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Biomedical subjects

J Potter

Publications and source records attributed to J Potter.

At least 109 records · Page 6Linked to original sources
PubMed1991

Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia.

Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucrase-isomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.

Antibodies, Monoclonal↗
PubMed1990

Memory formation in the chick depends on membrane-bound protein kinase C.

The role of protein kinase C (PKC) in the formation of memory for a one-trial passive avoidance task in 1-day-old chicks has been studied, following earlier observations that training on this task results in transient and lateralised changes in the phosphorylation state of presynaptic B-50 protein, a PKC substrate. In accord with hypotheses that the activity of PKC is regulated by translocation from cytosol to membrane, a significant increase was found in the fraction of the alpha/beta forms of the enzyme, assayed immunologically, present in a synaptic-membrane-bound, Triton-extractable form in the left intermediate medial hyperstriatum ventrale (IMHV) of chicks 30 min after training on the passive avoidance task. Two inhibitors of PKC, melittin (10 microliters, 120 microM) and H7 (10 microliters, 10 mM), if injected intracerebrally 10 min prior to or 10 min after training, were without effect on the general behaviour of the chicks or their training. However, these injections of the inhibitors produced amnesia in birds tested 3 h later. This effect was lateralised; only left hemisphere injections of the inhibitors produced amnesia. A possible state-dependency interpretation of these results was ruled out. The results are discussed in the context of hypotheses as to the regulatory role of PKC in neural plasticity and memory formation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Limited proteolysis and 'in vitro' mutagenesis of bovine brain inositol monophosphatase identifies an N-terminal region important for activity.

Bovine brain inositol monophosphatase is rapidly cleaved by endoprotease lys-C at a single site in the absence of SDS. Further sites are revealed only after prolonged incubation with high concentrations of protease. The initial cleavage occurs near one end of the enzyme, generating an N-terminally-derived 36-residue peptide, which is blocked, and a large 28 kDa fragment bearing a free N-terminus. The start sequence of this fragment was found to be Xaa-Ser-Pro-Ala-Asp-Leu-Val, consistent with the cDNA sequence, and Lys-36-Ser-37 was identified as the cleavage site. The activity of the cleaved enzyme was markedly decreased to 3% of that of the native enzyme, although its dimeric structure was preserved. The 36-residue peptide was not covalently associated with the large fragment after proteolytic cleavage, although the possibility of non-covalent association could not be excluded. Finally, the epitope for the inhibitory monoclonal antibody G-2A4 [Gee, Howell, Ryan & Ragan (1989) Biochem J. 264. 793-798] was found to lie proximal to the endoprotease lys-C cleavage site. In vitro mutagenesis further mapped the epitope for monoclonal antibody G-2A4 to residues around Cys-8 of the enzyme. These results suggest that the N-terminal region of the enzyme is important for activity.

Amino Acid Sequence↗
PubMed1990

Cloning and expression of bovine brain inositol monophosphatase.

Inositol monophosphatase is a key enzyme of the inositol phosphate second messenger signaling pathway. It is responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Using oligonucleotide probes based on partial amino acid sequence data for the bovine brain enzyme, several overlapping cDNA clones of 2-3 kilobases in length have been isolated. All contain an open reading frame encoding a 277-amino acid protein. No significant sequence homology was found with any known protein. The open reading frame was inserted into a bacterial expression vector in order to confirm the presumed identity of the protein. The expressed protein reacted with an anti-inositol monophosphatase monoclonal antibody. In addition, the protein was enzymically active and indistinguishable from the bovine brain enzyme with respect to Km values for substrate and Li+ sensitivity of inositol 1-phosphate hydrolysis.

Amino Acid Sequence↗
PubMed1990

Gender, social support and recovery from depressive disorders: a prospective clinical study.

One hundred and thirty men and women attending psychiatric hospitals with depressive disorders were interviewed at the time of their initial contact. After a mean four month interval, 119 were reassessed in order to test the hypothesis that initial levels of social support predict clinical improvement even when other potential risk factors such as age, sex, diagnosis and severity of depression are controlled. Severity and duration of the episode emerged as the only significant background predictors of recovery. The explained variance in recovery from depression due to social support was equal in men and women, and was not diminished by the background clinical predictors. According to subset analyses however, the aspects of personal relationships and perceived support that predict recovery in men and in women appear to be different. The available multiple regression models of outcome favoured a main effect of social support and provided persuasive if inconclusive evidence for a statistical interaction effect with sex. The implications for further research and for theory are discussed.

