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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 19 recordsLinked to original sources
PubMed1992

Use of compounds naturally labeled with stable isotopes for the study of the metabolism of glycoprotein neutral sugars by gas-liquid chromatography-isotope-ratio mass spectrometry. Technical validation in the rat.

In order to develop an alternative method to radioactive labeling for the study of the glycoprotein sugar metabolism in man, the possible use of stable isotopes provided by naturally, 13C-enriched dietary compounds has been explored in rat intestine and serum. Rats were fed a semisynthetic diet containing 67% wheat starch (containing 1.08692 13C atom/100 carbon atoms) for a week, and then the same diet containing corn starch (1.10042% 13C) for a week. Neutral sugars were prepared from delipidated, trichloroacetic acid-precipitable material from 200-400 mg of intestinal mucosa or 1 mL of serum, separated, and analyzed as alditol acetates by gas-liquid chromatography coupled to isotope-ratio mass spectrometry. This technique allowed the determination, in a single experiment, of the amount and 13C abundance of six neutral sugars (including xylose used as internal standard). Despite the low abundance of 13C in natural products, the sensitivity of the technique was found to be sufficient to detect isotopic enrichment as low as 0.001% with good accuracy and reproducibility in 2 micrograms of each glycoprotein neutral sugar. As an example, the pattern of labeling by dietary D-glucose from corn starch appears to be very different for fucose, ribose, mannose, galactose, and glucose of intestine or serum macromolecules.

Animals↗
PubMed1992

Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T.

The envelope protein of the human immunodeficiency virus (gp120) causes neuronal death in developing murine hippocampal cultures or rat retinal ganglion cells. In HIV-infected individuals, gp120 released from HIV-infected macrophages or other cells in the brain has been proposed as the etiology for the pathophysiology of AIDS central nervous system (CNS) disease by diffusing to act at a distance to cause damage and/or death to neighboring neurons. In this study, 28 cerebrospinal fluid (CSF) samples from HIV-infected individuals (79% were WR stage 1 and 2) and neurological disease controls were tested, blind to the investigator, for the presence of in vitro neuronal killing activity. Neurotoxic activity was detected with peak effects at a 1:10(5) dilution in CSF from 9/18 HIV-infected individuals and 1/10 neurological disease controls. Thus half of CSF from early stages of HIV disease are characterized by the presence of neurotoxic activity which is not present in control CSF (Fischers exact test, P < 0.05). The neuronal toxicity by patient CSF could be prevented by peptide T (1 nM). A monoclonal antibody to mouse CD4, RL.172, also attenuated or prevented CSF-induced neuronal killing in all four CSF samples tested. In addition, an antiserum to peptide T previously shown to bind gp120 and neutralize both infectively and direct gp120 neurotoxicity, neutralized the CSF factor. gp120, or a modified small fragment, is suggested to be the responsible toxic molecular entity. These results may be relevant to the pathophysiology of HIV-related CNS disease and the mechanism by which peptide T causes improvements.

Animals↗
PubMed1992

Effects of endogenous soluble beta-galactoside binding lectins and protein inhibitor of fucosyltransferase on the enzymes involved in the intestinal fucosylation process.

Soluble beta-galactoside binding lectins were prepared from the rat small intestinal mucosa by chromatography on asialofetuin-Sepharose. The lectin fraction exhibits 3 bands with Mr of 21,5 kDa, 19 kDa and 17 kDa on SDS-PAGE. This fraction inhibits a partially purified soluble alpha(1-2)-fucosyltransferase by interaction with the glycoprotein substrate asialofetuin, whereas the inhibition is non competitive for the donor GDP-fucose. It has no effect on other enzymes of the fucosylation system, namely glycosyl-nucleotide pyrophosphatase and the system synthesizing GDP-fucose from GDP-mannose. A different and specific soluble protein inhibitor of fucosyltransferase activity inhibits this activity by a competitive mechanism for GDP-fucose and a non competitive one for asialofetuin. Unlike the lectins, this inhibitor also inhibits the action of pyrophosphatase and the formation of GDP-fucose by different mechanisms. The possible extension of these in vitro results to the in vivo regulation of glycosylation is discussed.

Animals↗
PubMed1992

Effects of okadaic acid on the activities of two distinct phosphatidate phosphohydrolases in rat hepatocytes.

