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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 307 records · Page 17Linked to original sources

The cellular functions of small GTP-binding proteins.

A substantial number of novel guanine nucleotide binding regulatory proteins have been identified over the last few years but the function of many of them is largely unknown. This article will discuss a particular family of these proteins, structurally related to the Ras oncoprotein. Approximately 30 Ras-related small guanosine triphosphate (GTP)-binding proteins are known, and from yeast to man they appear to be involved in controlling a diverse set of essential cellular functions including growth, differentiation, cytoskeletal organization, and intracellular vesicle transport and secretion.

Animals↗

Ascaris lumbricoides: detecting its metabolites in the urine of infected people using gas-liquid chromatography.

Substances dissolved in the urine of people infected with Ascaris lumbricoides were extracted and detected by gas-liquid chromatography. The ratios of the areas of the peaks produced by two substances extracted from urine to the area of the peak of solvent were found to be significantly correlated with the worm burden. A chemical analysis of the predominant substance by infrared spectrophotometry and proton magnetic resonance spectrometry indicated that it was 2-methyl-butyramide. The chemical properties of the other substance indicated that it was 2-methyl-valeramide. These substances are likely to be derivatives of two acids known to be end products of the carbohydrate metabolism of Ascaris.

Amides↗

Aqueductal (pencil) glioma presenting as neurogenic pulmonary edema: a case report.

A case of neurogenic pulmonary edema due to hydrocephalus, without initial neurological deficit, is described. Computed tomography demonstrated a ring enhancing lesion in the tectum of the mesencephalon obstructing the aqueduct of Sylvius. The lesion, on autopsy, was a rare mesencephalic glioma described in the literature as a "pencil glioma" of the aqueduct.

Adult↗

Influence of inorganic lead on the biochemical blood composition of the eel, Anguilla anguilla L.

Yellow eels (Anguilla anguilla L.) with an average weight of 50 g were caught in September in the Aveiro Lagoon on the Portuguese West Coast and kept in aerated aquaria for 1 week before the experiment started. The eels were exposed to an inorganic lead concentration of 300 micrograms Pb/liter for 30 days. Differential white blood cell count showed an increase in the number of lymphocytes in exposed fish. Blood hemoglobin and number of red blood cells per cubic millimeter showed no differences between the control and the exposed fish. Biochemical analyses of blood composition, such as plasma glucose, total plasma protein, total plasma cholesterol, and sodium and potassium plasma, showed no differences between treated and control animals. Plasma lactate levels increased in treated animals compared with those in controls.

Animals↗

Metabolic effects of kraft mill effluents on the eel Anguilla anguilla L.

Yellow eels (Anguilla anguilla L.) with an average weight of 60 g were used in this experiment. The fish were caught in June/July at the Aveiro Lagoon on the Portuguese West Coast, transported to the Department of Biology, Aveiro University, and kept in aerated aquaria for 1 week before the experiment started. The eels were then exposed for 1 and 3 weeks to 75 and 50% of the kraft pulp mill effluent. The eels exposed to the kraft pulp mill effluent developed an increase in red blood cell number per cubic millimeter and several biochemical changes, such as an increase in plasma lactate and sodium and a decrease in plasma pyruvate and potassium. Histological examination of the experimental eels exposed to the 50% kraft pulp mill effluent revealed deep alteration of the tissue structure, such as disruption of the skin and edematous hypertrophy of covering epithelial cells in secondary gill lamellae. The kidney had damage of the renal tubules. The liver developed necrosis supported by a significant decrease in GOT and GPT activity. The spleen had an increase in blood content as well as in pigment centers. Previous results indicated the kraft pulp mill effluent causes tissue damage and consequent metabolic changes in the eel Anguilla anguilla L.

Alanine Transaminase↗

Glutathione S-transferase (placental) as a marker of transformation in the human cervix uteri: an immunohistochemical study.

Using an indirect immunohistochemical technique on paraffin sections, employing a polyclonal antibody to the acidic (placental) form of glutathione-S-transferase (GST), we have evaluated cytoplasmic and nuclear staining in a series of 67 cervical biopsies including normal non neoplastic tissue, immature squamous metaplasia, all grades of cervical intraepithelial neoplasia (CIN) and invasive carcinomas of keratinising and non-keratinising types. No differences in cytoplasmic staining between the varied lesions studied were seen. However, there were marked differences in nuclear staining. While normal non-neoplastic stratified squamous epithelium showed weak staining of the lower one-third of the epithelium only, in immature squamous metaplasia and in all grades of CIN there was intense nuclear staining in all layers of the epithelium. Invasive carcinomas showed generally less intense nuclear staining than CIN lesions. Endocervical cell nuclei also showed intense nuclear staining. These findings indicate that GST is of limited use as a marker of transformation in the human cervix uteri.

