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Biomedical subjects

P Jackson

Publications and source records attributed to P Jackson.

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

Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy.

Helicobacter pylori causes chronic (type B) gastritis. The 'intestinal' form of gastric cancer arises against a background of chronic gastritis, and prospective epidemiological studies have shown that H pylori is a major risk factor for this. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging where there is chronic epithelial cell injury associated with H pylori gastritis. In vitro bromodeoxyuridine labelling of endoscopic antral biopsy specimens was used to measure mucosal cell proliferation in H pylori associated gastritis before and after therapy for H pylori triple infection. Cell proliferation was increased in H pylori associated gastritis patients compared with normal controls and patients with H pylori negative chronic gastritis (p = 0.0001; Tukey's Studentised range). There was no difference in antral epithelial cell proliferation between duodenal ulcer and non-ulcer subjects infected with H pylori (p = 0.62; Student's t test). Antral mucosal cell proliferation fell four weeks after completing triple therapy, irrespective of whether or not H pylori had been eradicated (p = 0.0001). At retesting six to 18 months later (mean = 12 months), however, those in whom H pylori had not been successfully eradicated showed increased mucosal proliferation compared with both H pylori negative subjects at a similar follow up interval and all cases (whether H pylori positive or negative) four weeks after completion of triple therapy (p = 0.024). These findings suggest that H pylori infection causes increased gastric cell proliferation and in this way may play a part in gastric carcinogenesis.

Adult↗
PubMed1995

Cell proliferation in the gastric corpus in Helicobacter pylori associated gastritis and after gastric resection.

Patients who have undergone gastric resection are at higher risk of developing gastric carcinoma than normal subjects, and bile reflux is believed to play a role in carcinogenesis. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. Helicobacter pylori is considered a major risk factor for gastric cancer in the intact stomach. It has been shown previously that antral cell proliferation is increased in H pylori gastritis and falls to normal levels after eradication of the organism. Little is known of corpus cell proliferation in H pylori gastritis or after gastric resection. Using in vitro bromodeoxyuridine labelling of endoscopic biopsy specimens we have found that corpus cell proliferation is increased in H pylori gastritis. Cell proliferation was greater in corpus biopsy specimens of resected stomachs than in H pylori gastritis. Subgroup analysis of patients who had undergone gastric resection indicated that those positive for H pylori had higher levels of cell proliferation than those negative for the organism. These findings provide further evidence that H pylori and bile have a role in gastric carcinogenesis and suggest that their presence has a synergistic effect on gastric epithelial cell proliferation.

Adult↗
PubMed1995

Lymphocytic gastritis and associated small bowel disease: a diffuse lymphocytic gastroenteropathy?

AIM: To investigate the natural history of lymphocytic gastritis (LG) and its relation to Helicobacter pylori infection and to coeliac disease using serology, duodenal biopsy and a small intestinal permeability test. METHOD: Twenty two patients diagnosed as having LG between 1984 and 1994 were investigated by upper gastrointestinal endoscopy at which gastric and duodenal biopsy specimens were taken for histological assessment and immunohistology. Serum was collected for measurement of anti-H pylori, anti-gliadin and anti-endomysial antibodies. A lactulose/mannitol absorption test was performed within one week of endoscopy. Control groups were studied by histology, serology and permeability tests. RESULTS: Three patients had been recently diagnosed as having LG while 15 still had the condition after a mean of 13.9 (range two to 38) months. LG involved the antrum alone in three patients, antrum and body in seven, body alone in six, and gastric remnant in two. Gastroduodenal intraepithelial lymphocytes (IELs) were T cells and predominantly of T suppressor (CD8) type. Duodenal IELs were increased compared to age/sex matched controls with chronic gastritis. Four patients had duodenal villous atrophy. Four patients no longer had LG after a mean of 29.3 (10-70) months but had increased gastroduodenal IELs. H pylori was present in four (22%) of 18 patients with LG but H pylori serology was positive in 11 (61%) of 18. There was no difference in seropositivity when compared with age/sex matched controls with dyspepsia. Eleven of 20 patients with LG tested had abnormal lactulose/mannitol absorption (v none of 22 controls with chronic gastritis). Four patients with LG, all with villous atrophy, were seropositive for IgA endomysial antibody. CONCLUSIONS: The persistence of LG with time, the association with increased duodenal IELs and abnormal small intestinal permeability suggests LG may be a manifestation of a diffuse lymphocytic gastroenteropathy related to sensitivity to gluten or some other agent.

Adult↗
PubMed1995

p53-dependent activation of the mouse MCK gene promoter: identification of a novel p53-responsive sequence and evidence for cooperation between distinct p53 binding sites.

