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Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 361 records · Page 20Linked to original sources
PubMed1995

The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread.

Listeria monocytogenes secretes two distinct phospholipases C, a phosphatidylinositol-specific phospholipase C (PI-PLC) and a broad-range phospholipase C (PC-PLC). In this study, single in-frame deletion mutants with mutations in each PLC and a double mutant lacking both PLCs were characterized with regard to virulence in mice, escape from a primary vacuole, and cell-to-cell spread in cell culture. The mutant lacking PI-PLC, previously shown to be twofold less virulent than the wild type in mice, had a minor defect in escape from a primary vacuole but was not notably affected in cell-to-cell spread. The mutant lacking PC-PLC was 20-fold less virulent in mice and was defective in cell-to-cell spread but had no measurable defect in escape from a primary vacuole. The mutant lacking both PLCs was 500-fold less virulent in mice and was severely diminished in its ability to escape from the primary vacuole and to spread cell to cell. Cellular levels of diacylglycerol and ceramide, products of PLC activity, accumulated beginning 3 to 4 h after infection of cells with wild-type bacteria. The bacterial PLCs were partially responsible for this activity, since cells infected with the mutant lacking both PLCs had a reduced increase in diacylglycerol and no increase in ceramide. Elevation of diacylglycerol in the absence of bacterial PLCs indicated that host cell phospholipase(s) was activated during infection. The results of this study were consistent with the two bacterial PLCs having overlapping functions throughout the course of intracellular infection. Furthermore, the PC-PLC, and possibly PI-PLC, appeared to be enzymatically active intracellularly.

Animals↗
PubMed1995

Identifying deprived areas using indices from the 1991 census and information about the recipients of community charge and council tax benefit.

STUDY OBJECTIVE: To assess the level of agreement between those small areas selected as materially deprived by indicators derived from the 1991 census and those indicators derived from local authority benefit data. DESIGN: Census indices of deprivation and local authority benefits data were collected, compiled, and correlated for three districts in Yorkshire at enumeration district (ED) level. The composition of the "most deprived" quintiles of pairs of indicators was compared. PARTICIPANTS: Data were obtained from the 1991 census for the Bradford, Kirklees, and Rotherham districts. Community charge benefit and council tax benefit data were also obtained for all claimants in the three districts. MAIN RESULTS: Correlation coefficients between indicators of deprivation from the census and from the benefits data were shown to be quite high. However, the composition of EDs in the highest quintiles of pairs of indicators showed marked differences. CONCLUSIONS: Census indicators of deprivation and local authority benefits data select broadly similar groups of "deprived" EDs. Where deprivation indicators disagree is in the composition of specific quintiles which is due partly to methodological differences in the construction of the indicators, partly to deficiencies of the benefit data, and partly to the different aspects of deprivation which the various indicators measure.

Data Collection↗
PubMed1995

Adaptations in muscle metabolism to prolonged voluntary exercise and training.

In previous research we established using a short-term (5-7 days) training model that increases in muscle oxidative potential are not a prerequisite for the characteristic energy metabolic adaptations (lower lactate, glycogen depletion, and phosphocreatine hydrolysis) observed during prolonged exercise. To investigate whether increased muscle aerobic potential further potentiates the metabolic adaptive response, seven healthy male volunteers [maximal O2 uptake (VO2max) = 45.1 +/- 1.1 (SE) ml.kg-1.min-1] engaged in an 8-wk training program consisting of 2 h of cycle exercise at 62% of pretraining VO2max 5-6 times/wk. Analysis of tissue samples obtained from the vastus lateralis after 60 min of exercise revealed that by 4 wk of training muscle lactate concentration, phosphocreatine hydrolysis, and glycogen depletion were depressed (all P < 0.05). Further training for 4 wk had no additional effect (P < 0.05). The ratio of fructose 6-phosphate to fructose 1,6-phosphate, an index of phosphofructokinase activity, was not altered with training. Muscle oxidative potential as estimated from the maximal activity of succinic dehydrogenase increased by 31% by 4 wk of training (P < 0.05) before plateauing during the final 4 wk of training. The increase in VO2max of 15.6% (P < 0.05) noted with training was also primarily expressed during the initial 4 wk. O2 uptake during submaximal exercise was unchanged. Because the metabolic response was similar in magnitude to that previously observed with short-term training, we conclude that, at least for the conditions of this study, the development of increased muscle aerobic potential is of minimal consequence on the magnitude of the energy metabolic adaptations examined.

