Search PubMed⌕ Search

Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 559 records · Page 31Linked to original sources
PubMed1991

Plasma membrane fractions from rat liver contain a phosphatidate phosphohydrolase distinct from that in the endoplasmic reticulum and cytosol.

Assays for two distinct phosphatidate phosphohydrolase activities were established based upon a differential inhibition by N-ethylmaleimide (NEM). The activity that is insensitive to this reagent in rat liver is predominantly in the plasma membrane fraction, whereas the NEM-sensitive activity is in the cytosolic and microsomal fractions. The NEM-insensitive activity is further distinguished from the NEM-sensitive phosphohydrolase by: (a) being relatively stable to heat; (b) not being inhibited by phenylglyoxal, butane-2,3-dione, cyclohexane-1,2-dione, 2,4-dinitrofluorobenzene, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and diethyl pyrocarbonate; (c) being inhibited by NaF and phosphatidylcholine; and (d) not being stimulated by Mg2+. The NEM-insensitive activity was specific for phosphatidate. Both phosphohydrolase activities could be inhibited by chlorpromazine, propranolol, sphingosine, and spermine. The NEM-sensitive phosphatidate phosphohydrolase activity was increased by incubating hepatocytes for 12 h with glucagon and dexamethasone, and this effect was antagonized by insulin. The NEM-sensitive phosphohydrolase is concluded to be involved in glycerolipid synthesis. The activity of the NEM-insensitive phosphohydrolase was not altered by preincubation of rat hepatocytes in the short or long term with vasopressin, glucagon, insulin, triiodothyronine, or dexamethasone, but it might be modulated indirectly by sphingosine. The NEM-insensitive enzyme of the plasma membranes could be involved in signal transduction via the agonist-stimulated degradation of phosphatidylcholine through the phospholipase D pathway.

Animals↗
PubMed1991

Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status.

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.

AIDS Dementia Complex↗
PubMed1991

Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA.

5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway. cDNA clones for the human erythroid ALAS isozyme were isolated from a fetal liver library. It can be deduced that the erythroid ALAS precursor protein has a molecular weight of 64.6 kd, and is similar in size to the previously isolated human housekeeping ALAS precursor of molecular weight 70.6 kd. The mature mitochondrial forms of the erythroid and housekeeping ALAS isozymes are predicted to have molecular weights of 59.5 kd and 64.6 kd, respectively. The two isozymes show little amino acid identity in their N-terminal signal sequences but have considerable sequence identity in the C-terminal two-thirds of their proteins. An analysis of the immediate promoter of the human erythroid ALAS gene revealed several putative erythroid-specific cis-acting elements including both a GATA-1 and an NF-E2 binding site. An iron-responsive element (IRE) motif has been identified in the 5'-untranslated region of the human erythroid ALAS mRNA, but is not present in the housekeeping ALAS mRNA. Gel retardation experiments established that this IRE motif formed a protein - RNA complex with cytosolic extracts from human K562 cells and this binding was strongly competed with IRE transcripts from ferritin or transferrin receptor mRNAs. A transcript of the ALAS IRE, mutated in the conserved loop of the IRE, did not readily form this protein - RNA complex. These results suggest that the IRE motif in the ALAS mRNA is functional and imply that translation of the mRNA is controlled by cellular iron availability during erythropoiesis.

5-Aminolevulinate Synthetase↗
PubMed1991

Three-dimensional structure of a mouse-adapted type 2/type 1 poliovirus chimera.

The crystal structure of V510, a chimeric type 2/type 1 poliovirus, has been determined at 2.6 A resolution. Unlike the parental Mahoney strain of type 1 poliovirus, V510 is able to replicate in the mouse central nervous system, due entirely to the replacement of six amino acids in the exposed BC loop of capsid protein VP1. Significant structural differences between the two strains cluster in a major antigenic site of the virus, located at the apex of the radial projection which surrounds the viral five-fold axis. Residues implicated in the mouse-virulence of poliovirus by genetic studies are located in this area, and include the residues which are responsible for stabilizing the conformation of the BC loop in V510. Despite evidence that this area is not involved in receptor binding in cultured primate cells, the genetic and structural observations suggest that this area plays a critical role in receptor interactions in the mouse central nervous system. These results provide a structural framework for further investigation of the molecular determinants of host and tissue tropism in viruses.

