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Biomedical subjects

P Jones

Publications and source records attributed to P Jones.

At least 289 records · Page 16Linked to original sources
PubMed1993

Cloning and characterization of an ftsZ homologue from a bacterial symbiont of Drosophila melanogaster.

A 1194 bp open reading frame that codes for a 398 amino acid peptide was cloned from a lambda gt11 library of Drosophila melanogaster genomic DNA. The predicted peptide sequence is very similar to three previously characterized protein sequences that are encoded by the ftsZ genes in Escherichia coli, Bacillus subtilis and Rhizobium meliloti. The FtsZ protein has a major role in the initiation of cell division in prokaryotic cells. Using a tetracycline treatment that eradicates bacterial parasites from insects, the ftsZ homologue has been found to be derived from a bacterium that lives within the D. melanogaster strain. However, polymerase chain reaction (PCR) amplification of the gene from treated embryos suggests that it is not derived from a gut bacterium. Nevertheless, by amplifying and characterizing part of the 16S rRNA from this bacterium we have been able to demonstrate that it is a member of the genus Wolbachia, a parasitic organism that infects, and disturbs the sexual cycle of various strains of Drosophila simulans. We suggest that this ftsZ homologue is implicated in the cell division of Wolbachia, an organism that fails to grow outside the host organism. Sequence and alignment analysis of this ftsZ homologue show the presence of a potential GTP-binding motif indicating that it may function as a GTPase. The consequences of this function particularly with respect to its role in cell division are discussed.

Amino Acid Sequence↗
PubMed1993

Effect of protease inhibitors and clenbuterol on the in vitro degradation of dystrophin by endogenous proteases in human skeletal muscle.

The in vitro degradation of dystrophin protein by endogenous proteases in human skeletal muscle has been investigated using a tissue homogenate assay system with subsequent protein analysis via SDS polyacrylamide electrophoresis and immunoblotting (using a monoclonal antibody to the central rod region of dystrophin). The rate of dystrophin degradation and nature of the proteolytic fragments formed at pH 5.5 and pH 7.5 (corresponding to the two major protease groups of relevance to intracellular protein catabolism) were broadly similar; incorporation of protease inhibitors in the above system suggested that Ca2+ activated proteinase and cathepsin D are principally responsible for the degradation of dystrophin at pH 7.5 and pH 5.5 respectively. The rate of dystrophin degradation at pH 7.5 was reduced by approximately 20% in the presence of 10(-5) M clenbuterol, a beta-adrenoceptor agonist with therapeutic potential in the treatment of human muscle wasting diseases.

Cathepsin D↗
PubMed1993

Early detection of protein depletion in alcoholic cirrhosis: role of body composition analysis.

BACKGROUND: Malnutrition is common in alcoholic cirrhosis. Bedside nutritional assessment techniques may be unreliable in patients with chronic liver disease. The aim of this study was to quantify changes in body composition and compare methods for measuring body composition in alcoholic cirrhosis. METHODS: Thirty-eight men with alcoholic cirrhosis were compared with 16 age-matched healthy men. Body composition was assessed using anthropometry and bioelectrical impedance to determine fat-free mass and body fat, deuterium oxide dilution to measure total body water, in vivo neutron activation analysis to measure total body protein, and dual energy x-ray absorptiometry to measure bone mineral content and total body fat mass. RESULTS: With increasing severity of cirrhosis, total body water increased, whereas total body protein decreased with a significant decrease in serum albumin levels. Total body protein levels, expressed as an index, were a more sensitive indicator of protein depletion than serum albumin levels. When patients were assessed by anthropometry and bioelectrical impedance for fat-free mass, there was no reduction compared with controls. CONCLUSIONS: Anthropometry and bioelectrical impedance do not accurately reflect changes in body composition associated with chronic liver disease. Quantification of body composition changes in alcoholic cirrhosis requires the use of direct methods such as in vivo neutron activation analysis, dual energy x-ray absorptiometry, or deuterium oxide dilution.

Adult↗
PubMed1993

Enzymatic production of optically pure (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC, lamivudine): a potent anti-HIV agent.

Although equipotent in terms of antiviral activity, the two enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) differ markedly in their cytotoxicity. (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC) is substantially less toxic than its optical antipode, and is undergoing development for the therapy of HIV infection. Cytidine deaminase from Escherichia coli is shown here to deaminate 2'-deoxy-3'-thiacytidine enantioselectively to leave 3TC essentially optically pure. This reaction has been used to develop a process for production of 3TC in multikilogram amounts. The production of cytidine deaminase was enhanced by strain improvement, fermentation development, and finally by cloning and overexpression of the gene. The enzyme was immobilized on Eupergit-C, which allowed it to be reused many times. The biotransformation conditions were optimized so that the best use could be made of the catalyst. A robust scaleable product isolation process was developed to yield the crystalline product. Overall, yields through the resolution process of 76% were obtained. All aspects of this process are capable of substantial further scaleup with only minor modifications.

