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Biomedical subjects

J Barnes

Publications and source records attributed to J Barnes.

At least 109 records · Page 6Linked to original sources

Adenocarcinoma of the colon presenting with a Sister Mary Joseph's nodule and Trousseau's syndrome.

We describe an unusual case of colon cancer presenting with two dermatologic manifestations of internal malignancies: Trousseau's syndrome and Sister Mary Joseph's nodule. Trousseau's syndrome is associated with 1 to 11 percent of internal malignancies, while 5 percent of colorectal carcinomas present with cutaneous metastases. Our case highlights the clinical significance of dermatologic signs of occult gastrointestinal malignancies.

Abdominal Neoplasms↗

Combination is the dominant free radical process initiated in DNA by ionizing radiation: an overview based on solid-state EPR studies.

An overview of the early processes initiated in DNA by ionizing radiation is given from the perspective of studies done by solid-state EPR with the focus on radical combination. Comparisons with free radical formation and trapping in crystalline pyrimidines (1-methylcytosine, thymine, 1-methylthymine, 1-methyluracil, and cytosine monohydrate) provide insight into the processes occurring in DNA. Between 25 and 50% of low LET ionizations in fully hydrated DNA at 4 K lead to trapped free radicals, the remaining unobserved radicals are assumed to have combined. The majority of the radicals trapped in DNA at 4 K (G approximately 0.3 mumol/J) are believed to be in clusters. Based on the value of G, it is argued that the range of holes and bound electrons in DNA at 4 K are, in the main, limited to within the cluster diameter, approximately 4 nm. Proton transfer across hydrogen bonds promotes radical trapping and inhibits combination but is thermally reversible. Warming to room temperature mobilizes the reversibly trapped radicals and gives additional combination (50-80% of those trapped at 4 K). The yield of free radicals, after anneal, is sufficient to account for the yield of single-strand breaks produced by direct effects.

DNA↗

The influence of packing on free radical yields in crystalline nucleic acids: the pyrimidine bases.

The total free radical yield has been measured for crystals of five pyrimidine derivatives: thymine (T), 1-methylthymine (1MeT), 1-methyluracil (1MeU), 1-methylcytosine (1MeC) and cytosine monohydrate (C:HOH). Q-band EPR measurements were made on samples X-irradiated between 4 and 12 K. The G values in units of 10(-7) mol/J are 1MeC < 0.01, T < 0.04, 1MeU = 0.15, 1MeT = 0.25, and C:HOH = 0.8. The types of free radicals formed in these crystals are known through previous EPR investigations. A model is presented that attempts to identify the salient variables behind the large range in G values and, simultaneously, explain the variation in radical types. It is concluded that packing is a critical variable. Hydrogen-bonding networks promote the trapping of radicals through reversible proton transfer. In the absence of such a network less probable radical types are observed, such as radicals formed by irreversible protonation/deprotonation, higher-order reactions and homolytic bond cleavage. Crystals with low G values trap radicals formed predominantly by irreversible protonation/deprotonation at carbon positions and by excitation-spawned homolytic bond cleavage. In contrast, crystals with high G values trap radicals formed predominantly by reversible protonation/deprotonation at heteroatom positions. This model is extended to polynucleotides irradiated at low temperatures, where G values are typically 2-6. The high trapping efficiency seen in polynucleotides reflects highly efficient proton transfer. Consistent with this is the predominance of radicals formed by reversible protonation/deprotonation compared to those formed by irreversible protonation/deprotonation.

Crystallization↗

Characterization of dietary phosphorus-dependent duodenal calcium uptake in vitamin D-deficient chicks.

The effect of dietary phosphorus on intestinal calcium uptake was examined in duodenal cells isolated from vitamin D-deficient chicks. Cells from chicks on a high phosphorus diet accumulated calcium at a rate 38% higher than cells from animals on a normal phosphorus diet. Diet high in calcium did not affect calcium absorption in duodenal cells. The dietary phosphorus effect on calcium absorption was specific. Uptake of alpha-methyl glucose was not altered. Increase in calcium absorption by a high phosphorus diet was not due to a change in cellular energy metabolism nor to the content of phosphorus in cells. Kinetically, a high phosphorus diet increased the Vmax of calcium uptake; the affinity for calcium was unaffected. The effectiveness of dietary phosphorus to enhance the intestinal calcium uptake could also be demonstrated in brush border membrane vesicles. The increase in calcium uptake was not due to an alteration in membrane binding capacity nor to calcium efflux from vesicles. To test the hypothesis that a high phosphorus diet may affect membrane transport by altering phospholipid metabolism in duodenal cells, we examined the phospholipid content in isolated brush border membranes. The content of phosphatidylcholine, phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine was not altered by the high phosphorus diet. These findings suggest that the vitamin D-independent and dietary phosphorus-dependent effect on intestinal calcium absorption was primarily due to a change in the calcium flux at the luminal side of the cells. However, the precise mechanism is still not clear.