Transcriptional activation by p53 is dependent on the presence of a specific p53 binding site within control sequences of the target gene. One such target gene is the mouse muscle-specific creatine kinase (MCK) gene, which contains a p53 binding site between promoter residues -3182 and -3133 relative to the transcription start site. This DNA sequence is reported to be sufficient to confer p53-dependent activation on the MCK promoter. In contrast to this finding, evidence from promoter deletion studies suggests that sequences in the MCK promoter other than this p53 binding site also permit p53-dependent activation. To investigate this possibility, we have further examined sequences in the MCK promoter required for transcriptional activation by mouse p53. We report here identification of a second p53-responsive sequence within the MCK promoter. This novel sequence is situated between residues -177 and -81, and can confer p53-dependent, position- and orientation-independent activation on a heterologous promoter. Moreover, this sequence can specifically bind mouse and human p53. By promoter deletion studies, we provide evidence that these two elements cooperate to provide high-level, p53-dependent activation of the MCK promoter.

Animals↗
PubMed1995

Relationships between nutrient intake and progression/regression of coronary atherosclerosis as assessed by serial quantitative angiography.

To elucidate the direction and magnitude of effects of nutrition on coronary artery disease (CAD), the relation between nutrient intake and angiographic changes were examined in the course of a controlled dietary trial. Ninety men with symptomatic CAD and serum cholesterol greater than 232 mg/dL were entered into a randomized controlled trial of a lipid-lowering diet, or of diet plus cholestyramine, compared with usual cardiac care. Of those in the first and second groups, 50 patients completed the trial and are the subject of this report. Quantitative coronary angiography was performed at baseline and at 39 months. From repeated dietary assessment during the trial, mean nutrient intakes were computed, and their relationships with change of coronary artery narrowing were analyzed. Progression of coronary disease was directly, strongly and independently associated with intake of saturated fatty acids of chain length 14-18. This was not fully explained by the effects of saturated fat in raising serum cholesterol; after adjustment for low density lipoprotein cholesterol level, stearic acid (C18:0) intake remained independently predictive of progression. No 'protective' effect of linoleic, linolenic or eicosapentaenoic acid was demonstrable. Intake of trans fatty acids was directly related to progression. Together with the favourable treatment effects on angiographic appearance and clinical end-points, these findings provide further support for a causal role of saturated fats in CAD; restriction of foods containing such fats should be emphasized as part of regimens aimed to reduce progression of coronary atherosclerosis.

Adult↗
PubMed1995

Effect of hemodialysis on total antioxidant capacity and serum antioxidants in patients with chronic renal failure.

Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis for chronic renal failure. Increased lipid peroxidation and depletion of chain-breaking antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of a single episode of hemodialysis on antioxidant status in 22 patients and control subjects. Overall, total antioxidant capacity of serum was increased in dialysis patients, but there was a marked reduction after hemodialysis [571 +/- 31 vs 342 +/- 22 mumol/L Trolox (water-soluble vitamin E analog) equivalents, P < 0.001]. The increase in total antioxidant capacity before hemodialysis was almost entirely due to relatively high serum urate. Among individual chain-breaking antioxidants, dialysis led to a decrease in urate (398 +/- 15 vs 136 +/- 12 mumol/L, P < 0.001), ascorbate (10.5 +/- 1.7 vs 5.9 +/- 1.0 mumol/L, P < 0.01), and lipid-corrected tocopherol (4.70 +/- 0.56 vs 4.26 +/- 0.39 mumol/mmol cholesterol, P < 0.05). Protein thiol groups increased after dialysis (328 +/- 16 vs 422 +/- 22 mumol/L, P < 0.001), whereas albumin remained unchanged (40.1 +/- 1.1 vs 41.0 +/- 1.6 g/L, not significant). Although total antioxidant capacity of serum is increased in hemodialysis patients, depletion of key chain-breaking antioxidants may lead to accelerated atherogenesis.

Adult↗
PubMed1994

Transcriptional regulation of the PCNA promoter by p53.

We have examined the ability of p53 to affect transcription from the PCNA promoter in a number of cell types. In HeLa cells, p53 activates the PCNA promoter whereas in CV1, CHO, L929, and Saos-2 cells the same promoter is strongly repressed. By using stepwise deletions of the PCNA promoter, we have identified two potential regions of the promoter which are important for the ability of p53 to activate transcription in HeLa cells.

Animals↗
PubMed1994

A V lambda x-bearing monoclonal antibody with similar specificity and sequence to encephalitogenic T cell receptors.

