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Biomedical subjects

S Ball

Publications and source records attributed to S Ball.

At least 109 records · Page 6Linked to original sources

Excitotoxin induction of ornithine decarboxylase in cerebral cortex is reduced by phospholipase A2 inhibition.

The enzyme ornithine decarboxylase (ODC) has been shown to be induced by a number of conditions such as cold-injury, kindling, ischaemia and excitotoxin injection. In previous studies we have characterised the cortical response to kainate injection into the nucleus basalis and shown a substantial increase in both ODC mRNA and enzyme activity which reaches a maximum at 8h. This response is completely prevented by treatment with MK-801, indicating the involvement of NMDA receptors in mediating this response. Whilst NMDA receptors are known to gate a cation channel leading to increased calcium entry, an additional effect on the release of arachidonic acid has been reported. The possibility that NMDA receptor mediated activation of phospholipase A2 and release of arachidonic acid might mediate this ODC response was investigated in this study by treatment with the phospholipase inhibitors quinacrine and dexamethasone. Treatment of animals with quinacrine (100 mg/kg) at the time of injection of kainate into the nucleus basalis caused a significant attenuation of the induction of ODC in cerebral cortex of 43%. No further attenuation was seen at higher doses. A similar reduction in ODC induction was seen after treatment with dexamethasone (1 mg/kg) but a greater effect could be obtained (65% attenuation) at higher doses. The possible involvement of arachidonic acid derivatives in mediating ODC induction was further investigated by treatment with the cyclo-oxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Indomethacin was able to significantly attenuate the induction of ODC (greater than 60%) whilst NDGA (30 mg/kg) was ineffective. These results indicate the possible role of arachidonic acid derivatives in the regulation of the expression of ODC in cerebral cortex after excitotoxin injection.

Animals↗

Waxy Chlamydomonas reinhardtii: monocellular algal mutants defective in amylose biosynthesis and granule-bound starch synthase activity accumulate a structurally modified amylopectin.

Amylose-defective mutants were selected after UV mutagenesis of Chlamydomonas reinhardtii cells. Two recessive nuclear alleles of the ST-2 gene led to the disappearance not only of amylose but also of a fraction of the amylopectin. Granule-bound starch synthase activities were markedly reduced in strains carrying either st-2-1 or st-2-2, as is the case for amylose-deficient (waxy) endosperm mutants of higher plants. The main 76-kDa protein associated with the starch granule was either missing or greatly diminished in both mutants, while st-2-1-carrying strains displayed a novel 56-kDa major protein. Methylation and nuclear magnetic resonance analysis of wild-type algal storage polysaccharide revealed a structure identical to that of higher-plant starch, while amylose-defective mutants retained a modified amylopectin fraction. We thus propose that the waxy gene product conditions not only the synthesis of amylose from endosperm storage tissue in higher-plant amyloplasts but also that of amylose and a fraction of amylopectin in all starch-accumulating plastids. The nature of the ST-2 (waxy) gene product with respect to the granule-bound starch synthase activities is discussed.

Alleles↗

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.

Blood Loss, Surgical↗

An experimental investigation of thought suppression.

An experiment investigating the hypothesis that trying to suppress a thought will lead to an immediate and/or delayed increase in its occurrence is reported. Normal subjects listened to a taped story and then verbalized their stream of consciousness during two consecutive time periods. During the first period, one group (suppression) were asked not to think about the tape while two other groups (controls) were asked to think about anything or think about anything including the tape. During the second period, all three groups were instructed to think about anything. Results from the first period failed to support the immediate enhancement hypothesis as the suppression group reported less thoughts about the tape than the controls. However, results from the second period supported the delayed (rebound) hypothesis as subjects who had previously suppressed reported more thoughts about the tape than subjects who had not. The theoretical, methodological, and clinical implications of these results are discussed.

Adult↗

Hypoglycaemia associated with anorexia nervosa.

A 41 year old woman with severe emaciation due to longstanding anorexia nervosa presented with recurrent hypoglycaemia. During an episode of hypoglycaemia, serum insulin and C peptide were undetectable and plasma beta hydroxybutyrate, free fatty acids and lactate were inappropriately low. Response to intravenous glucagon was poor. Muscle enzymes were grossly elevated until she gained weight. Hypoglycaemia was abolished by weight gain.

Adult↗

Influences of sensation seeking, gender, risk appraisal, and situational motivation on smoking.

The study evaluated the current relationship between the trait of sensation seeking and smoking as possibly mediated by gender, cognitive risk appraisal and situational-relevant motivation. Subject were 1071 male and female undergraduates of whom 279 indicated they were past or current smokers and completed a Smoking Questionnaire (SQ). All subjects took the Sensation Seeking Scale. Sensation seeking is significantly (p less than .001) related to the proportion smoking in both men and women, although more women at the university are now smoking. Sensation seekers inhaled more of the smoke than lows, perhaps an indication of stronger nicotine need. Smoking was seen as highly risky, but the degree of estimated risk was not related to sensation seeking. Women reported smoking more in emotional and social situations; men reported smoking more in situations requiring close attention to a task. Sensation seekers reported smoking more than lows in social situations. Research is needed on specific cognitive factors mediating smoking and how they are related to personality and gender.

