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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 703 records · Page 39Linked to original sources

Mismatch repair and recombination in E. coli.

The involvement of the E. coli methyl-directed and very short patch (vsp) mismatch repair systems in bacteriophage lambda recombination has been studied. Genetic crosses and heteroduplex transfection experiments were performed using lambda phages with sequenced mutations in the cl gene. The results indicate that methyl-directed repair does operate during bacteriophage lambda recombination but generally does not contribute to the formation of recombinants involving close markers. Vsp repair apparently acts during bacteriophage lambda recombination to produce recombinants involving close markers because its action does not involve extensive excision tracts. Marker-specific hyperrecombination and the apparent clustering of genetic exchanges in bacteriophage lambda recombination can be accounted for by the action of the vsp repair system.

Bacteriophage lambda↗

Amino acid transport in membrane vesicles from CHO-K1 and alanine-resistant transport mutants.

Membrane vesicles were prepared from CHO-K1 and alanine-resistant transport mutants, alar4 and alar4-H3.9. Alar4 is a constitutive mutant of the A system, and alar4-H3.9, derived from alar4, may be the result of amplification of a gene coding for an A-system transporter. Under conditions in which the same membrane potential (interior negative) and Na+ gradient were employed, the mutant vesicles show increases in the A system over that of the parental CHO-K1 cell line, paralleling, but not equivalent to, that found in whole cells. L-system and 5'-nucleotidase activities of these vesicles were similar, indicating that the increased A-system activity of the mutant vesicles is not due to the differential enrichment of the A system in these vesicles. The membrane potential was produced by a K+ diffusion gradient (internal greater than external) in the presence of valinomycin or by the addition of a Na+ salt of a highly permeant anion such as SCN-. Monensin was employed to study the effect of the Na+ gradient on transport and membrane potential. The latter was determined by measuring the uptake of tetraphenylphosphonium ion. A negative membrane potential determines the concentrative ability and the initial velocity of the A system in these vesicles. The concentration of external Na+ has a stimulatory effect on the initial velocity of this system. However, the Na+ gradient (external greater than internal) has no effect on the initial velocity or the membrane potential when the potential is set by valinomycin and high internal K+. Little if any ASC system could be detected in vesicles from CHO-K1.

Alanine↗

Mismatch repair of deaminated 5-methyl-cytosine.

Deamination of 5-methyl-cytosine in double-stranded DNA produces a G-T mismatch. Heteroduplexes of bacteriophage lambda DNA containing a G-T mismatch at the site of a G-5-meC base-pair in one of the parental phages were constructed and used to transfect Escherichia coli cells. Genetic analysis of the progeny phages derived from such heteroduplexes suggests that, in E. coli, mismatches resulting from the deamination of 5-methyl-cytosine are repaired by a system requiring the E. coli dcm methylase and some, but not all, of the functions of the E. coli methyl-directed mismatch repair system. The repair appears to act only on the G-T mismatch and acts specifically to restore the cytosine methylation sequence.

5-Methylcytosine↗

Animal model of acute pericarditis and its progression to pericardial fibrosis and adhesions: ultrastructural studies.

To study the evolution of pericardial inflammation, we have developed a model of pericarditis in sheep by surgically injecting heat-killed staphylococci and Freund's adjuvant into the pericardial cavity under sterile conditions. The pericarditis evolved through the following phases: 1) inflammatory response, 2) mesothelial cell injury and desquamation, and 3) fibrotic phase. At 3-24 hr there was increased microvascular permeability, which resulted in the exudation of fluid, neutrophils, macrophages, and fibrin into the pericardial cavity and the pericardial interstitium. By 72 hr, large numbers of inflammatory cells were aggregated on the mesothelial surfaces and dispersed throughout the pericardial cavity, either as free-floating cells or located between strands of fibrin. At 6 days, fibrinolysis was apparent along the mesothelial surfaces; and newly formed collagen fibrils were deposited throughout the interstitial spaces and among the aggregated cells. These fibrils provided a matrix for the growth of new blood and lymphatic vessels into new connective tissue on both parietal and visceral pericardial surfaces. At 2 weeks, intrapericardial fibrosis had produced focal adhesions between the pericardial surfaces. At 1 month, extensive areas of the pericardial cavity were obliterated. By 9 months, there was a marked reduction in the numbers of cells and blood vessels and increased deposition of collagen and elastic fibers. The intrapericardial injection of heat-killed staphylococci and adjuvant provides a reproducible animal model to study the time course of pericardial inflammation.

Acute Disease↗

A randomized trial of two types of adjuvant chemotherapy in radiotherapy-treated patients with clinical stages I and II high-grade non-Hodgkin's lymphoma.

This paper reports the 8-year results of comparing the use of two types of adjuvant chemotherapy following involved field radiotherapy for clinical stages I and II high-grade non-Hodgkin's lymphoma. Twenty-four patients received 6 weeks of VAP plus 2 years of oral maintenance chemotherapy, and 30 had six cycles of CMOPP. Four patients were not in complete remission at completion of i.v. chemotherapy (CR rate 91%). Ten patients (18.5%) have relapsed (VAP/M = 5; CMOPP = 5), with only two of these remaining alive, both of them being disease free. There have been three deaths from intercurrent causes, one from malignant melanoma and the other two from myocardial infarction. The relapse-free survivals at 2, 5 and 8 years were 80%, 76% & 76% respectively. The overall survivals at the same time points were 86%, 72% & 68%. There were no significant differences in either relapse-free or overall survival for either of the two treatment groups. The shorter period of weekly intravenous chemotherapy (VAP/M) was better tolerated than 36 weeks of CMOPP, and the former appears to produce equivalent results.