The fine specificity of mAb F28C4 to myelin basic protein (MBP), acetyl residues 1-9, has been compared with the previously described specificity of an encephalitogenic T cell clone, PJR-25. F28C4 has been found to express a cross-reactive idiotope (CRI) that is shared with MBP acetyl peptide 1-9-specific TCR. The CRI seems to be located at or near the Ag-combining site of F28C4 and the TCR and, thus, might possibly result from overlapping epitope specificity. We tested the fine epitope specificity of F28C4 by using alanine-substituted peptide analogues and found that residues critical for TCR recognition, Cln3 and Pro6, are also necessary for F28C4 recognition. By using nuclear magnetic resonance, we found that the MBP acetyl peptide 1-9 binds F28C4 in an extended conformation and that the central residues are more tightly bound than the terminal residues, much like the MBP-TCR interaction. Furthermore, sequence homology (75% overall) was found between the regions that contained CDR3 of F28C4 VL and VH and the VDJ junction of the TCR V beta. This homology is not shared by other Ig CDR3 regions and arises, in part, because F28C4 uses an unusual V lambda light chain, V lambda x. Thus, F28C4 shares a CRI with the TCRs, possibly as a result of having similar fine epitope specificity and sequence homology. The anti-CRI mAb can down-modulate experimental allergic encephalomyelitis; thus, it is possible that Abs that are similar to F28C4 may play an important immunoregulatory role in experimental allergic encephalomyelitis in vivo.

Amino Acid Sequence↗
PubMed1994

Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice.

Mutants and fusion products of the c-abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre-B-lymphoma induction in pristane-treated N-myc transgenic BALB/c mice. A-MuLV induced PCs in 21 of 25 mice with a mean post-pristane latency period of 46 +/- 9 days, compared to 134 +/- 25 days in controls exposed to pristane alone. delta XB, a mutant of type IV c-abl with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 +/- 7 days, indicating that gag sequences are not required for rapid PC induction. The delta XB delta Nar mutant that carried a large C-terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C-terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR-ABL fusion constructs encoding an 185-kDa protein as in acute leukemia, or a 210-kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane-induced PC development in the N-myc transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non-transgenic littermates developed a pre-B lymphoma after A-MuLV infection, and none of 10 normal littermates infected with delta XB virus developed a construct-carrying tumor. This result suggests that PC acceleration is due to co-operative interaction of the N-myc transgene and activated abl. Infection of N-myc transgenic bone marrow or spleen cells with A-MuLV in vitro led to the outgrowth of pre-B lymphomas after transplantation to pristane-treated BALB/c recipients. The lymphoma-inducing activity of A-MuLV depends on its high titer, since diluted A-MuLV or the lower-titered delta XB induced only PCs under the same conditions. The v-abl, delta XB and BCR-ABL-carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N-myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.

Animals↗
PubMed1994

Microwave antigen retrieval of beta-amyloid precursor protein immunoreactivity.

Formalin fixation reduces beta-amyloid precursor protein (beta APP) immunoreactivity which restricts its study in archival tissue. Formic acid pretreatment has previously been used in an attempt to overcome this problem, but makes the sections very friable. In the present study, a microwave antigen retrieval method has been compared with formic acid pretreatment for retrieving beta APP immunoreactivity in formalin-fixed, paraffin-embedded human brain tissue. Microwave treatment resulted in superior retrieval of beta APP antigenicity in dystrophic neurites in Alzheimer's disease and in injured axons after head injury, using antibodies to three different epitopes. Unlike formic acid, microwave treatment causes minimal adverse effects on the strength and slide adhesion of the sections.

Alzheimer Disease↗
PubMed1994

Nutrient intake and progression of coronary artery disease.

The relation between nutrient intake and progression of coronary artery disease was examined in 50 men receiving a lipid-lowering diet or usual care in the St. Thomas' Atherosclerosis Regression Study. Nutrient intake was assessed by diet history. Changes in coronary angiograms were measured by quantitative image analysis. In univariate linear regression analysis progression of disease over 39 months, as measured by decrease in minimum absolute width of coronary segments, was directly related to dietary energy (p < 0.001) and to the absolute intakes of total fat (p < 0.001), saturated fat (p < 0.001), monounsaturated fat (p = 0.016) and cholesterol (p = 0.06). No significant associations were seen with polyunsaturated fat, carbohydrate, protein, fiber, alcohol or with the ratio of intakes of polyunsaturated fatty acids to saturated fatty acids. In multiple linear regression analysis the associations of change in minimum absolute width of coronary segments with total or saturated fat persisted when adjusted for plasma low-density lipoprotein cholesterol concentration, age, weight, blood pressure, smoking or treatment group assignment. The findings suggest that in middle-aged men, progression of CAD is strongly influenced by intake of saturated fatty acids, an effect mediated in part by mechanisms other than the influence of this nutrient on plasma cholesterol and low-density lipoprotein cholesterol.