Adaptation, Physiological↗
PubMed1995

Some operational aspects of school-milk fluoridation in St. Helens, Merseyside, UK.

St. Helens is a small industrial town situated about 20 km east of Liverpool. It lies in an area of social deprivation and, by UK standards, dental caries experience is high (e.g., dmft at 5 years = 2.8; DMFT at 12 years = 2.7). Water fluoridation is an important part of the government's strategy for improving oral health in such areas; however, in large parts of St. Helens, implementation of water fluoridation is complicated by reason of the multiple sources of water supply. The aims of the St. Helens study are therefore to examine the technical, organizational, and legal aspects of the fluoridation of school milk as an alternative public health approach. In the UK, children attending nursery units (kindergartens) from ages 2-4 years and infant schools from ages 4-7 years are eligible for 189 mL of milk to be consumed each day at school. These two schemes are funded or subsidized by the Departments of Health (UK) or the European Community, respectively. A preliminary review of the possibility of using school milk as a vehicle for fluoride has been published recently (Jones et al., 1992). The current paper will review progress over the past 12 months, including the response of schools, dairies, and other organizational considerations.

Animals↗
PubMed1995

Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.

PURPOSE: This prospective multicenter randomized trial was performed to compare the effectiveness and safety of intravenous (i.v.) vinorelbine tartrate (Navelbine [NVB]; Burroughs Wellcome Co, Research Triangle Park, NC) with i.v. melphalan (Alkeran [ALK]; Burroughs Wellcome Co) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer (ABC). Efficacy end points included time to disease progression (TDP), time to treatment failure (TTF), survival, tumor response rates, and quality of life (QL) and relief of cancer-related symptoms. PATIENTS AND METHODS: Between August 24, 1990, and December 1, 1992, 183 patients were randomized (2:1) to treatment with NVB (30 mg/m2 weekly) or ALK (25 mg/m2 every 4 weeks) i.v. Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center. RESULTS: Time to disease progression was significantly longer with NVB than with ALK, with a median 12 weeks versus 8 weeks, respectively (P < .001). NVB patients also had significantly longer time to treatment failure than ALK patients, with a median 12 weeks versus 8 weeks, respectively (P < .001). The effect of NVB on survival was also statistically significant (P = .034): 1-year survival rates were 35.7% with NVB and 21.7% with ALK and the median survival rate was 35 weeks and 31 weeks, respectively. In total, 46.5% of NVB patients and 28.2% of ALK patients achieved an objective response or stabilization of disease (P = .06). No intergroup differences were noted in patient-assessed QL and cancer-related symptoms. The most common toxicities were hematologic, including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK. Both drugs were generally well tolerated, and no septic deaths were reported. CONCLUSION: This randomized trial demonstrates a survival benefit in anthracycline-refractory ABC. NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC, without compromising QL. Based on activity of single-agent NVB in this difficult-to-treat patient population, investigations of NVB in combination with other anticancer drugs are warranted.

Adult↗
PubMed1995

Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

PURPOSE: We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS: A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS: The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION: Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

Adult↗
PubMed1995

Independent ventilation and ECMO for severe unilateral pulmonary edema after SLT for primary pulmonary hypertension.