Incubation of hepatocytes with okadaic acid displaced the N-ethylmaleimide-sensitive phosphatidate phosphohydrolase from the membrane fraction into the cytosol and partially prevented the oleate-induced movement of phosphohydrolase from cytosol to membranes. However, higher concentrations of oleate still caused translocation and activation of the phosphohydrolase. This enzyme is stimulated by Mg2+, and is probably involved in glycerolipid synthesis. Okadaic acid also decreased the concentration of diacylglycerol within the hepatocytes. Okadiac acid had no observable effect on the activity of an N-ethylmaleimide-insensitive phosphatidate phosphohydrolase which remained firmly attached to membranes. This activity is not stimulated by Mg2+ and is probably involved in signal transduction by the phospholipase D pathway.

Animals↗
PubMed1992

Lateralized mediation of arousal and habituation: differential bilateral electrodermal activity in unilateral temporal lobectomy patients.

The purpose of the present study was to increase our understanding of the differential hemispheric processing of arousal and habituation. Subjects were unilateral temporal lobectomy patients and controls. Each was exposed to an arousal/habituation task consisting of a series of tones and an auditory discrimination paradigm. Electrodermal activity was recorded from the left and right hands throughout. Results provide evidence for a state of hypoarousal in right temporal patients and some support for hyperarousability in lefts. This is consistent with data showing that right hemisphere damage is associated with inattention and denial and left hemisphere damage with hypervigilance and anxiety. The concept of laterally differentiated mediation of arousal and habituation was supported.

Adult↗
PubMed1992

Use of polyglactin 910 knitted mesh tubing to stabilize particulate hydroxyapatite in alveolar ridge augmentation. A preliminary report.

A universal problem with the use of hydroxyapatite (HA) particles has been the tendency for these particles to migrate beyond planned boundaries. This is a preliminary report on the use of polyglactin 910 knitted mesh (Vicryl) tubing containing HA particles in ridge-augmentation procedures, assessing the technique and the containment of HA particles. The technique is described and experience with six cases is presented. This study found no clinical or radiographic evidence of particle migration after normal function had been resumed. In one case the graft failed to become firmly incorporated with the bone and the whole graft migrated anteriorly on the mandible but still provided improved function for the patient. The technique facilitates the placement of HA particles and would be particularly useful if open mucosal flap techniques were being used for ridge augmentation. The use of Vicryl tubing for HA augmentation procedures prevents the migration of particles and allows an easier and more accurate placement of the grafts.

Adult↗
PubMed1992

Protection of glomerular filtration rate by the thromboxane receptor antagonist L655,240 during low dose cyclosporine administration.

Cyclosporin A (CsA) alters the production of prostaglandins (PG) by the kidney. CsA causes an increase in renal vascular resistance, a decrease in renal blood flow, a decrease in glomerular filtration rate (GFR), and increases the renal production of the vasoconstrictor thromboxane. Recently, low dose CsA has been utilized in the treatment of refractory autoimmune diseases. To determine if low dose CsA administration could produce renal hemodynamic alterations and to determine if the thromboxane receptor antagonist L655,240 could prevent these alterations, we administered groups of rats either CsA, 5 mg/kg, subcutaneously and the L655,240 vehicle NaHCO3 (CsA-NaHCO3), or CsA and L655,240 (CsA-L655,240), or CsA vehicle and L655,240. The rats were administered the drugs for 7 days and then subjected to inulin and PAH clearances or kidneys were harvested for prostaglandin production studies. CsA significantly depressed GFR and renal plasma flow when compared to the L655,240 treated groups. There was no difference in inulin or PAH clearance between the CsA-L655,240 and CsA vehicle L655,240 groups. Glomerular prostaglandin production including thromboxane was depressed by CsA administration. No histologic alterations were noted in the glomeruli or the medullary portions of the kidney. We conclude that administration of low dose CsA, 5 mg/kg, for 7 days results in a decrease in renal blood flow and GFR without histologic alterations. Administration of the thromboxane receptor antagonist L655,240 prevents the renal hemodynamic alterations induced by CsA in this rat model.

Animals↗
PubMed1992

Nutritional and developmental regulation of glycosylation processes in digestive organs.

We review the nutritional and developmental variations of the glycosylation processes in digestive organs, since glycoproteins play a prominent part as mucins or digestive enzymes in these tissues. The biosynthesis of the glycannic chains is demonstrated to be largely sensitive to various exogenous (such as nutritional) or endogenous (such as developmental) factors. Although the metabolic regulation by dietary variations appears as rather complex, according to the variety of experimental conditions and the diversity of the organs studied, available data demonstrate that this regulation does exist, depending on the quantity or sometimes the quality of the major or minor components of the diet, which induce significant variations in the glycosylation processes. The synthesis of the internal core of N-glycans is essentially regulated by diet-induced variations of the phosphoryl-dolichol level, whereas the modulation of the biosynthesis of the external part of N-glycans or the biosynthesis of O-glycans is controlled by diet-induced variations in the systems transferring fucose, galactose, sialic acid or hexosamines. Modifications in intestinal glycosylation during post-natal development in the rat control the quality of the glycannic chains of mucins and brush-border enzymes. The post-natal maturation of the intestinal rat tissue is characterized by a shift from sialylation to fucosylation, depending on coordinate changes in glycosyltransferase activities, in sugar-nucleotide breakdown or synthesis or in the activity of regulatory proteins. These activities are largely sensitive to dietary manipulations at weaning and to hormonal stimulations before weaning. However, glucocorticoid hormones do not appear as the triggering signal for the induction of these changes.