Antiviral Agents↗
PubMed1993

Evidence for a Wolbachia symbiont in Drosophila melanogaster.

The bacterial cell division gene, ftsZ, was used as a specific probe to show the presence of a symbiotic bacterium in two wild type strains of Drosophila melanogaster. Under stringent hybridization conditions we have shown that the bacterium is transferred to the progeny of these strains from infected mothers and can be eradicated by treatment with the antibiotic tetracycline. We have characterized this bacterium, by amplifying and sequencing its 16S rRNA gene, as being a member of the genus Wolbachia, an organism that is known to parasitize a range of insects including Drosophila simulans. In a series of reciprocal crosses no evidence was found that the symbiont causes cytoplasmic incompatibility (CI) which is known to occur in infected strains of D. simulans. The implications of these findings are discussed.

Animals↗
PubMed1993

Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy.

OBJECTIVE: The authors determined whether microscopically positive surgical margins are detrimental to the outcome of early stage breast cancer patients treated with conservation surgery and radiation therapy. SUMMARY BACKGROUND DATA: The optimal extent of breast surgery required for patients treated with conservation surgery and radiation therapy has not been established. To achieve breast preservation with good cosmesis, it is desirable to resect as little normal tissue as possible. However, it is critical that the resection does not leave behind a tumor burden that cannot be adequately managed by moderate doses of radiation. It is not known whether microscopically positive surgical margins are detrimental to patient outcome. METHODS: The records of 259 consecutive women (262 breasts) treated with local excision (complete removal of gross tumor with a margin) and axillary dissection followed by radiation therapy for clinical stage I and II infiltrating ductal breast cancer at Duke University Medical Center and the University of North Carolina between 1983 and 1988 were reviewed. Surgical margins were considered positive if tumor extended to the inked margins; otherwise the margins were considered negative. Margins that could not be determined, either because the original pathology report did not comment on margins, or because the original specimen had not been inked were called indeterminate. RESULTS: Of the 262 tumors, 32 (12%) had positive margins, 132 (50%) had negative margins, and the remaining 98 (38%) had indeterminate margins. There were 11 (4%) local failures; 3/32 (9%) from the positive margin group, 2/132 (1.5%) from the negative margin group, and 6/98 (6%) from the indeterminate group. The actuarial local failure rates at 5 years were 10%, 2%, and 10%, respectively, p = 0.014 positive vs. negative, p = 0.08 positive vs. indeterminate (log rank test). Margin status had no impact on survival or freedom from distant metastasis; 63 patients who originally had positive or indeterminate margins were re-excised. Two of 7 with positive margins after re-excision versus 1/56 rendered margin negative had a local recurrence. CONCLUSIONS: The authors recommend re-excision for patients with positive margins because of improved local control of those rendered margin negative and identification of those patients at high risk for local failure (those who remain positive after re-excision). Because margin status impacts on local control, tumor margins after conservation surgery should be accurately determined in all patients.

Adult↗
PubMed1993

Haemophilia B Liverpool: a new British family with mild haemophilia B associated with a -6 G to A mutation in the factor IX promoter.

We report a Lancashire family with mild haemophilia B associated with a -6 G to A mutation in the factor IX promoter. This mutation has been reported previously in Britain in one other affected family. The factor IX haplotype of these two unrelated patients was determined by PCR analysis of seven polymorphic sites within or close to the factor IX gene. This analysis involved the intragenic Msp I polymorphism which we have now located precisely to allow the design of suitable PCR primers. The haplotype of both of these patients was identical suggesting but not proving a possible common origin for the mutation.

Base Sequence↗
PubMed1993

Plasma protein levels in normal human fetuses: 13 to 41 weeks' gestation.

OBJECTIVES: To establish reference ranges for the levels of alpha-fetoprotein, albumin, prealbumin (transthyretin) alpha-1-antitrypsin, transferrin, ceruloplasmin and total protein in the plasma of normal human fetuses and newborn babies. DESIGN: Prospective study of individual normal cases to fulfil objectives. SETTING: Pathology laboratories of the University of Edinburgh and the biochemistry laboratories of the University of Keele. SUBJECTS: Twenty-two normal fetuses 13 to 22 weeks of gestation and 66 babies born between 24 and 41 weeks gestation. RESULTS: Albumin is the predominant plasma protein throughout gestation. The levels of alpha-fetoprotein and prealbumin fell significantly with increasing gestation, whereas the concentrations of the other proteins studied increased. The ratios of individual proteins to total protein demonstrated similar trends. CONCLUSIONS: This study provides developmental profiles of normal human fetal plasma proteins to serve as possible reference data for abnormal fetuses. Declining levels of prealbumin (transthyretin) were unexpected and suggest a functional role for this protein in early pregnancy.