Single lung transplantation (SLT) is now accepted therapy for selected cases of severe pulmonary hypertension. A recognized complication is the postoperative development of reperfusion edema in the graft, a potentially fatal cause of respiratory failure. Because reperfusion edema may be a reversible process, temporizing support measures can be life-saving. We report the case of a 48-year-old woman who developed severe reperfusion edema following right SLT for primary (unexplained) pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) was instituted. Independent lung ventilation was later begun and resulted in markedly improved oxygenation allowing withdrawal of ECMO. We conclude that reperfusion edema following SLT for pulmonary hypertension may be uniquely amenable to treatment with independent lung ventilation and ECMO if needed.

Extracorporeal Membrane Oxygenation↗
PubMed1995

Erythropoietic protoporphyria presenting in an adult.

Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra-violet light causing tissue damage by release of free oxygen radicals, which manifests as photosensitivity. The majority of cases of erythropoietic protoporphyria present in childhood although sometimes symptoms are delayed until the second decade. We report here a case presenting in adulthood and discuss the risk of liver disease in the condition.

Adult↗
PubMed1995

Staphylococcus aureus septic arthritis in patients on hemodialysis treatment.

We retrospectively reviewed hospital discharge diagnoses of septic arthritis over an 11-year period (1982 through 1992) at 3 medical centers; 11 episodes of septic arthritis were identified in patients on hemodialysis treatment. Of the 11 episodes, 9 were caused by Staphylococcus aureus; in 8 of 9, the blood cultures were positive for the organism and the infection was monoarticular. Concurrent infection of the dialysis access site occurred in 4 cases. Two patients died (22%). We postulate that repeated skin trauma and contact with health care personnel and facilities result in a high rate of nasal carriage of S aureus and, hence, an increased risk of bacteremia with its attendant complications such as septic arthritis. The use of mupirocin nasal ointment is reported to eradicate or suppress carriage in a high percentage of patients; some studies report that long-term suppressive therapy reduces the frequency of S aureus bacteremia.

Administration, Intranasal↗
PubMed1995

Influence in vitro of IL-3/Epo fusion proteins compared with the combination of IL-3 plus Epo in enhancing the proliferation of single isolated erythroid and multipotential progenitor cells from human umbilical cord blood and adult bone marrow.

Human interleukin-3/erythropoietin (IL-3/Epo) fusion protein have been constructed, expressed, and tested for biological activity. These fusion proteins were previously shown to be active on erythroid progenitors (BFU-E) from unseparated human bone marrow. We evaluated if these fusion proteins could stimulate erythroid and multipotential progenitor cells directly at the single-cell level. Two IL-3/Epo fusion proteins containing short (SL-3E, two amino acids) and long (LL-3E, 23 amino acids) linker sequences as well as a short linker Epo/IL-3 sequence (SL-E3, three amino acids) were tested. Highly enriched CD34 or BFU-E enriched CD34 CD33- cells from human umbilical cord blood or CD34 HLA-DR+CD33- cells from normal adult bone marrow were sorted as single cells into single wells. The combination of Epo plus IL-3 synergized to enhance the proliferation of BFU-E and multipotential progenitors (CFU-GEMM) in comparison to the individual effects of these cytokines. The three fusion proteins also enhanced proliferation of BFU-E and CFU-GEMM at the single-cell level and were at least as active as the combination of Epo and IL-3, demonstrating that IL-3/Epo fusion proteins directly stimulate proliferation of BFU-E and CFU-GEMM and that biological activity of IL-3 and Epo in vitro can be maintained when these proteins are fused. The activity of the combination of Epo and IL-3 or the fusion proteins was partially neutralized by preincubation with monoclonal antibodies to either Epo or IL-3 and was neutralized by greater than 90% by the combination of both antibodies, suggesting that the Epo and IL-3 components of the fusion proteins were both involved in the enhancing activity of these proteins. Additionally, use of monoclonal antibody to the human Epo receptor completely blocked the stimulating/enhancing activity of Epo alone, Epo plus IL-3, or the fusion proteins for stimulation of colony formation by BFU-E and CFU-GEMM but not for granulocyte-macrophage progenitors (CFU-GM), suggesting that the enhancing effects of the fusion proteins are most likely mediated, at least in part, by the Epo receptor.

Bone Marrow Cells↗