Adult↗

Mapping of mouse carbonic anhydrase-3, Car-3: another locus in the homologous region of mouse chromosome 3 and human chromosome 8.

At least six separate genes determining tissue- and organelle-specific isoforms of carbonic anhydrase are known. We have determined the chromosome location of one of these genes, carbonic anhydrase-3 (Car-3), in the mouse and carried out a linkage analysis of Car-1, Car-2, and Car-3. Car-3 has been assigned to band 3A2 by in situ hybridization. We identified a PstI restriction fragment length polymorphism between Mus spretus and Mus mus domesticus and, by using an interspecific backcross, showed that Car-3 is 2.4 +/- 1.7% SE from both Car-1 and Car-2, calculating genetic distance as percentage recombination. No recombinants were found between Car-1 and Car-2 in 100 backcross offspring, and when these data are combined with earlier results, these two loci are estimated to be 1.2 cM from each other at the 95% confidence interval. The three homologous carbonic anhydrase loci in man had earlier been assigned to 8q22, and the finding of linkage of Car-3 to Car-1 and Car-2 in the mouse adds another locus to the conserved segments on mouse chromosome 3 and human chromosome 8.

Animals↗

The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.

The X chromosome-linked scurfy (sf) mutant of the mouse is recognized by the scaliness of the skin from which the name is derived and results in death of affected males at about 3-4 weeks of age. Consideration of known man-mouse homologies of the X chromosome prompted hematological studies, which have shown that the blood is highly abnormal. The platelet and erythrocyte counts are both reduced and become progressively lower relative to normal as the disease progresses. There is gastrointestinal bleeding, and most animals appear to die of severe anemia. By contrast, the leukocyte count is consistently raised. Some animals showed signs of infection but it is not yet clear whether there is immunodeficiency. Other features include the scaly skin and apparently reduced lateral growth of the skin, conjunctivitis, and diarrhea in some animals. The mutant resembles Wiskott-Aldrich syndrome in man, which is characterized by thrombocytopenia, eczema, diarrhea, and immunodeficiency. The loci of the human and mouse genes lie in homologous segments of the X chromosome, although apparently in somewhat different positions relative to other gene loci. Scurfy differs from Wiskott-Aldrich syndrome in that scurfy males are consistently hypogonadal.

Aging↗

Use of Nd-Yag laser ablation in colorectal obstruction and palliation in high-risk patients.

Conventional treatment for colonic obstruction due to cancer or benign anastomotic strictures in high-risk patients or unresectable cases in some form of colostomy. This procedure has the negative aspects of requiring a general anesthetic and leaves the infirm patient with a stoma that they cannot easily attend to. Ablation of tumor by Nd-Yag laser has been available for several years, with passage of the laser fiber through a colonoscope. To evaluate the role of laser photocoagulation in the palliation of colorectal tumors or benign strictures, the authors summarized their initial experience, trying to define the indications, various methods of treatment, and complication rate in these patients. This technique is difficult to perform and has the added risk of intestinal perforation but does obviate anesthetic and surgical risks. Seven patients with recurrent metastatic colorectal obstruction, three patients with benign colonic strictures, and two patients with large villous tumors were treated with Nd-Yag laser passed via the colonoscope. The mean age was 71 years (range, 52 to 86 years). Five patients received sedatives only, six patients received epidural anesthetic, and one had a general anesthetic. The average total energy used was 3702 joules on noncontact fibers, and the average number of pulses was 126. Distance of the lesion from the anal margin ranged from 0.5 to 30 cm. Ten of twelve tumors were within 15 cm of the dentate line. In the most distal lesions, manual debulking with biopsy forceps facilitated the laser treatment. Symptomatic relief was achieved in all patients. One patient required a colostomy one month after treatment because of incontinence. Another patient needed a resection of a benign stricture after three laser treatments. Other than one case of microperforation, treated conservatively with antibiotics, no other complications occurred and there was no mortality. The authors believed that the Nd-Yag laser plays a specific role in the treatment of high-risk patients.

Aged↗

Enprostil inhibits post-prandial gastrin release: a dose-response study.

In a double-blind placebo-controlled study in nine healthy volunteers, the effects of single doses of oral enprostil (8.75, 17.5, 35 and 70 micrograms), taken before a standard breakfast, were assessed on the post-prandial release of gastrin into the plasma. All doses of enprostil caused a significant dose-related decrease in median post-prandial plasma gastrin concentration (range from -29 to -44%). In the same subjects, two doses of 25 mg indomethacin caused a significant (38%) increase in median post-prandial plasma gastrin concentration.

Adult↗

Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia.

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.

Adult↗

Twenty-four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole.

Simultaneous 24-hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty-eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24-hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol.hour litre-1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24-hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol.hour litre-1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24-hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious-anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin-like cell proliferation in duodenal ulcer patients.

Adult↗

Localization of the gene for X-linked spinal muscular atrophy.

We used probes for DNA polymorphisms on the X chromosome to study genetic linkage in seven families with X-linked adult-onset spinal muscular atrophy. We found significant linkage to the marker DXYS1 on the proximal X chromosome long arm and loose linkage or nonlinkage to markers elsewhere. Our analysis localizes the gene defect for this form of anterior horn cell disease.

Adult↗