Search PubMed⌕ Search

Biomedical subjects

J Barnes

Publications and source records attributed to J Barnes.

At least 19 recordsLinked to original sources
PubMed1992

Impaired bone activity in aged rats: alterations at the cellular and molecular levels.

We have used a model of rapid bone induction and resorption in rats initiated by the removal of bone marrow to define age-associated deficits. Here we report the sequential expression of various genes implicated in the formation and removal of bone following marrow ablation. Significant increases in alkaline phosphatase and procollagen alpha 1(I) mRNA were observed by day 5, and of osteocalcin and osteopontin by day 6. At their peak, these mRNA levels were elevated three- to eight-fold and correlated with histological evidence of bone formation. No change in collagen II mRNA was observed, indicating that there was no cartilage phase. Collagenase activity increased 10-fold at day 9 and coincided with the beginning of bone resorption. Actin mRNA, a reference gene marker, remained at constant levels. Comparison of the response between adult (6 mo.) and old (24 mo.) rats showed the same temporal pattern, but a lower expression of bone-related genes in older rats. Histological examination also showed that the bone volume and osteoblast number at day 6 were significantly lower in old rats. Furthermore, the percentage of mineralized bone was greatly reduced in the aged rat. This model system is currently being used to evaluate the effectiveness of interventions to up-regulate the bone activity in senescent rats.

Aging↗
PubMed1992

Measurement of capillary cholesterol as an aid to the management of hypertensive patients with hyperlipidaemia--an assessment of the Reflotron.

The Reflotron dry chemistry method of capillary cholesterol measurement has been widely adopted as a rapid means of population screening. We attempted to use it to monitor changes in cholesterol in a trial of intensive dietary intervention in hyperlipidaemic hypertensives. Four hundred and eighty-nine capillary cholesterol levels measured by the Reflotron were compared with levels for venous samples obtained simultaneously and assayed by the Biochemistry Department using conventional laboratory methods. The mean difference between them was 0.3 mmol/l +/- 0.8 (SD). Approximately one-third of the variability in the difference between the two methods was explained by the variables, Reflotron machine used and time (R2 = 54%, adjusted R2 = 34%). We conclude that the Reflotron is not suitable for accurate assessment of the modest changes in cholesterol which occur in individual patients during dietary intervention.

Blood Chemical Analysis↗
PubMed1991

Effect of tachykinins in small human airways.

We have compared the contractile responses of substance P (SP) and neurokinin A (NKA) to that of the non degradable muscarinic agonist, carbachol, in small and large human airways in vitro. We have also investigated the effects of the neutral endopeptidase (NEP) inhibitor, thiorphan (100 microM) on these responses. NKA contracted large and small airways to a different extent (56% vs 92% of carbachol maximal contraction, respectively). NKA was significantly less potent in large vs small bronchi (EC50 = 150 +/- 15 vs 12 +/- 5 nM respectively, p less than 0.05). SP had a lower contractile effect in large (26% carbachol maximum) and small airways (59%) with EC50 values higher than 0.5 microM. The enkephalinase inhibitor thiorphan shifted the concentration-response curve to NKA to the left in large (EC50 = 35.2 +/- 8.2 nM) and small bronchi (EC50 = 2.8 +/- 1.3 nM, p less than 0.02). This shift was associated with an increase in the maximal contraction to NKA (75% in large vs 123% in small bronchi). The amplitude of contraction to SP was also potentiated in large (45%) and in smaller bronchi (101%). In conclusion, we have demonstrated that NKA has a significantly greater constrictor effect than a cholinergic agent in more peripheral human airways in vitro. This suggests that non cholinergic constrictor pathways are more likely to be important in more peripheral airways.

Bronchi↗
PubMed1991

Alterations of duodenal vitamin D-dependent calcium-binding protein content and calcium uptake in brush border membrane vesicles in aged Wistar rats: role of 1,25-dihydroxyvitamin D3.