Adult↗
PubMed1990

Effects of the amnesic agent 2-deoxygalactose on incorporation of fucose into chick brain glycoproteins.

The interaction of the amnesic agent 2-deoxygalactose with fucose incorporation into glycoproteins in day-old chick forebrain has been studied with the aim of identifying glycoproteins whose synthesis is modified during memory formation. 2-Deoxygalactose inhibited total exogenous [14C]fucose incorporation into the forebrain glycoproteins by 26%. Sodium dodecyl sulphate-polyacrylamide gradient gel analysis revealed that intracerebrally injected 2-[3H]deoxygalactose labelled the same eight major glycoprotein bands as were identified using [14C]fucose labelling. Subsequent investigations focussed on these selected components. Subcellular fractionation showed that between 4 and 24 h after administration of the deoxy-sugar, the incorporated radioactivity was found predominantly at the synaptic sites, some glycoproteins being more abundant in synaptic plasma membranes and others in postsynaptic densities. This distribution pattern varied according to the time after injection. The effect of passive avoidance training, using a methylanthranilate-coated bead, on [14C]fucose incorporation into forebrain was to decrease fucose uptake into components of molecular mass 150-180 kilodaltons but to increase significantly labelling of glycoproteins of molecular mass 33 and 28 kilodaltons. The possible implications of these training-induced changes are discussed.

Amnesia↗
PubMed1989

Suppression of human lymphocyte chemotaxis and transendothelial migration by anti-LFA-1 antibody.

The role of lymphocyte function-associated antigen 1 (LFA-1) in human T cell chemotaxis was investigated by using mAb specific to the beta-chain (TS1/18) (CD18) and alpha-chain (TS1/22) (CD11a) of LFA-1. T cell chemotaxis in response to IL-2 and to lymphocyte chemotactic factor (LCF) was markedly suppressed by the addition of TS1/18. TS1/22 was a less effective inhibitor than TS1/18 with only LCF stimulated responses showing significant inhibition when compared in seven different T cell preparations. Neither TS1/18 nor TS1/22 antibody inhibited random T cell migration. Control mAb to CD4 T cells failed to inhibit T cell random migration or chemotaxis. Additional studies to evaluate the adherence and migration of T cells through IL-1-stimulated human umbilical vein endothelial cell (HUVEC) monolayers showed that both TS1/22 and TS1/18 suppressed T cell migration through HUVEC, but failed to inhibit adherence of T cells to these cells. These studies indicate that LFA-1 plays a role in the migration of T cells through HUVEC and in the in vitro chemotactic response of T lymphocytes to IL-2 and LCF.

Animals↗
PubMed1989

Chromosomal localization of zinc finger protein genes in man and mouse.

We have determined the mouse and human chromosomal location of a gene (Zfp-3) that codes for a protein that contains potential DNA zinc-binding fingers. An analysis of the segregation of restriction fragment length polymorphisms in recombinant inbred strains and in an interspecific backcross demonstrated that Zfp-3 is located on mouse chromosome 11. Zfp-3 is very closely linked to the Trp53-1 locus but unlinked to another finger protein gene Zfp-4 located on mouse chromosome 8. In humans ZFP3 has been localized to chromosome 17p12-17pter and thus is part of the conserved linkage group between this chromosome and the distal half of mouse chromosome 11.

Animals↗
PubMed1989

Is early natural menopause a biologic marker of health and aging?

The relation between age at natural menopause and all-cause mortality was investigated in a sample of 5,287 White women, ages 55 to 100 years, naturally-postmenopausal, Seventh-day Adventists who had completed mailed questionnaires in 1976. The age-adjusted odds ratio of death during 1976-82 in women with natural menopause before age 40 was 1.95 (95% confidence interval = 1.24, 3.07), compared to the reference group of women reporting natural menopause at ages 50 to 54. Corresponding odds ratios of death were 1.39 (95% CI = 1.06, 1.81) for natural menopause at ages 40 to 44, and 1.03 (95% CI = 0.84, 1.25) for natural menopause at ages 45 to 49. Among 3,166 White, 55- to 100-year-old, surgically-postmenopausal, Adventist women, there was no relation between age at surgical menopause and mortality. Logistic regression analyses indicated that findings from this study were apparently not due to confounding by smoking, over- or underweight, reproductive history, or replacement estrogen use.