Basal Metabolism↗
PubMed1994

The analysis of fluorophore-labeled glycans by high-resolution polyacrylamide gel electrophoresis.

Many important biological processes are mediated by the carbohydrate moieties of glycoconjugates. Their structural determination presents considerable difficulties because of both their complex structures and the small quantities which are available from biological sources. In order to address some of the problems in this field a new method of glycan analysis has been developed in which saccharides having a reducing end group are labeled covalently with a fluorophore and the derivatives separated with high resolution by polyacrylamide gel electrophoresis. Fluorophores have been used that enable the electrophoretic separation of positional isomers, anomers, and epimers of a variety of saccharides. Mixtures of complex glycans obtained by enzymatic cleavage from glycoproteins yield electrofluorograms showing high-resolution oligosaccharide profiles. Techniques for obtaining saccharide sequence information from isolated oligosaccharides have been developed. Subpicomolar quantities of individual saccharides can be detected using an imaging system based on a cooled charge-coupled device. The method enables rapid, simultaneous, parallel analyses of multiple samples. The analytical and clinical applications and potential of the system are discussed.

Carbohydrate Sequence↗
PubMed1994

The use of polyacrylamide gel electrophoresis for the analysis of acidic glycans labeled with the fluorophore 2-aminoacridone.

A method is described for the electrophoretic analysis of fluorophore-labeled acidic glycans. Various glycoproteins were treated with the enzyme, peptide N-glycosidase F, to release mixtures of asparagine-linked glycans that were then labeled with the fluorophore 2-aminoacridone, and the resulting derivatives electrophoresed in high-density polyacrylamide gels. The acidic glycans were separated with high resolution and distinct, well-resolved fluorescent band patterns were produced. Neutral saccharides did not electrophorese in the system. Information on the structure of the glycans was revealed by the changes in the band patterns observed after the mixtures of the glycan fluorophore derivatives were treated with either of the enzymes neuraminidase or beta-galactosidase. Quantities of glycoprotein as little as 10 micrograms were analysed without difficulty. The electrofluorograms were viewed using a digital imaging system based on a cooled charge-coupled device. The method was also demonstrated using purified acidic glycans of known structure. The method was easy to use, enabled the sensitive analysis of multiple samples in parallel and should be a useful addition to the range of glycan analytical techniques.

Acids↗
PubMed1994

Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale).

The dried rhizomes of Indonesian ginger, Zingiber officinale, were investigated for antirhinoviral activity in the plaque reduction test. Fractionation by solvent extraction, solvent partition, and repeated chromatography guided by bioassay, allowed the isolation of several sesquiterpenes with antirhinoviral activity. The most active of these was beta-sesquiphellandrene [2] with an IC50 of 0.44 microM vs. rhinovirus IB in vitro.

Antiviral Agents↗
PubMed1994

Management of the uncomplicated pregnant diabetic client in the ambulatory setting.

This article discusses health care provider management of the uncomplicated pregnant diabetic client in the ambulatory setting. The primary care management process includes combining knowledge about the individual with knowledge of the disease process of diabetes in order to identify problems. Through a sharing of knowledge and information and a team approach, health care providers and their clients work together to develop and implement a logical sequence of safe, comprehensive care. The purpose of this article is to provide information on health care management of uncomplicated diabetes in pregnancy in the ambulatory setting. Topics include classifications of diabetes, normal insulin metabolism and insulin metabolism during pregnancy, implications of diabetes for the mother and fetus, preconception management and risk factor identification, screening and diagnostic tests, and management. Management includes baseline assessment, blood glucose monitoring, nutrition, exercise and insulin therapy as well as fetal surveillance and postpartum follow-up.

Blood Glucose Self-Monitoring↗
PubMed1994

Intensive care management of multiple-organ dysfunction due to falciparum malaria in a married couple.

A married couple presented simultaneously with malignant tertian malaria and rapidly developed septicaemia and severe multiple-system organ failure. Despite schizonticidal treatment and multisystem support in intensive care the husband died. The selection of chemoprophylactic agents for this couple was not ideal and the duration of therapy before exposure to risk was inadequate. Severe infection with plasmodium falciparum is life-threatening and requires early diagnosis. It is best managed in an intensive care unit where continuous assessment may enable rapid detection of clinical deterioration and allow appropriate treatment to be instituted. The diagnosis should be considered in symptomatic patients who have travelled through areas where malaria is endemic. Recognised guidelines for the prescription of malarial chemoprophylaxis should be followed to ensure adequate protection.

Critical Care↗