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Biomedical subjects

A George

Publications and source records attributed to A George.

At least 109 records · Page 6Linked to original sources
PubMed1995

Escherichia coli O157 infection associated with a farm visitor centre.

During the summer of 1994, four cases of bloody diarrhoea and/or haemolytic uraemic syndrome were reported to the consultants in communicable disease control in Nottingham and Leicester. One case was an adult, and there were three children aged 2 to 4 years. The initial investigation failed to reveal any common foodstuff as the cause of the outbreak, but all four cases had attended a farm visitor centre in Leicestershire in the three weeks before they became ill. A further three cases were found who had visited the same farm. A joint investigation took place with environmental health officers and the local veterinary investigation centre of the Ministry of Agriculture, Fisheries and Food. A questionnaire designed to ascertain possible sources of infection was sent to all cases. Several of the animals on the farm were sampled for Escherichia coli O157 and the farm's facilities for food preparation and hygiene were assessed. The pattern of infection did not suggest a point source for the outbreak. Analysis of responses to the questionnaires failed to reveal any common factor other than the visit to the farm, and all but one case remembered stroking and feeding the animals. Food preparation in the farm restaurant appeared to be satisfactory and there was no evidence of contamination of food with pathogenic bacteria. E. coli O157: H7, PT2, VT2 was isolated from four of the seven human cases and also from four cattle and six goats. Further analysis using restriction fragment length polymorphism (RFLP) showed that the four human strains were indistinguishable from nine of the 10 animal strains. It was concluded that the most likely cause of this outbreak was direct contact with the animals. This was further supported by poor handwashing facilities and lack of information for the visitors on the importance of personal hygiene.

Adolescent↗
PubMed1995

In situ hybridization shows Dmp1 (AG1) to be a developmentally regulated dentin-specific protein produced by mature odontoblasts.

Acidic phosphorylated proteins are prominent constituents of the extracellular matrix of bone and dentin. It has been postulated that they may have important structural and regulatory roles in the process of tissue mineralization. Studies of a cDNA library, prepared from cells of the rat incisor odontoblast-pulp complex of 3 week old Sprague-Dawley rats, led to the identification of a serine-rich acidic protein, designated AG1, which appeared to be a dentin matrix component. In order to determine which cells of the odontoblast-pulp complex were responsible for the making of AG1, in situ hybridization was carried out using digoxigenin-labeled probes. The full length AG1 cDNA was subcloned into the pBluescript vector, which contains two strong promoters, T3 and T7. The sense and antisense complementary RNA (cRNA) hybridization probes were prepared by in vitro transcription using T3 and T7 polymerases in the presence of 11-dUTP. Incisor sections were obtained from rat embryos at days 16, and 20, and newborns at days 2 and 5. No AG1 mRNA was detected in the embryonic sections, but digoxigenin labeling was evident in odontoblasts secreting mineralizing dentin at postnatal days 2 and 5. Sense probes showed no hybridization. Pulp cells, Meckel's cartilage, and alveolar bone were free of hybridization with the antisense probe. Unexpectedly, a low level of digoxigenin staining was seen in the cytoplasm of secretory ameloblasts, but not in the preameloblasts, stratum intermedium or stellate reticulum of the enamel organ. These data show that AG1 expression is regulated developmentally and is restricted to secretory stage mature odontoblasts.

Alveolar Process↗
PubMed1995

Effect of polymyxin B nonapeptide on daptomycin permeability and cell surface properties in Pseudomonas aeruginosa, Escherichia coli, and Pasteurella multocida.

The present study was carried out to determine if sensitization of Gram-negative bacteria to the polyanionic antibiotic daptomycin by cationic molecules can be explained on the basis of decreased cell surface charge in order to better understand intrinsic resistance. Turbidimetric assessments of batch cultural growth kinetics revealed the outer membrane permeabilizer polymyxin B nonapeptide sensitized Pseudomonas aeruginosa and Escherichia coli to the hydrophobic probe novobiocin, whereas little or no sensitization was observed for two surface hydrophobicity variants of Pasteurella multocida. Polymyxin B nonapeptide and daptomycin synergistically inhibited growth of P. aeruginosa only. A hydrocarbon adherence assay revealed permeabilizing concentrations of polymyxin B nonapeptide increased cell surface hydrophobicity of P. aeruginosa and the hydrophobic P. multocida variant, while E. coli and the hydrophilic P. multocida variant remained unaffected. Measurement of cellular electrophoretic mobility showed polymyxin B nonapeptide permeabilization of P. aeruginosa to daptomycin occurred concomitantly with a significant decrease in cell surface charge, while no such sensitization occurred in organisms which failed to undergo polymyxin B nonapeptide-induced surface charge decreases. These data suggest that sensitization of Gram-negative bacteria to polyanionic lipopeptides by growth in the presence of polycationic outer membrane permeabilizers such as polymyxin B nonapeptide is dependent on diminution of overall cell surface charge and polarity, thereby allowing outer cell envelope permeation.

