NUMB protein exhibits homology to the SHC phosphotyrosine-binding (PTB) domain, suggesting a potential link to tyrosine-kinase signal transduction. RESULTS: A widely expressed mammalian homologue of Drosophila numb (dnumb) has been cloned from rat and is referred to here as mammalian Numb (mNumb). The mNUMB protein has a similar overall structure to dNUMB and 67 sequence similarity. Misexpression of mNumb in Drosophila during sensory nervous system precursor cell division causes identical cell fate transformations to those produced by ectopic dNUMB expression. In vitro, the mNUMB PTB domain binds phosphotyrosine-containing proteins, and SH3 domains of SRC-family tyrosine kinases bind to mNUMB presumably through interactions with proline-rich regions in the carboxyl terminus. Overexpression of full-length mNUMB in the multipotential neural crest stem cell line MONC-1 dramatically biases its differentiation towards neurons, whereas overexpression of the mNUMB PTB domain biases its differentiation away from neuronal fates. CONCLUSIONS: Our results demonstrate that mNUMB is an evolutionarily conserved functional homologue of dNUMB, and establish a link to tyrosine-kinase-mediated signal transduction pathways. Furthermore, our results suggest that mNUMB and dNUMB are new members of a family of signaling adapter molecules that mediate conserved cell-fate decisions during development.

Amino Acid Sequence↗
PubMed1996

Role of IL-7 in the shaping of the pulmonary gamma delta T cell repertoire.

Gamma delta T cells bearing the canonical fetal-type V gamma 6/V delta 1 rearrangements are the predominant gamma delta T cells in the lungs of adult mice. In contrast, these V gamma 6/V delta 1 T cells are virtually absent in the pulmonary epithelia of nude mice. The intraepithelial dominance of gamma delta T cells that express this particular TCR is thought to result from a preferred thymic pathway of gene rearrangement and not from TCR-mediated positive selection. We now show that gamma delta T cell precursors in the lung epithelium of both euthymic and athymic neonatal mice generate this rearrangement in situ. In athymic mice, these clonotypes do not survive, but can be rescued in vitro and in vivo by the lymphokine IL-7.

Animals↗
PubMed1996

Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity.

The phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domain of the proto-oncoprotein p52SHC binds to an NPXpY consensus sequence found in several growth factor receptors (Kavanaugh, W. M., Turck, C. W., and Williams, L. T. (1994) Science 268, 1177-1179). The amino-terminal region of p52SHC, which includes the PTB/PI domain, has been previously shown to associate with protein-tyrosine phosphatase-PEST (PTP-PEST) in vivo (Habib, T. , Herrera, R., and Decker, S. J. (1994) J. Biol. Chem. 269, 25243-25246). We report here the detailed mapping of this interaction in a murine context using glutathione S-transferase fusion protein binding studies and peptide competition assays. We show that the interaction between murine SHC and murine PTP-PEST is mediated through the PTB/PI domain of murine SHC and an NPLH sequence found in the carboxyl terminus of murine PTP-PEST. Since this interaction is not dependent on the presence of a tyrosine-phosphorylated residue in the target sequence, this reveals that the PTB/PI domain of SHC can recognize both tyrosine-phosphorylated sequences and non-tyrosine-based recognition motifs.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Comparative disposition of acrylonitrile and methacrylonitrile: quantitative whole-body autoradiographic studies in rats.

Following intravenous administration of an equimolar (0.216 mmol/kg) radioactive dose of acrylonitrile (2-[14C]VCN, 11.5 mg/kg) or methacrylonitrile (2-[14C]MeVCN, 14.5 mg/kg), the tissue distribution, covalent interaction, and elimination were compared (at 5 min to 48 hr) in male Fischer 344 rats using whole-body autoradiography (WBA). Autoradiographs obtained from freeze-dried or acid-extracted sections of animals treated with 2-[14C]VCN showed that radioactivity accumulated in the liver, lung, bone marrow, adipose tissues, kidney, gastrointestinal tract, and spleen. In animals treated with 2-[14C]MeVCN, the respiratory tissues contained high levels of 14C at an early period (5 min), while the gastrointestinal mucosa, adrenal cortex, liver, and kidney contained high levels of radioactivity at later periods (8, 24, and 48 hr). Quantitatively, lower uptake and irreversible interactions of 14C were observed in autoradiographs of rats treated with 2-[14C]MeVCN compared with those treated with 2-[14C]VCN. Rats given 2-[14C]VCN eliminated only 27% of administered radioactivity (exhaled air, urine, and feces), whereas rats treated with 2-[14C]MeVCN eliminated, by all routes, 65% of the total radioactive dose. Both WBA and elimination studies indicated that 2-[14C]VCN and/or its metabolites were rapidly distributed, extensively bound, and slowly eliminated from tissues. 2-[14C]MeVCN and/or its metabolites, however, were rapidly distributed and eliminated, mostly via the lung. The study indicated that the substitution of a methyl group on the alpha-carbon of the alpha-beta unsaturated aliphatic nitrile VCN, to form MeVCN, imparted qualitative and quantitative differences in the disposition of these two compounds.