Biomarkers, Tumor↗

Zymodemes of Entamoeba histolytica in Dhaka, Bangladesh.

Stool samples containing Entamoeba histolytica were obtained from two sources: an urban hospital and an urban slum. Using the enzyme patterns of three enzymes (E.C.2.7.1.1 hexokinase, E.C.5.3.1.9 glucose phosphate isomerase and E.C.2.7.5.1 phosphoglucomutase) stained after cellulose acetate electrophoresis, four zymodemes (I, II, XIV and XVI) were identified in 71 isolates. Zymodemes considered to be pathogenic (II and XIV) were identified from 31 of 34 isolates from the urban hospital, and these zymodemes were strongly associated with dysentery and trophozoites containing ingested red blood corpuscles. Blood visible to the naked eye was more commonly seen in stools from which zymodeme XIV was isolated than in those containing zymodeme II (P less than 0.001). Zymodemes considered to be non-pathogenic (I and XVI) were identified in 34 of 37 isolates from slum dwellers and were not associated with blood in the stools.

Animals↗

Microinjection of recombinant p21rho induces rapid changes in cell morphology.

The rho proteins, p21rho, are ubiquitously expressed guanine nucleotide binding proteins with approximately 30% amino acid homology to p21ras, but their biochemical function is unknown. We show here that microinjection of constitutively activated recombinant rho protein (Val14rho) into subconfluent cells induces dramatic changes in cell morphology: 15-30 min after injection cells adopt a distinct and novel phenotype with a contracted cell body and finger-like processes still adherent to the substratum. Ribosylation of Val14rho with the ADP-ribosyltransferase C3 from clostridium botulinum, before microinjection, renders the protein biologically inactive, but it has no effect on either its intrinsic biochemical properties or on its interaction with the GTPase activating protein, rho GAP. Micro-injection of ribosylated normal rho, on the other hand, has a similar effect of injection of C3 transferase and induces complete rounding up of cells. We also report striking biochemical changes in actin filament organization when contact-inhibited quiescent 3T3 cells are injected with Val14rho protein. The effects induced by activation or inactivation of p21rho described here, suggest that the biological function of this protein is to control some aspect of cytoskeletal organization.

Adenosine Diphosphate Ribose↗

Differential effects on cell killing in metallothionein overexpressing CHO mutant cell lines.

An increased level of metallothionein (MT) within the cytosol has been associated with the development of resistance to the cytotoxic effects of alkylating agents, but the mechanism of this effect is unclear. To verify the possible role of MT as a direct scavenger of alkylating agents we transfected two alkylating agent sensitive CHO mutant cell lines, methyl methanesulphate-1 and -2 (MMS-1 and MMS-2), with the human metallothionein II-A (hMTII-A) gene. From each mutant two transfected cell clones were isolated which were found to bear episomally 50 to 70 copies of the plasmid pMTII-BPV coding for the hMTII-A gene. The transfected cell lines contained between 1.4 and 4.9 micrograms of MT per 10(7) cells. This could be increased 2- to 9-fold by heavy metal induction. Transfectants derived from mutant MMS-1 were equally sensitive as the parental cells to a set of alkylating agents. However, transfectants derived from mutant cell line MMS-2 gained significant resistance to both N-methyl-N'-nitro-N-nitrosoguanidine and N-nitroso-N-methylurea, whilst retaining sensitivity to MMS. The degree of resistance was not increased by MT induction after heavy metal ion exposure. These results indicate that although resistance to alkylating agents may be mediated by a process which involves MT expression, this is not due to simple scavenging of the cytotoxic agent by the MT protein.

Animals↗

Purification and characterization of a pi class glutathione S-transferase from human leukaemic cells.

The glutathione S-transferases are a group of enzymes involved in the detoxification of a wide range of xenobiotics. Elevation of the level of activity of glutathione S-transferases within the cytosol has been associated with the development of resistance to a number of cytotoxic drugs, including some commonly used in the treatment of leukaemia. In this paper we describe the purification and characterization of an anionic (p class) form of the enzyme from the peripheral blood of patients with acute myeloid leukemia, chronic myeloid leukaemia, and acute lymphocytic leukaemia and the spleen of a patient with chronic lymphocytic leukaemia. We present evidence that the form of enzyme purified closely resembles pi class glutathione S-transferase purified from human placenta. Immunoblotting performed on cytosol from the leukaemic cells from a range of cases of leukaemia at presentation, or on treatment, demonstrated that this form of glutathione S-transferase was the predominant isoenzyme expressed in all cases studied. However, in the limited number of cases studied there was no correlation between the level of expression and response to chemotherapy, suggesting that increased expression of pi class GST is not the sole cause of resistance to bifunctional alkylating agent in human leukaemias.