Animals↗
PubMed1991

Statistical analysis of the extended Hansen method using the bootstrap technique.

In this study, simple bootstrap techniques are combined with the extended Hansen solubility approach to calculate biases, standard errors, and confidence limits of the partial solubility parameters and to obtain bias-corrected values for these solubility parameters. The bootstrap method is rather new in its application to problems in the pharmaceutical sciences and, therefore, is described here in some detail. This method provides measures of the statistical variation of ratios of regression coefficients without making unwarranted assumptions about data variability. The bootstrap can be used in many statistical packages such as MINITAB, SPSS, SAS, BMDP, or GLIM, all of which are widely available, and could be useful in other areas of the pharmaceutical sciences where regression analysis is employed.

Computer Simulation↗
PubMed1991

Gastric fluid volume and pH in elective patients following unrestricted oral fluid until three hours before surgery.

This clinical study was designed to assess the results of new preoperative fasting guidelines in which patients are instructed that they must not eat any solid food after midnight, but that they may drink unrestricted amounts of clear fluid until three hours before their scheduled time of surgery. We studied 199 healthy, elective surgical inpatients aged 18-70 yr to determine whether there was any correlation between the ingestion interval or the volume of fluid ingested, with the volume and pH of residual gastric fluid at induction of anaesthesia. Pregnant patients, and those with gastric disorders or who were taking medications that affect gastric motility or secretion, were excluded. Either no premedication was given, or oral diazepam 5-15 mg was given 90 min preoperatively. Of the 199 patients, 105 ingested 50-1200 ml on the morning of surgery. The ingestion-induction interval was less than three hours in 12 patients whose actual surgery time was ahead of schedule. The remaining 94 patients did not drink because they were scheduled for surgery before 11:00 (n = 51), they did not want to drink (n = 24), or they were advised not to drink by their nurse or surgeon (n = 16). Following induction of anaesthesia, gastric fluid was aspirated through a #18 Salem sump orogastric tube, the volume was recorded and pH was measured with a calibrated pH meter. Patients were divided retrospectively into four groups (in three of which patients ingested fluid) according to the ingestion-induction interval (1.3-3.0 hr, 3.1-5.0 hr, 5.1-8.0 hr, and nothing by mouth after midnight).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Use of type 1/type 2 chimeric polioviruses to study determinants of poliovirus type 1 neurovirulence in a mouse model.

We previously described the characteristics of a type 1/type 2 (PV-1/PV-2) chimeric poliovirus, v510, which contains the six amino acids specific for PV-2 in the B-C loop of VP1. This virus was found to be mouse-adapted, as PV-2 and in contrast with PV-1. Determinants of host range were studied in detail and are reported here. PV-1/PV-2 chimeras containing partial PV-1----PV-2 substitutions in the B-C loop of VP1 were obtained by making use of a mutagenesis cartridge on PV-1 cDNA. Analysis of mouse neurovirulence of these chimeras, when correlated with the three-dimensional structure of the v510 capsid, revealed that PV-2 residues important for mouse tropism are those which determine the particular conformation of the B-C loop of VP1 in v510. The mutation of the adenine residue at position 480 of the 5' noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys. We show that introduction of this mutation in the v510 genome results in a virus which is partially attenuated for mice. This suggests that analysis of genomic determinants important for PV-1 neurovirulence could be carried out in a mouse model by making use of a mouse-adapted PV-1/PV-2 chimera.

Amino Acid Sequence↗
PubMed1991

The SCID-hu mouse and thyroid autoimmunity: characterization of human thyroid autoantibody secretion.