Acrylonitrile↗
PubMed1996

Modified latex agglutination test for rapid detection of Streptococcus pneumoniae and haemophilus influenzae in cerebrospinal fluid and direct serotyping of Streptococcus pneumoniae.

A modified latex agglutination test was designed and evaluated for the rapid detection of Streptococcus pneumoniae and haemophilus influenzae type b capsular antigens, and for direct serotyping of Streptococcus pneumoniae in the cerebrospinal fluid. Reagents were prepared by sensitizing latex particles with Omniserum (against 83 capsular serotypes of pneumococci) and Haemophilus influenzae type b burro antiserum. For serotyping reagents, latex particles were similarly coated with nine pneumococcal pool (a to I) antisera and 46 individual pneumococcal serogroup/serotype specific antisera. The test was performed on cerebrospinal fluid from 298 patients with suspected meningitis. Serotyping was done directly on untreated cerebrospinal fluid samples showing positive reactions with the Omniserum reagent. Pneumococcal or Haemophilus influenzae type b antigens were detected in 41 patients; in 32 of these the etiology was established by culture and in 2 by smear examination. Five of the remaining seven cases were judged clinically and by cytological examination of cerebrospinal fluid to have partially treated bacterial meningitis. In two cases the test was false positive. The overall sensitivity and specificity of the latex agglutination test for the detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens was 100% and 96.8% respectively. The commonest pneumococcal serotypes were type 1 (30%), types 6 and 19 (10% each). The latex agglutination test is rapid and simple to perform, yielding serotype data directly by testing of cerebrospinal fluid.

Adult↗
PubMed1996

Influence of route of administration on [3H]-camptothecin distribution and tumor uptake in CASE-bearing nude mice: whole-body autoradiographic studies.

Camptothecin (CPT) inhibits the growth of a wide variety of experimental tumors. As a part of our exploration of this drug for use as a cancer chemotherapeutic agent, we studied the effect of route of administration on the absorption, distribution and tumor uptake of [3H]-CPT. The rate of disappearance of [3H]-CPT-derived radioactivity from blood during the first 48 h was highest following oral than following intravenous (i.v.) administration. Thereafter blood levels were low irrespective of route of administration. Considerable [3H]-CPT-derived radioactivity was detected in urine and feces up to 48 h after dosing. Distribution studies were conducted using quantitative whole-body autoradiography (WBA). These studies revealed that independent of the route of administration, [3H]-CPT was rapidly excreted in the bile (gallbladder) followed by elimination into the small and large intestinal tract. Levels of CPT-derived radioactivity in the kidneys were minimal and mostly localized in the renal pelvis. Hepatic concentrations of CPT were low and were almost equal to those of the tumor. The lungs of animals treated i.v. showed higher uptake of radioactivity than those treated intramuscularly or orally. Tumor/blood ratios were slightly higher following oral administration than following administration by other routes. This study indicates that CPT is primarily eliminated via the bile. The gastrointestinal tract is the major site of accumulation and excretion of CPT.

Administration, Oral↗
PubMed1996

Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle.

We have used an animal model of insulin resistance-the obese Zucker (fa/fa) rat-to test whether oral administration of the non-sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, trandolapril, alone or in combination with the Ca2+-channel blocker, verapamil, can induce a beneficial effect on insulin-stimulated glucose transport and metabolism in skeletal muscle. Insulin-stimulated 2-deoxyglucose (2-DG) uptake in the isolated epitrochlearis muscle was less than 50% as great in obese animals compared with lean (Fa/-) controls (P < .05), but was significantly improved in the obese group by both short-term (6 hours, +33%) and long-term (14 days,+70%) oral treatment with trandolapril. Verapamil treatment alone did not alter insulin-stimulated 2-DG uptake in muscle, but simultaneous administration of verapamil and trandolapril resulted in the most pronounced effect on insulin-stimulated 2-DG uptake (+106%). Long-term treatment with trandolapril alone and in combination with verapamil significantly increased muscle glycogen (+26% to 27%), glucose transporter GLUT-4 protein (+27% to 31%), and hexokinase activity (+21% to 49%), and decreased plasma insulin levels (-23% to -29%). Muscle citrate synthase activity was enhanced only when trandolapril and verapamil were administered in combination (+24%). We conclude that the long-acting, non-sulfhydryl-containing ACE inhibitor, trandolapril, alone and in combination with the Ca2+-channel blocker, verapamil, can significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat, and that this improvement is associated with favorable adaptive responses in GLUT-4 protein levels, glycogen storage, and activities of relevant intracellular enzymes of glucose catabolism.

Angiotensin-Converting Enzyme Inhibitors↗