Animals↗
PubMed1992

Post-mortem toxico-kinetics of trazodone.

Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5-20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants.

Female↗
PubMed1992

Polymerase chain reaction for detection of verocytotoxigenic Escherichia coli isolated from animal and food sources.

Animals and their by-products have been implicated as important sources of verocytotoxigenic Escherichia coli (VTEC) associated with disease in humans. VTEC comprise a wide range of serotypes and produce a variety of closely related verocytotoxins (VT). A pair of oligonucleotide primers, targeting conserved sequences found in VT1, VT2 and VTE genes, was used to develop a polymerase chain reaction (PCR) procedure to detect all types of VTEC. Supernatants of boiled broth cultures of VTEC (223 strains) isolated from ground beef, ground pork, raw milk, bovine faeces and porcine faeces; non-VTEC E. coli (72 strains); and other enteric and food bacteria (76 strains) were tested by PCR. The verocytotoxigenicity of these strains was verified by the Vero cell assay. All 223 VTEC isolates, comprising over 50 different serotypes, were detected by the PCR procedure. Shigella dysenteriae type 1 was the only other bacterium that was positive in this assay. As little as 1 pg of VTEC DNA and as few as 17 cfu of VTEC could be detected with this method. The results indicate that these primers detect VTEC over a wide range of serotypes. This method may be applicable as a screening procedure for the detection of VTEC in samples of foods and faeces.

Animals↗
PubMed1992

Monoclonal antibody AMH152 reacts with human monocytes in culture and with inflammatory macrophages.

Monoclonal antibodies (mAb) raised against human peritoneal macrophages were selected for their non-reactivity with freshly sampled blood cells. One of these mAb, AMH152, initially non-reactive, bound to monocytes after 18 h of culture, a property which was not shared by an unrelated antibody of the same isotype (IgG1). The induction of the expression of the antigen detected by AMH152 on monocytes in culture was not influenced by the addition of serum or by the substrate used, plastic that favoured adhesion or teflon bags. Overnight incubation at 4 degrees C in adhesion conditions did not enable antigen expression. A 1-h treatment with phorbol myristate acetate or formyl-methionyl-leucyl-phenylalanine did not increase AMH152 binding. Culturing monocytes with cycloheximide tended to inhibit antigen expression. These observations suggested that antigen expression represents an active phenomenon, requiring protein synthesis. The antigen recognized by mAb AMH152 could be visualized on sections of formalin-fixed and paraffin-embedded tissues. Macrophages of healthy lymphoid organs and tissues that expressed CD68 antigen failed to bind AMH152. In contrast, chronic inflammatory lesions, like those of sarcoidosis, tuberculosis and cat scratch disease, contained epithelioid and multinucleated giant cells that reacted with AMH152. In serous exudates of cancer metastases, 10-40% of macrophages were also stained. The antigenic material was essentially present at the cell periphery. Thus, mAb AMH152 recognized a surface antigen, detectable on paraffin-embedded tissue sections, and which accompanied differentiation of monocytes into inflammatory cells. The expression of this antigen on monocytes in culture suggests that these cells underwent an activation process, even when maintained for some hours in teflon bags and in a serum-free medium.

Antibodies, Monoclonal↗
PubMed1992

[Analgesic effect of ibuprofen in pain after episiotomy].