Previously we reported that uptake of Ca2+ in cells isolated from rat duodenum declined in senescence. In this paper we examined the possible mechanisms for this age-related defect. Duodenal vitamin D-dependent calcium-binding protein decreased steadily from 3-12 months (mo), followed by a minimal decline at 24 mo. On the contrary, Ca2+ uptake was not different in 3-, 6-, and 12-mo-old rats. A significant decline of Ca2+ uptake was observed at 24 mo. ATP contents in duodenal cells from 6- and 24-mo-old rats were not different. This suggests that the metabolic status of the duodenal cells was not the cause of the change in Ca2+ uptake. Ca2+ uptake activity was significantly lower in brush border membrane vesicles isolated from 24-mo-old rats than in those from 6-mo-old rats. The decrease in Ca2+ uptake activity in old rats was not due to a change in the Ca2(+)-binding capacity of the membranes. Kinetic analysis shows that the Vmax, the apparent maximum uptake capacity of membrane vesicles, decreased in senescent rats, whereas the Km, the apparent affinity to Ca2+, was unchanged. Since duodenal Ca2+ influx at the brush border was regulated by 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3], we tested the effect of 1,25-(OH)2D3 administration on the uptake activity in isolated membrane vesicles. After 1,25-(OH)2D3 treatment, Ca2+ uptake activity in brush border membranes prepared from senescent rats was only slightly lower than that in membranes from adult rats. We conclude that the decline in the influx of Ca2+ at the brush border membrane was the main cause of the decrease in duodenal Ca2+ uptake activity in aging. This defect was probably due to the low serum 1,25-(OH)2D3 concentration and not the result of impaired response to 1,25-(OH)2D3.

Adenosine Triphosphate↗
PubMed1991

Distribution of electron trapping in DNA: protonation of one-electron reduced cytosine.

Electron spin resonance was employed to study one-electron reduced cytosine stabilized in glasses at low temperatures. In a LiCl/H2O glass, deoxycytidine gives an extra approximately 1 mT splitting that is not observed in oligomers. To better understand the source of the extra splitting, 1-methylcytosine (1mC) and N,N-dimethyldeoxycytidine (dmC) were examined in an HCl/H2O glass. The spectrum of 1mC is a quartet and the spectrum of dmC is a triplet. A probable explanation for this is that in both cases N4 is fully protonated prior to electron addition. In the LiCl/H2O glass, monomeric cytosine, after one-electron reduction, appears to protonate at N4. However, oligomeric cytosine, after one-electron reduction, does not protonate at N4 and therefore must protonate at N3. This could be due to the exclusion of Li+ coordination at N3 and/or the constraining of N4 to a planar configuration via stacking interactions. These findings provide additional insight into why cytosine is the major site of electron capture in DNA. Proton transfer across the N1-H...N3 hydrogen bond is expected to stabilize electron addition to cytosine preferentially.

Cytosine↗
PubMed1991

Pharmacoepidemiology of ciprofloxacin: analysis of use patterns and cost impact.

The pharmacoepidemiology and cost impact of ciprofloxacin use were evaluated after unrestricted availability in a 238-bed community teaching hospital. The medical records on all patients treated with oral ciprofloxacin over 6 months were reviewed. To determine if the availability of ciprofloxacin altered antibiotic usage patterns and outcome variables, a group of control patients from a period prior to ciprofloxacin availability were matched and compared to patients who had received the drug. Ciprofloxacin was used as both initial and replacement for parenteral therapy in a variety of infections. A successful clinical outcome was achieved in approximately 90% of patients treated with ciprofloxacin and resulted in an estimated cost avoidance of approximately $165/course. However, comparisons with the matched-control group revealed no differences in overall antibiotic costs or length of hospital stay. These results suggest that unrestricted availability of oral ciprofloxacin does not ensure changes in outcome variables related to cost. Educational and patient targeting programs may be necessary to promote earlier conversion of appropriate patients to newer oral therapies.

Administration, Oral↗
PubMed1990

Treatment of clinical stage I Hodgkin's disease by local radiation therapy alone. A United Kingdom Childrens Cancer Study Group study.

The UKCCSG study of the treatment of Hodgkin's disease between January 1982 and January 1988 accrued 209 patients. Of these, 59 had clinical Stage I disease. These 59 patients were treated with radiation therapy alone to sites of initial involvement. In case of relapse, combination chemotherapy was used. With a median follow-up of 3 years, 50 patients are alive with no evidence of disease after radiation therapy alone. Nine patients have relapsed between 5 and 55 months (median time to relapse, 18 months). Eight patients have been successfully treated with combination chemotherapy and are alive with no evidence of disease (one of these patients having had two relapses). One patient has died after widespread relapse. Of the 59 Stage I disease patients, 85% are relapse free after single-modality treatment. Overall survival is 98%. Long-term complications are minimal at this stage but long-term follow-up is essential.