Adult↗
PubMed1988

The Camberwell Collaborative Depression Study. I. Depressed probands: adversity and the form of depression.

The Camberwell Collaborative Depression Study is an investigation of a series of 130 patients (76 female; 54 male) attending the Maudsley Hospital Services with unipolar depression of recent onset (the probands), and of their first-degree relatives. This paper describes the first element of the study, the investigation of the index cases or probands, which was carried out by members of the MRC Social Psychiatry Unit over the period 1982-1985. A description of the methods of the study is followed by an analysis of life events in relation to the symptomatic pattern of the depressive state. An 'endogenous' group was defined as cases of depression falling within Catego classes D and R, and compared with a 'neurotic' group conforming to classes N and A. The hypothesis that the 'endogenous' group of disorders would be relatively independent of prior life stress was not confirmed. Depressed women were more likely to have experienced life events or difficulties than their male counterparts, and there was some evidence that sex, but not age or social class, influenced the relationship between adversity and the type of depression. Examination of the timing of life events was strongly suggestive of a causal effect, with a pronounced rise in the month before onset. This was not limited to the most severe events. Differences between the 'endogenous' and 'neurotic' groups in the temporal patterning of events before onset are discussed. The findings are interpreted in terms of the literature on the topic.

Adult↗
PubMed1987

Alterations in neutrophil superoxide production following piroxicam therapy in patients with rheumatoid arthritis.

Twenty patients with classical rheumatoid arthritis were enrolled in a study to determine the effects of piroxicam therapy on neutrophil function as defined by chemotaxis and superoxide anion (O2-) production. T-lymphocyte chemotaxis was also evaluated in these patients. Leukocytes were obtained from these subjects initially, after two weeks of placebo treatment, and subsequently after four and 10 weeks of piroxicam therapy (20 mg, once daily). Responses were compared to simultaneously tested normal controls and to the patient's own cells obtained at the different time points. Studies showed that four and 10 weeks of piroxicam therapy resulted in significantly suppressed neutrophil O2- production in response to phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). O2- production in response to opsonized zymosan was not significantly affected after four weeks of therapy, but was significantly reduced after 10 weeks of therapy when compared to the patient's own cell response after two weeks of placebo treatment. Unlike O2- production, PMN random migration and chemotaxis in response to C5a or FMLP did not differ significantly from normal or untreated patient controls. Analysis of T-lymphocyte migration showed that T-cell random migration or migration to the chemokinetic agent, casein, was not significantly altered by piroxicam therapy. However, when T lymphocytes were tested for chemotaxis in response to lymphocyte-derived chemotactic factor for T cells (LCF), T cell migration was significantly suppressed after 10 weeks of therapy. Furthermore, when T cells from these subjects were cultured for 24 h, random migration was significantly reduced after four and 10 weeks of piroxicam therapy when compared to the patient prior to therapy, and migration in response to LCF was suppressed after four weeks of therapy when compared to normal controls. These data indicate that in patients with rheumatoid arthritis, treatment with piroxicam will significantly suppress PMN O2- production and may also alter the locomotor capacity of T lymphocytes. These actions may contribute to the antiinflammatory effects of piroxicam.

Adult↗
PubMed1987

Social networks, social support and the type of depressive illness.

We hypothesised that there would be greater deficiencies in the quality and quantity of close personal relationship and social support in "neurotic" than in "endogenous" depressives, and that the relation between support and recovery would be stronger in the former. One hundred and thirty men and women who contacted hospital psychiatric services with depression were interviewed, and 119 (92%) reinterviewed after approximately 4 months. The association between the type of depression and deficiencies in social relationship was not impressive. However, differences were apparent in the prognostic implications of social relationship. For "neurotic" depressives, about half the social support variables assessed were significantly related to outcome, whereas the only significant predictor for "endogenous" cases was the presence of a close confidant. The results argue for further research on social support in clinical samples of acute depression.

Adaptation, Psychological↗