Aged↗

Unusual presentation of a monomorphic adenoma.

This case is presented as an example of the diagnostic difficulty that can be associated with radiolucencies around the apices of teeth. The discovery of a monomorphic adenoma within bone was unexpected because of its very rare occurrence.

Adenoma↗

Opinions of Botswana dental therapists and students about their professional education.

This paper presents an evaluation of the training programme for dental therapists in Botswana. It describes the impetus for the creation of the training programme and its content provided by the principles of Primary Health Care. The opinions of the students and serving dental therapists were investigated through self-complete questionnaires. Both groups wished to develop advanced restorative skills and wanted more time to be allocated to that section of the course which would allow this. In contrast, their interest was less in other sections of the course more specifically concerned with the principles of Primary Health Care, such as the development of communication skills. It is suggested that the findings reflect a confusion about the practice of Primary Health Care.

Attitude of Health Personnel↗

The replicable dimensions of the Beck Depression Inventory.

Numerous studies have focused on the factor structure of the Beck Depression Inventory (BDI) because its underlying structure, once identified, may improve our conceptualizations of the cognitive processes in depression. These studies have produced a wide range of interpretations for the BDI, yet the replicability of these factor solutions across independent samples has not been demonstrated. In this study, a series of factor analyses were conducted that involved the use of a new factor matching procedure (FACTOREP), and both depressed patient and normal population samples. The results supported the presence of a large general factor only, which suggests that the items of the BDI are tapping a general construct of depressive symptoms rather than the variety of more specific constructs suggested by previous researchers.

Adult↗

Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase.

Animals↗

Expression and characterization of the Ha-ras p21 protein produced at high levels in the insect/baculovirus system.

Normal and mutated cDNAs of Ha-ras have each been cloned into a standard (pAc373) and a novel (p36C) baculovirus transfer vector and introduced via homologous recombination into the genome of Autographa californica nuclear polyhedrosis virus immediately downstream of the polyhedrin promoter. Spodoptera frugiperda cells infected with recombinant virus containing the normal Ha-ras gene express very high levels of ras p21 protein (approximately 20% of total cell protein), whereas the mutant protein was expressed at considerably lower levels. Molecular analysis showed that this was most likely due to a post-transcriptional event. The expression vector p36C produced considerably higher levels of recombinant p21 compared to the more commonly used pAc373. The majority of the normal ras p21 protein is soluble, cytoplasmic, and appears to be nonacylated. However, about 10% of the p21 associates with the membrane fraction of infected cells and migrates as a slightly faster band on gels. Furthermore, this band is sensitive to hydroxylamine treatment and shows specific incorporation of [3H]palmitate, strongly suggesting that it is the palmitoylated form of p21, which is the biologically active form of the protein. Both the soluble and membrane-associated p21 have been purified to homogeneity under nondenaturing conditions, the latter in the presence of detergents. The isolation of native palmitoylated p21 has not been reported previously. The difference in hydrophobicity between these two proteins has been demonstrated by Triton X-114 partitioning. The use of the insect/baculovirus expression system to express relatively high levels (20 mg/liter) of palmitoylated p21 should aid experiments to resolve the structural and functional properties of this molecule.

Amino Acid Sequence↗

Possible role of inhibition of glutathione S-transferase in the partial reversal of chlorambucil resistance by indomethacin in a Chinese hamster ovary cell line.

We have reported previously the isolation and characterization of a Chinese hamster ovary cell line, designated CHO-Chlr, which exhibits resistance to bifunctional nitrogen mustards while maintaining sensitivity to a range of other alkylating agents and chemotherapeutic drugs. This enhanced drug resistance is associated with a greater than 40-fold increase in the level of expression of an alpha class (YcYc) glutathione S-transferase (GST) as compared to the parental, CHO-K1, cell line. Here, we have purified GST from CHO-Chlr cells and show that the nonsteroidal antiinflammatory drug indomethacin acts as an inhibitor of enzyme activity. Indomethacin at 500 microM causes no significant decrease in colony forming ability of either CHO-K1 or CHO-Chlr cells. However, the cytotoxicity of chlorambucil is potentiated 5.5-fold in CHO-Chlr cells, but only 2.5-fold in CHO-K1 cells following preexposure to 500 microM indomethacin. In contrast, the antiinflammatory agent acetylsalicylic acid failed to inhibit the activity of purified GST and caused no potentiation of chlorambucil toxicity, suggesting that the potentiation by indomethacin is not due to the effects of this drug on prostaglandin synthesis. These studies provide further evidence that GSTs may be involved in the development of resistance to bifunctional alkylating agents and suggest that indomethacin, or agents with similar activities, may be of value as an adjunct to chemotherapy in some patients with tumors resistant to treatment with alkylating agents.

Animals↗