Administration, Oral↗

Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause.

OBJECTIVE: Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women. DESIGN: In a placebo controlled, double-blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period of 16 weeks. PATIENTS: Seventeen women aged 28-51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n = 12) or placebo (n = 5) group. MEASUREMENTS: Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non-parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs. RESULTS: After 16 weeks of treatment, HDL cholesterol, apo A-I and HDL-2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A-I +14%, P < 0.01; HDL-2 +24% P < 0.01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion and concentration of the least dense LDL-I subfraction was decreased significantly (-27%, P < 0.05). The LDL subfraction of intermediate density (LDL-II) was decreased in eight subjects, while small, dense LDL-III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL-III, although there was no net increase in the latter. CONCLUSION: In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL-I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.

Adult↗

Decrease in Gs protein expression may impair adenylate cyclase activation in old kidneys.

The possibility that alteration in stimulatory guanine nucleotide-binding protein (Gs) expression may contribute to the blunting of renal parathyroid hormone (PTH)-stimulated adenylate cyclase in aged rats was examined. Using rat cDNA probe, we identified a Gs alpha-subunit (Gs alpha) of 1.9 kb. Age did not alter the size of Gs alpha mRNA. The level of Gs alpha mRNA [normalized to poly(A)+ RNA] was decreased 23%, which was consistent with our previous report that Gs alpha protein decreased in senescence. In contrast, mRNA level of Gi alpha 2 increased with age. Level of beta-actin mRNA did not change with age. Nuclear runoff assay was performed to determine the transcription rate of Gs mRNA. Synthesis of poly(A)+ RNA and total RNA was reduced 39% and 37%, respectively, in nuclei prepared from old kidney, which suggested a general decline in RNA synthesis capacity in old rats. Our results also showed the transcription rate of Gs alpha mRNA in aged rats was reduced 89%, a decrease far exceeding that observed for total RNA or poly(A)+ RNA. We concluded that the decrease in steady-state level of Gs alpha mRNA was specific and probably was due to a reduction in the transcription activity. Thus alteration in Gs transcription may contribute, at least in part, to the impaired renal adenylate cyclase activation in aged rats.

Adenylyl Cyclases↗

The last resort? Bed and breakfast accommodation for mentally ill people in a seaside town.

There have been few studies about the seaside hotel accommodation provided for mentally ill people in the United Kingdom, despite its extensive use. This paper reports the findings of a survey in Southend, which compared living conditions and residents in bed and breakfast accommodation with those in sheltered accommodation for mentally ill adults. The results show that the mentally ill residents of bed and breakfast accommodation were living in less attractive and less well maintained surroundings. They were not only more likely to have been recently discharged from a psychiatric unit, but also had less contact with the range of community mental health services. Residents in bed and breakfast accommodation were, however, closer to local amenities, such as day centres and parks, than the control group. Staff practices were less restrictive in bed and breakfast accommodation than in the majority of sheltered homes; homes employing psychiatric nurses allowed residents the most freedom. These findings support the need for more accommodation of an acceptable standard for those people discharged from psychiatric units. Local liaison schemes between health workers responsible for the continuing care of mentally ill people and the landlords of bed and breakfast accommodation could improve the quality of life for these residents.

England↗

[Manner of birth and otitis media].

BACKGROUND: There are many risk factors associated with the occurrence of otitis media; cesarean section could be one of them. REPORT: Two hundred and eighty four children were treated during the first three years of life by the same pediatric service. 47% of these children were treated for otitis media and 53% were not. 41% were delivered by cesarean section, and 59% were vaginal births. The incidence of otitis media in the cesarean section group was 0.504, versus 0.449 in the vaginal birth group. RESULTS: These data indicate that the fraction of risk of having otitis media that is attributable to cesarean section is 11%; the relative risk is 1.12. CONCLUSION: The observed effect is not large enough to confirm that cesarean section is a risk factor, but suggests that a carefully controlled prospective study should be conducted.

Cesarean Section↗

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↗

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↗

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↗