Blood Proteins↗
PubMed1993

Chloramphenicol induces the transcription of the major cold shock gene of Escherichia coli, cspA.

A downshift in temperature or exposure of cells to certain inhibitors of translation has been shown to induce the synthesis of cold shock proteins in Escherichia coli. We characterized the induction of the major cold shock protein (CS7.4, the product of the cspA gene) of E. coli in response to a shift from 37 to 15 degrees C and in response to the addition of chloramphenicol at 15 degrees C. A pulse-labeling assay and primer extension experiments indicated that the cold shock treatment resulted in a transient increase in the level of the cspA transcript and a transient induction of CS7.4, while the addition of chloramphenicol resulted in a constitutive increase in the level of cspA transcript and constitutive production of CS7.4. The addition of rifamycin immediately following the temperature downshift or along with the addition of chloramphenicol repressed the transcription of cspA as well as the induced production of CS7.4. Furthermore, changes in the cspA mRNA level were coincident with changes in CS7.4 synthesis. These results indicate that the expression of cspA induced by cold shock and chloramphenicol is at the level of transcription but not at the level of translation. Measurement of the half-life revealed that the cspA mRNA induced by chloramphenicol was more stable than that induced by cold shock.

Bacterial Proteins↗
PubMed1993

Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study.

Data from the Camberwell Collaborative Psychosis Study were used to examine the proposition that there is an excess of life events preceding the onset of psychoses of all types. Of 97 patients from the study who had episodes within the past year that were datable, 51 had developed psychotic symptoms from an essentially symptom-free state, 29 had been suffering only from neurotic symptoms, and 17 had experienced a marked exacerbation of psychotic symptoms. DSM-III diagnoses were collapsed into three major groups: 51 cases of schizophrenia; 31 cases of mania; and 14 cases of depressive psychosis. Life-event histories were taken for the six months before onset, and when these were compared with equivalent histories from a psychiatrically healthy sample from the local general population, there was a significant excess of life events, particularly in the three months before onset of psychosis. This was apparent in all groups, and remained even when events were restricted to the independent category. The excess of events began rather earlier than has been found in previous studies. In our view, this study provides some of the strongest evidence for a link between life events and the emergence of psychotic symptoms.

Adolescent↗
PubMed1993

Familial psychiatric illness and obstetric complications in early-onset affective disorder. A case-control study.

Early-onset affective disorder is associated with obstetric complications and a high familial risk of psychiatric illness, in particular psychosis. In a matched case-control study, we investigated 47 adult in-patients with major depressive disorder or bipolar 1 disorder, who had earlier in life presented to a child psychiatry department. Cases were matched on sex, social class and ethnic group with 47 controls, who were admitted to hospital for affective disorders in adult life but had no psychiatric contact before the age of 21. We found that both psychiatric disorder in first-degree relatives and a history of obstetric complications were associated with early onset. Childhood symptoms did not predict the type of adult affective disorder.

Adult↗
PubMed1993

Alpha, mu and pi class glutathione S-transferases in human synovium and cultured synovial fibroblasts: effects of interleukin-1 alpha, hydrogen peroxide and inhibition of eicosanoid synthesis.

We describe expression of alpha, mu and pi class glutathione S-transferase (GST) and, CuZn- and Mn superoxide dismutase (SOD) in human synovium and cultured synovial fibroblasts. Immunohistochemical and immunoblotting studies showed synovium and cultured cells expressed pi GST and both isoforms of SOD. Cellular localisation was largely perinuclear. No expression of alpha or mu GST was detected even though polymerase chain reaction analysis showed 4/6 subjects had positive genotypes at the polymorphic, mu class GSTM1 locus. Incubation of cultured synovial fibroblasts with H2O2, IL-1 alpha and the cyclooxygenase and lipoxygenase inhibitor, Tenidap, did not induce expression of alpha, mu or pi GST though treatment with IL-1 alpha caused a marked increase in the expression of Mn SOD.

Arthritis, Rheumatoid↗
PubMed1993

Older patients are people first.

Older people, and their health, are widely seen as 'different', writes Paula Jones. Services for older people have failed to keep pace with the medical advances which have resulted in increased longevity; they are largely ignored in the 'Health of the nation' strategy. Here she questions society's attitudes to older people and examines the consequences for the delivery of health services and for older people themselves.

Aged↗