Adolescent↗

Behavioral interactions of ethanol and methylxanthines.

The effect of the methylxanthines caffeine, theophylline and isobutylmethylxanthine (IBMX) on ethanol-induced ataxia and loss of righting reflex was investigated in three strains of mice. A significant potentiation of ethanol-induced ataxia was produced in all strains of mice at 20, 45 and 75 min after ethanol in mice pretreated with 62.5 mg/kg caffeine and 12.5 mg/kg IBMX. In mice pretreated with 40 mg/kg caffeine potentiation of ethanol-induced ataxia was observed only at 20 min after ethanol. Theophylline pretreatment produced no alteration in ethanol-induced ataxia. The results of methylxanthine pretreatment on ethanol-induced ataxia were similar, regardless of a shorter (10 min) or longer (75 min) pretreatment time. The methylxanthines produced no effect on motor coordination or behavior when administered separately. Although ethanol-induced loss of righting reflex was shortened by theophylline, neither caffeine nor IBMX altered the duration of loss of righting reflex. It is possible that inhibition of adenosine uptake, a known effect of the methylxanthines, may be a more likely explanation for the modulation of the behavioral effects of ethanol.

1-Methyl-3-isobutylxanthine↗

Contributions of in vitro fertilization to knowledge of the reproductive endocrinology of the menstrual cycle.

The administration of ovarian stimulants to endocrine-normal women in IVF programmes gives the clinical endocrinologist an opportunity to modify natural folliculogenesis. Use of antioestrogens and/or gonadotrophins at the correct time has demonstrated that follicular atresia can be prevented and that multiple pregnancy-potent haploid ova can be obtained. Scrutiny of spontaneous menstrual cycles in patients who show unsatisfactory IVF responses has identified two new syndromes, premature follicle selection and occult ovarian failure, in these patients. The incidence of these disorders in fertile women is still unclear. Early results suggest that endocrine manipulations may overcome premature follicle selection and induce codominant folliculogenesis. Inhibin is a recently characterized ovarian protein which is increased in peripheral blood during IVF treatment. Results from IVF cycles suggest that plasma inhibin may be a new index of follicular function. Other potential indices of ovarian function, such as the luteal protein relaxin, may also develop from the application of basic research to IVF and advance knowledge of the human ovarian and menstrual cycles.

Estradiol↗

Control of A-system amino acid transport by a second regulatory gene R2 in Chinese hamster ovary cells CHO-K1 and the possible connection of this gene with insulin activity.

Evidence based on a study of alanine-resistant (Alar), constitutive mutants of CHO-K1 cells and the conditions that favor stimulation of the A system of amino acid activity supports the model that the A system of amino acid transport in these cells is repressible and under negative control of regulatory gene R1. In this study, we show that mutant Alar6, when grown under conditions of repression, has an A system of amino acid transport activity similar to that of the derepressed parental cell line, CHO-K1 (wild type) and of the fully constitutive mutant in gene R1, Alar4. However, the A system of Alar6 is further derepressible. The Vmax for proline transport through this system in mutant Alar6 is four times that of the parental culture, with no significant change in Km. Analysis of hybrids produced by crossing mutant Alar6 with the parental culture and with Alar4 shows that mutant Alar6 is recessive to wild type and complements mutant Alar4. Although the amino acid transport A system of CHO-K1 is stimulated by insulin, mutant alar6 is not stimulated by insulin. These results support the hypothesis that mutant alar6 results from mutation in another regulatory gene, R2, that, in conjunction with gene R1, negatively controls the expression of a structural gene for the A-system transport. Evidence also indicates that R2 gene product is not responsive to amino acids and that insulin stimulation of the A system may result from insulin inactivation of this repressor.

Amino Acids↗

Repair of a mismatch is influenced by the base composition of the surrounding nucleotide sequence.

Heteroduplexes with single base pair mismatches of known sequence were prepared by annealing separated strands of bacteriophage lambda DNA and used to transfect Escherichia coli. A series of transition (G:T and A:C) and transversion (G:A and C:T) mismatches located throughout most of the bacteriophage lambda cI gene has been examined. The results suggest that the transition mismatches are generally better repaired than the transversion mismatches and that, at least for the transversion mismatches studied, repair efficiency increases with increasing G:C content in the neighboring nucleotide sequence. This specificity of the E. coli mismatch repair system can account, in part, for the similar frequencies of base substitution mutations throughout the E. coli genome.

Bacteriophage lambda↗

Coping as an index of illness behavior in panic disorder.

Illness behavior in panic disorder was examined by comparing the coping strategies of female primary care patients (34 with panic disorder, 30 with simple panic, and 78 without panic.) Relationships of coping and distress were also examined within each group. The groups differed significantly on the Ways of Coping Checklist, anxiety (SCL-90 and Zung scales), depression (SCL-90 and Beck scales), and number of phobias. The panic disorder group used proportionately less problem-focused and more wishful thinking than the other groups. Within the panic disorder group, anxiety and depression were correlated negatively with problem-focused coping and positively with wishful thinking, and number of phobias was correlated negatively with the seeking of social support and positively with wishful thinking. Most importantly, when an attempt was made to statistically separate panic patients with multiple phobias from those without multiple phobias, coping was a better marker than was distress. These results emphasize the importance of cognitions in illness behavior and anxiety disorder.

Adaptation, Psychological↗

Does colchicine work? The results of the first controlled study in acute gout.

We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients.

Acute Disease↗