The relief of post-episiotomy pain was investigated in three groups of women, ranked ASA 1 or 2, using either a single dose of 400 mg of ibuprofen (n = 31), or 1 g of paracetamol (n = 28) or placebo (n = 31). Pain intensity was assessed with a visual analogic scale, a verbal scale and pain relief scores after half an hour, 1, 2, 3, 4, 5 and 6 h. The day after treatment, patients rated the quality of pain relief, and were asked whether they wished to take again the same drug for the same type of pain. In the placebo and paracetamol groups, respectively 22 and 16 patients asked for usual treatment before the sixth hour, whereas only 5 did so in the ibuprofen group (p less than 0.001). Ibuprofen was more effective after one hour than either of the other two drugs, whatever the scale or parameter used. In the ibuprofen group, the lower pain score was observed at the third hour. At six hours, the pain score did not differ from that three hours earlier. On the day after treatment, 22 patients from the ibuprofen group considered pain relief to have been good or excellent, versus 8 and 5 in the paracetamol and placebo groups respectively (p less than 0.001). Similarly, 24 patients from the ibuprofen group would accept the same drug again for the same type of pain, as opposed to 8 and 5 from the paracetamol and placebo groups respectively (p less than 0.01). The only side-effect reported was abdominal pain in one patient (placebo group).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1992

Monoclonal antibody AP-282 recognizes a marker for human polymorphonuclear granules.

Hybridoma AP-282 was produced by fusing mouse plasmacytoma cells with splenocytes of mice immunized against purified human polymorphonuclear cells. The secreted monoclonal antibody (MAb), AP-282, a mouse IgG1, was found to react strongly with all neutrophilic granulocytes, their bone marrow precursors, weakly with blood monocytes and not with eosinophils. The antigen was resistant to formalin fixation but was destroyed by exposure to fixatives containing acetic acid. Using the APAAP technique, antibody AP-282 strongly labelled neutrophils on sections of frozen cut or paraffin embedded tissues. No staining was seen of non hematopoietic tissues. AP-282 recognized an internal antigen associated to cytoplasmic granules. Chemical investigations on dot blots of whole or of purified cellular extracts indicated that the antigen idenfied by MAb AP-282 was different from those recognized by usual antigranulocyte antibodies, i.e. myeloperoxidase, elastase, cathepsin G and lactoferrin. Thus, antibody AP-282 constitutes a new cytoplasmic marker of neutrophils.

Animals↗
PubMed1992

T cells and human autoimmune thyroid disease: emerging data show lack of need to invoke suppressor T cell problems.

Human T cells recognize self and foreign antigens when such antigens are processed into small peptides and bound to molecules coded for by genes of the HLA region on chromosome 6. The part of the T-cell surface which is responsible for such recognition is a set of molecules coded for by a variety of genes and known as the T-cell-receptor complex. In animal models, T cells are able to transfer autoimmune thyroiditis and T cells have, therefore, long been implicated in the etiology of human autoimmune thyroid disease (AITD). Information gained from the study of intrathyroidal T cells and thyroid antigen-specific T-cell clones has shown that in patients with Graves' disease, mainly helper T-cell clones have been obtained, whereas in autoimmune (Hashimoto's) thyroiditis cytolytic T-cell clones may be predominant. Such thyroid antigen-specific T cells have now been shown to recognize one or other of the three major thyroid-specific antigens; thyroglobulin, thyroid peroxidase, or the TSH receptor and efforts are currently in progress to characterize the T-cell epitopes of these major thyroid autoantigens. Recent findings of restricted T-cell receptor V gene use amongst intrathyroidal T cells confirm the primary role of T cells in human thyroid autoimmune processes leading to AITD. However, the mechanisms whereby such autoreactive T cells escape deletion and anergy, and how they become activated, remain uncertain. There is compelling evidence that the thyroid cell itself, by expressing HLA molecules, and presenting antigen directly to the T cells, may initiate disease, perhaps after an external insult.

Amino Acid Sequence↗
PubMed1992

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Adult↗
PubMed1992

A phase II trial of continuous infusion cisplatin and 5-fluorouracil with oral calcium leucovorin in colorectal carcinoma.

Twenty previously untreated patients with advanced colorectal adenocarcinoma were entered on a Phase II trial of 3-day continuous infusion cisplatin (25 mg/m2/day) and 5-fluorouracil (800 mg/M2/day) with oral calcium leucovorin (30 mg/dose) every 6 hours. There were four partial responses (20%) and two complete responses (10%) for a total response rate of 30% (95% confidence limits +/- 20%). Patients received a median of 4.5 cycles of therapy (range 2-9 cycles). Three patients experienced neutropenia; one had a life-threatening infection. One developed neuropathy at 375 mg/M2 cumulative dose. Four patients developed mucositis. Treatment was stopped for one patient with stable disease after 5 cycles because of anorexia and nausea and vomiting; treatment was stopped for four patients because of excessive fatigue. The median duration of responses was 4 months (range 3-6 months). Although this regimen is active, the response rate, cumulative nature of the toxicity, and the requirement for hospitalization led us to conclude that this regimen does not warrant Phase III testing but might be a basis for further Phase II therapeutic trials.

Administration, Oral↗