Adolescent↗
PubMed1990

'MACHO' chemotherapy for stage IV B cell lymphoma and B cell acute lymphoblastic leukaemia of childhood. United Kingdom Children's Cancer Study Group (UKCCSG).

An intensive 6-month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym 'MACHO', to treat 24 newly and consecutively diagnosed children, 13 with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) and 11 with B-cell acute lymphoblastic leukaemia (B-ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS+) received planned additional megatherapy/bone marrow transplants. Event-free survival (EFS) at 1 year for the 11 cases of B-ALL is 64% (95% confidence intervals [CI] 31-89%) and of 13 stage IV B-NHL cases is 50% (95% CI 19-75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13-68%) compared with 76% (CI 39-94%) for those without bulky abdominal disease. Overall EFS for eight CNS+ patients is 73% at 1 year (95% CI 34-97%) compared with 48% (95% 24-74%) for those without CNS disease (CNS-). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P less than 0.5). A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or 1 fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49-95%] versus 24% [6-65%], P less than 0.04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B-ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy.

Adolescent↗
PubMed1989

Effect of age on calcium uptake in isolated duodenum cells: role of 1,25-dihydroxyvitamin D3.

Uptake of Ca2+ in cells isolated from rat duodenum declined in the senescent rats. This age-related change was not due to an alteration in the rate of Ca2+ efflux or in the size of the cell. The decrease appeared specific, as alpha-methyl glucoside uptake was not altered. Cell population, as monitored by sucrase activity for villus cells, was not different between duodenal cells isolated from 6- and 24-month-old rats. Kinetic analysis shows the Vmax, the apparent maximum uptake capacity, decreased in the cells from senescent rats whereas the Km, the apparent affinity to Ca2+, was unchanged. Serum levels of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were determined as a function of age; the levels of 25OHD were not significantly different in 3-, 6-, 12-, and 24-month-old rats. On the other hand, serum 1,25-(OH)2D decreased throughout the age range studied. Since duodenal Ca2+ uptake is closely regulated by 1,25-(OH)2D3, we tested the hypothesis that low serum 1,25-(OH)2D in the senescent rats may have contributed to the decline in duodenal Ca2+ uptake. In vivo administration of 1,25-(OH)2D3 to senescent rats significantly enhanced Ca2+ uptake activity in the isolated duodenal cells. After 1,25-(OH)2D3 treatment, Ca2+ uptake activity in cells isolated from senescent rats was only slightly less than that in cells from adult rats. We conclude that duodenal Ca2+ uptake declined in the senescent rats, and this age-related change was most likely due to the low serum level of 1,25-(OH)2D and not the result of a decrease in any duodenal response to 1,25-(OH)2D3.

Aging↗
PubMed1989

Hypothermia protects brain function in acute carbon monoxide poisoning.

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.

Animals↗
PubMed1989

N-cadherin of the human lens.

N-cadherin was identified in the human lens by its immunological specificity, and concanavalin-A (Con-A) binding. The 135 kd glycoprotein was partially purified from human lens plasma membranes by Con-A affinity column chromatography. In the newborn lens, N-cadherin is distributed equally in amount between cortical and nuclear membranes. It is markedly decreased in the nuclear membranes of the 2 year-old lens and was no longer detectable in the nucleus of 15 yr-old and older lenses (15 yrs - 86 yrs). Such nuclear loss of N-cadherin is consistent with similar findings in the chicken and bovine lens. At all ages, N-cadherin was readily detected in cortical fiber-cells. When expressed as a ratio to MP26 content, the amount of N-cadherin of the total fiber mass declines at least 4-fold from newborn to 15 years of age, and remains stable thereafter. Homogenization of bovine lenses in the presence of Ca++ resulted in a marked loss of the protein, suggestive of degradation by a calcium-activated protease. The loss of N-cadherin with aging in fiber cells suggests either an alteration in the mode of membrane adhesion of these cells, or a decline in adhesiveness of nuclear as compared to cortical fiber-cells.

Adolescent↗