Severe combined immunodeficient (SCID) mice were injected with peripheral blood mononuclear cells (PBMC) from normal individuals and 14 out of 18 had detectable serum human (h) IgG (maximum levels providing a mean +/- SEM 934 +/- 213 micrograms/ml) and IgM (253 +/- 93 micrograms/ml) at 3-6 weeks after transplantation. Serum human immunoglobulin levels were maximum 6-12 weeks after transplantation and declined to low levels over the subsequent 5 months. Human B cells constituted up to 10% and human T cells up to 40% of cells in the peripheral circulation and spleens of these animals 2-3 weeks after transplantation, PBMC, or intrathyroidal (IT) lymphocytes, from 6 patients with Graves' disease and high serum levels of thyroid autoantibodies were transplanted into 30 SCID mice (Graves' SCID-hu). Although serum human immunoglobulins were observed in only low amounts in the animals receiving IT lymphocytes (n = 4), increased levels of hIgG or hIgM were more easily detectable in 19 Graves' SCID-hu mice that received PBMC. The Graves' SCID-hu mice had significantly lower mean levels of hIgG and hIgM than those observed following transplantation of normal PBMC (mean maximum 328 +/- 113 and 32 +/- 21 micrograms/ml, respectively). Six of these 19 mice had detectable human autoantibody to thyroid peroxidase (TPO, as microsomal antigen) between 3 and 8 weeks after transplantation, with titers ranging from 0.05 to 0.39 (normal SCID-hu serum less than 0.02 ELISA Index). No abnormal thyroid hormone (T4 and T3) levels or thyroiditis was seen when compared to normal SCID-hu mice. Immunization of reconstituted SCID mice with recombinant immunoactive human TPO antigen failed to initiate anti-TPO in normal PBMC-treated mice nor did it increase the titer of human anti-TPO in the anti-TPO positive animals. In conclusion we successfully established human thyroid autoantibody secretion in the SCID-hu mouse and characterized the transient nature of the model. Further studies will be required to achieve successful antigen presentation in this system.

Animals↗
PubMed1991

Inhibition of gastric acid secretion reduces zinc absorption in man.

Numerous factors seem to affect zinc absorption. Gastric acid secretion has been demonstrated to facilitate iron absorption. The zinc tolerance test (ZTT with ZnSO4 220 mg p.o.) was performed in 11 healthy volunteers to study the effects of administering the acid secretion inhibitor cimetidine (1 g/day p.o. for 3 days) and to evaluate the influence of HCl gastric secretion on zinc absorption in physiological conditions. Zinc absorption was reduced after cimetidine administration (p less than 0.005), suggesting that gastric pH influences zinc absorption. To rule out any direct effect of the drug on zinc absorption in five other healthy adults we further evaluated zinc absorption by using a different H2 antagonist (ranitidine 300 mg/day for 3 days and 300 mg before the test). Cimetidine was also tested in these subjects at half the dosage administered to the first group of subjects. Gastric acidity was monitored at 60-min intervals throughout the test via a nasogastric tube. The areas under the plasma concentration curves for zinc were significantly reduced after ranitidine (p less than 0.01), but not after cimetidine administration. Gastric acid was also reduced after ranitidine, but not after cimetidine (500 mg) administration, suggesting that gastric acid secretion plays a role in the regulation of zinc absorption in man.

Adult↗
PubMed1991

Induction of ovulation in rabbits with pure urinary luteinizing hormone and human chorionic gonadotrophin: comparison of oocyte and embryo quality.

Thirty-six 18-week-old nulliparous does were stimulated with a single dose of 25 IU pregnant mare serum gonadotrophin (PMSG). Ovulation was induced 48 h later with 50 IU luteinizing hormone (LH) (18 does) or 50 IU human chorionic gonadotrophin (HCG) (18 does) in order to determine the effects of pure urinary LH and HCG on the quality of oocytes and embryos. Nine does were mated in each group. The does were slaughtered 24 h after induction of ovulation to recover oocytes and 48 h after mating to recover embryos. The number of haemorrhagic, preovulatory and luteinizing follicles per ovary were recorded. The quality of oocytes and embryos recovered were evaluated. No significant differences in the number of haemorrhagic follicles (blood follicles without stigma), preovulatory and luteinizing follicles were observed between LH and HCG groups. LH has a selective action, which could permit the acquisition of better quality oocytes. Although the fertilization rate was similar in both groups (LH versus HCG), the percentage of degenerate embryos (grade 5) was lower for the LH (3%) than the HCG (13%) groups.

Animals↗
PubMed1991

The effect of cyclosporine on agonist-stimulated glomerular and mesangial cell vasodilatory prostaglandin production.