Cell Membrane↗
PubMed1994

Predicting protein crystallization from a dilute solution property.

A dilute solution parameter obtained from static light-scattering measurements is proposed as a predictor for protein crystallization experiments. The osmotic second virial coefficients, B(22), have been measured for a variety of proteins in solvents that are known to promote crystallization and the values for B(22) were found to lie within a fairly narrow range which we refer to as a crystallization slot. Solution conditions which were known not to favor crystallization of the proteins resulted in B(22) values well outside the crystallization slot.

Journal Article↗
PubMed1994

Ligation of CD45 on B cells can facilitate production of secondary Ig isotypes.

The possibility that isotype switching in B cells may be affected by engagement of the CD45 molecule on B cells has been investigated in microcultures containing limiting numbers of B cells and nonlimiting numbers of both alloreactive Th cells and purified dendritic cells (DC). Addition of Abs to the B cell-specific isoform, B220, to the microcultures leads to an increase in the proportion of B cell clones that secrete secondary Ig isotypes. In the presence of anti-CD45 Ab, microculture wells show a 39% frequency of secondary isotypes (560/1440) compared with a 11% frequency in control microcultures (89/780). Cross-linking appears to enhance this effect. Even in cultures of B cells and DC without T cells, addition of anti-B220 induces isotype switching in a significant number of microwells. Cross-linking and capping B220 molecules results in co-capping of surface Ig and MHC class II molecules. The results suggest that signal transduction through the CD45 molecule may affect pathways involved in isotype switching.

Animals↗
PubMed1994

Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride.

Current treatment strategies for levodopa-induced psychosis in Parkinson's disease have had limited success. Remoxipride, a selective D2 receptor antagonist, was administered in an open label pilot study to seven parkinsonian patients exhibiting thought disorder. Symptoms improved significantly in six patients after treatment durations of 1-6 months and cleared completely in two individuals. One patient (at age 90 the oldest in the group) could not tolerate the compound due to significant motor deterioration, and the drug had to be discontinued after 1 week. In all remaining patients, no motor complications appeared, and therapeutic effects of remoxipride continued for up to 3 months after treatment cessation and have lasted for 2 years now in one individual. Further study of this compound in the context of treatment-induced psychosis in Parkinson's disease appears to be warranted.

Aged↗
PubMed1994

Use of tobacco and alcoholic beverages by children and teenagers in a low-income coastal community in south India.

To plan and implement cancer control measures, information about the baseline habit patterns of the community is needed. A coastal village near Trivandrum, Kerala, Southern India, supported mainly by the fishing industry, was identified for this study with regard to establishing measures to control oral cancer there. Oral cancer is prevalent in Kerala. Smoking and chewing tobacco and drinking alcoholic beverages are the major risk factors for this cancer. The socioeconomic status of the fishermen of Kerala is low and their literacy rate is low. The adults in coastal Kerala have been found to have a habit pattern of very high levels of tobacco and alcohol use. A survey was conducted to study the tobacco and alcohol use habits of 146 children and teenagers in this village. The percentages of study subjects with pan-tobacco-chewing, smoking, and drinking habits were 29%, 2%, and 3%, respectively. The habit pattern correlated negatively with education and positively with number of children per family. This survey provides information that can be used to plan cancer education efforts, including redesigning the school curriculum and focusing on high-risk groups.

Adolescent↗
PubMed1994

Biased TCR gene usage in alloreactive T cells specific for a structurally dissimilar MHC alloantigen.

Two models of allorecognition of MHC molecules have been proposed. One emphasizes specificity for MHC molecule-bound peptides and the other for exposed MHC polymorphisms. We predicted that the latter model would predominate in responder:stimulator combinations whose MHC molecules differed extensively in their TCR-contacting surfaces and that this would be reflected in biased TCR usage. Two panels of anti-DR11 T cell clones were generated, one from a DR17 and the other from a DR15 responder. The TCR-contacting surfaces of DR17 and DR11 have multiple differences, and those of DR15 and DR11 are very similar. TCR analysis by polymerase chain reaction amplification and mAb staining revealed that five out of nine DR17 anti-DR11 clones used the V beta 13 and two the V beta 6, family. In contrast seven different V beta families were used by the eight DR15 anti-DR11 clones. A similar bias in TCR V beta usage was observed in the polyclonal DR17 and DR11 T cell lines from which the clones were derived, and in a second DR17 anti-DR11 line from a different individual. These results support the concept that specificity for the foreign MHC structure itself may play an important role in the alloresponse between responders and stimulators with structurally dissimilar MHC molecules.

Amino Acid Sequence↗
PubMed1994

In situ localization and chromosomal mapping of the AG1 (Dmp1) gene.

Dentinogenesis is being used as a model for understanding the biomineralization process. The odontoblasts synthesize a structural matrix comprised of Type I collagen fibrils which define the basic architecture of the tissue. The odontoblasts also synthesize and deliver a number of dentin-specific acidic macromolecules into the extracellular compartment. These acidic macromolecules may be involved in regulating the ordered deposition of hydroxyapatite crystals within the matrix. AG1 is the first tooth-specific acidic macromolecule to have been cloned and sequenced. To identify which cells of the rat incisor pulp/odontoblast complex were responsible for synthesis of AG1, in situ hybridization was used. Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared. The AG1 mRNA was found to be expressed in the mature secretory odontoblasts. Neither pulp cells nor pre-odontoblasts showed any staining with the anti-sense probes. Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5. AG1 has been renamed Dmp1 (dentin matrix protein 1) in accordance with present chromosomal nomenclature. Mouse 5q21 corresponds to the 4q21 locus in humans. This is the locus for the human tooth mineralization disorder dentinogenesis imperfecta Type II (DI-II). These data suggest that the Dmp1 gene is involved in mineralization and is a candidate gene for DI-II.

Animals↗
PubMed1994

Altered cortisol response and hippocampal atrophy in pediatric HIV disease.

The hippocampus is a major center for the regulation of the hypothalamic-pituitary-adrenal axis. There is experimental evidence that chronic exposure to high levels of glucocorticoids may be toxic to the hippocampus. We observed elevated mean basal and 60-min cortisol (F) levels in response to adrenocorticotropin stimulation (0.25 mg cortrosyn, i.v. bolus infusion) in 15 children with HIV infection. Furthermore, in eight of the children for whom data was available, in addition to high peripheral cortisol levels, neurologic dysfunction and hippocampal atrophy were noted on CT scan. These preliminary data suggest that in HIV-infected children an altered cortisol secretion may be associated with specific central nervous system damage.

Adolescent↗
PubMed1993

Characterization of a novel dentin matrix acidic phosphoprotein. Implications for induction of biomineralization.

Acidic phosphorylated proteins have been shown to be prominent constituents of the extracellular matrix of bone and dentin. The acidic phosphoproteins of bone contain more glutamic acid than aspartic acid and a lower serine content than either. On the other hand, the major dentin acidic phosphoproteins, phosphophoryns, have been defined as aspartic acid- and serine-rich proteins, with a lesser content of glutamic acid. Both sets of phosphoproteins have been implicated as key participants in regulating mineralization, but it has been difficult to unify their mechanisms of action. We have now identified, by cDNA cloning, a new serine-rich acidic protein of the dentin matrix, AG1, with a composition intermediate between the bone acidic proteins and dentin phosphophoryns. AG1 has numerous acidic consensus sites for phosphorylation by both casein kinases I and II. Immunochemical and organ culture biosynthetic studies show that AG1 is present in phosphorylated form at low levels in the dentin matrix. If fully phosphorylated, AG1 would bear a net charge of -175/molecule of 473 residues. AG1 contains single RGD integrin binding and N-glycosylation sequences. The overall picture that emerges is that of a matrix-associated acidic phosphoprotein, with a potentially high calcium ion binding capacity, present at levels compatible with a regulatory role in dentin mineralization.

Amino Acid Sequence↗
PubMed1993

Efficacy of phenelzine and haloperidol in borderline personality disorder.

OBJECTIVE: To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. PATIENTS: One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. INTERVENTIONS: Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. MAIN OUTCOME MEASURES: Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). RESULTS: Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. CONCLUSIONS: Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

Adult↗
PubMed1993

Status of nitric oxide free radicals in diabetic neutrophils: effect of diabetic serum factor on the generation of these species in normal neutrophils and their relation to lysosomal degranulation.

Normal polymorphonuclear leukocytes (PMNL) in contrast to diabetic PMNL, generated significant amounts of .NO and NO2 when challenged with opsonised zymosan. Diabetic neutrophils, on the other hand, responded either weakly or insignificantly to the same stimulants. However, in resting state the levels of .NO and NO2 were higher in diabetic as compared to normal PMNL. Diabetic serum factor (DSF) provoked a significant generation of .NO and NO2 in normal PMNL, a phenomenon found parallel to the enhancement in cytosolic cathepsin D activity in normal cells on insult with DSF.

Biological Factors↗