Cyclosporine A administration produces an increase in renal vascular resistance and a decrease in glomerular filtration rate in both human and animal models. CsA usage in humans has also been shown to alter the ability of the kidney to adapt to alterations in renal hemodynamics. CsA alters the production of prostaglandins by isolated rat glomeruli. Normally, vasoconstrictive agents stimulate the production of vasodilatory glomerular and mesangial cell PG. To determine if CsA alters glomerular and mesangial cell (MC) vasodilatory PG production in response to vasoconstrictive agents, we administered CsA, 20 mg/kg, or vehicle to rats for 7 days, or incubated mesangial cells with CsA 1 mcg/ml for 24 hr. Ex vivo glomerular PGE2 and 6-keto-PGF1a production was determined in the presence or absence of angiotensin II 10(-6) M and norepinephrine 10(-5)M. CsA administration decreased glomerular production of both eicosanoids in the basal and stimulated state. Incubation of MC with CsA markedly suppressed PGE2 and 6-keto-PGF1a production in response to stimulation with 200 nM angiotensin II. To determine if CsA inhibits angiotensin II-stimulated PG production prior to protein kinase C, we incubated glomeruli and MC with the diacylglycerol mimetic OAG. CsA depressed OAG-stimulated glomerular and MC PGE2 and 6-keto-PGF1a production. Conversely, CsA stimulated the production of PGE2 by renal medullary slices. We conclude that CsA blunts the vasoconstrictor-induced increase in glomerular and mesangial cell vasodilatory PG production, thereby removing a compensatory mechanism that maintains GFR in states of vasoconstrictor excess.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Analysis of neutralization-escape mutants selected from a mouse virulent type 1/type 2 chimeric poliovirus: identification of a type 1 poliovirus with antigenic site 1 deleted.

A chimeric type 1/type 2 poliovirus (v510), in which the antigenic site 1 (Ag1) of poliovirus type 1 (PV-1) Mahoney was replaced by the corresponding site of poliovirus type 2 (PV-2) Lansing, is known to be neurovirulent for mice and neutralized by both type 1 and type 2 monoclonal antibodies. Neutralization-escape mutants to monoclonal antibodies specifically recognizing the PV-2 sequence were obtained from v510. The nucleotide sequence and the mouse neurovirulence of mutants were determined. Amino acid substitutions obtained inside the replaced sequence, at positions 95 and 99, and outside this site, at positions 93 or 104, rendered the virus attenuated for mice. One of the escape mutants harboured a deletion of the entire substituted nonapeptide sequence in v510. This particular virus, which is a PV-1 Mahoney lacking the natural Ag1 loop, does not react with PV-2-specific monoclonal antibodies, has a ts phenotype, is heat-labile and is devoid of neurovirulence for mice.

Amino Acid Sequence↗
PubMed1991

Psychiatric diagnoses in ulcerative colitis. A controlled study.

Fifty patients with UC and 50 matched controls with urolithiasis were interviewed with the SADS (lifetime version) and completed the SCL-90. According to information given during the SADS, there was a history of psychiatric disturbance in 11 UC patients (22%) and 8 controls (16%). At the time of the interview a psychiatric disturbance was present in 31 UC patients (62%) and four controls (8%), the most frequent diagnoses in the former being minor depression and generalised anxiety disorder. Patients with UC scored significantly higher than the controls on all the different SCL-90 subscales.

Adolescent↗
PubMed1991

[Characterization and postnatal evolution of an endogenous protein inhibitor of intestinal fucosyltransferase activities].

An endogenous protein inhibitor was shown to act in vitro on small intestinal fucosyl-transferase activities. In order to support the hypothesis of a physiological role in vivo for this inhibitor in the regulation of the fucosylation process, we characterized this inhibitor and studied its postnatal development. This inhibitor acts differently upon the enzymes of intestinal fucosylation processes. Among the different organs analyzed, the inhibitor was found only in the intestine and the pancreas. Intestinal inhibitory activity decreased 10 fold between the 7th and the 24th day of rat postnatal development; this decrease was inversely correlated with intestinal fucosyl-transferase activities. Two mechanisms of action by which the inhibitor could exert a physiological regulatory role are discussed.

Animals↗