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Biomedical subjects

J Gale

Publications and source records attributed to J Gale.

At least 19 recordsLinked to original sources

The high oxygen atmosphere toward the end-Cretaceous; a possible contributing factor to the K/T boundary extinctions and to the emergence of C(4) species.

Angiosperm plants were grown under either the present day 21 kPa O(2) atmosphere or 28 kPa, as estimated for the end-Cretaceous (100-65 MyBP). CO(2) was held at different levels, within the 24-60 Pa range, as also estimated for the same period. In C(3) Xanthium strumarium and Atriplex prostrata, leaf area and net photosynthesis per unit leaf area, were reduced by the high O(2), while the whole-plant respiration/photosynthesis ratio increased. The high O(2) effects were strongest under 24 Pa, but still significant under 60 Pa CO(2). Growth was reduced by high O(2) in these C(3) species, but not in Flaveria sp., whether C(3), C(4), or intermediary grown under light intensities <350 micromol m(-2) s(-1) PPF. Photosynthesis of C(3) Flaveria sp. was reduced by high O(2), but only at light intensities >350 micromol m(-2) s(-1) PPF. It is concluded that the high O(2) atmosphere at the end-Cretaceous would have reduced growth of at least some of the vegetation, thus adversely affecting dependent fauna. The weakened biota would have been predisposed to the consequences of volcanism and the K/T boundary bolide impact. Conversely, photosynthesis and growth of C(4) Zea mays and Atriplex halimus were little affected by high, 28 kPa, O(2). This suggests an environmental driver for the evolution of C(4) physiology.

Atmosphere↗

The cochlea.

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Adaptation, Physiological↗

Cognitive behaviour therapy: teaching a client the ABC model--the first step towards the process of change.

Research suggests that clients need to be made aware of the relationship between thinking and emotional and behavioural reactions at the start of the therapeutic work. This paper looks at the clinical processes of educating the client about this relationship in a seven-step ABC model. Rationales for each of the seven steps are given. The model illustrates the process of generating alternative beliefs in relation to a negative event and shows consequences of holding helpful and unhelpful beliefs.

Affective Symptoms↗

Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center.

PURPOSE: We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women). PATIENTS AND METHODS: Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records. RESULTS: Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively. CONCLUSION: The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.

Actuarial Analysis↗

The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat.

The purpose of this study was to investigate the pharmacological properties of the novel, selective 5-HT3 receptor antagonist, alosetron, and its effects on transit time in both the normal and perturbed small intestine of the rat. Alosetron concentration-dependently inhibited radioligand binding in membranes containing rat and human 5-HT3 receptors with estimated pKi values of 9.8 (n = 3) and 9.4 (n = 6), respectively. In selectivity studies alosetron had little or no significant affinity for any of the many other receptors and ion channels studied. Alosetron potently antagonized the depolarization produced by 5-HT in the rat vagus nerve (estimated pKB value of 9.8, n = 25). In anaesthetized rats, i. v. administration of alosetron inhibited 2-methyl-5-HT induced bradycardia (Bezold Jarisch index) at 1 and 3 microg kg-1, with an agonist dose ratio of approximately 3.0 at 1.0 microg kg-1, = 3-5). Alosetron administered via the duodenum also inhibited this reflex, with duration of action that was significantly longer than that seen with ondansetron (120-60 min, respectively, n = 6). Alosetron had no significant effect on normal small intestinal propulsion in the rat, but fully reversed the increase in intestinal propulsion (96%, n = 3) produced by egg albumin challenge. Alosetron is a highly selective 5-HT3 antagonist which normalizes perturbed small intestinal propulsion. Previous clinical data in IBS patients together with the transit data provide a good rationale for further studies with alosetron in IBS patients.

Adrenergic alpha-Agonists↗

An evaluation of vital registers as sources of data for infant mortality rates in Cameroon.

BACKGROUND: Infant mortality rates have been widely used as indicators of health status and the availability, utilization and effectiveness of health services. Two principal sources of data for infant mortality rates are vital registers and censuses. This study was designed to evaluate the accuracy of vital registers as sources of data for infant mortality rates in Cameroon. METHODS: A household census of births and infant deaths that occurred in Buea Subdivision between 1 November 1991 and 31 October 1992 was conducted to determine the proportion that were registered and the reasons why the remainder were not registered. RESULTS: The registration coverage was found to be 62% for births and 4% for infant deaths. The most frequently reported reasons for not registering births were lack of money, lack of time and a complicated registration procedure. For infant deaths the reasons were lack of knowledge and no perceived benefits. CONCLUSIONS: Vital registers of birth and death are not an accurate source of data for infant mortality rates in Cameroon. Motivation for birth and death registration appear to be dependent on the perceived benefits. A mechanism of registration that uses medical institutions may substantially increase registration coverage for births and infant deaths.

Birth Certificates↗

Intestinal metaplasia in stilboestrol-induced vaginal adenosis.

We present an unusual case of vaginal adenosis with progressive intestinal metaplasia, previously undescribed, in a female patient exposed to stilboestrol in utero. Argentaffin cells were present within these areas, a feature not previously reported in benign vaginal adenosis. The development of the intestinal metaplasia coincided with the onset of a vaginal discharge so severe that, after 7 years, a vaginal resection was performed. Intestinal-type glands have been described in the cervix and ovary, almost invariably associated with malignancy. The possible role of intestinal metaplasia in the development of enteric-type neoplasms of the vagina is discussed.

Adult↗

The use of maleimidocaproyloxysuccinimide to prepare malarial peptide carrier immunogens. Immunogenicity of the linking region.

Malarial peptides synthesized with an added N terminal cysteine were conjugated to purified diphtheria toxoid (DT) protein using the bifunctional reagent maleimidocaproyloxysuccinimide (MCS). The molar ratio of peptide to carrier was determined by subtractive sulphydryl titration and confirmed by sodium dodecyl sulphate (SDS) electrophoresis. For enzyme-linked immunoabsorbent (ELISA) analysis of sera from animals immunized with the DT conjugates, peptides were conjugated to bovine serum albumin (BSA) using MCS as well as a glutaraldehyde based coupling procedure. Western blotting analysis shows that both DT and BSA adducts were recognized by monoclonal antibodies (Mabs) directed against the peptide epitopes in the native sequences. Animals immunized with the DT-peptide conjugates produced antibodies to the coupling reagent (MCS) as well as diphtheria toxoid and peptide specific antibodies. This MCS specificity could be largely abolished by pre-incubation of sera with a soluble MCS homologue, a thiosuccinimidocaproylamide (TSC).

Amino Acid Sequence↗

Carbon balance and productivity of Lemna gibba, a candidate plant for CELSS.

The photosynthesis and productivity of Lemna gibba were studied with a view to its use in Controlled Ecological Life Support Systems (CELSS). Photosynthesis of L. gibba floating on the nutrient solution could be driven by light coming from either above or below. Light from below was about 75% as effective as from above when the stand was sparse, but much less so with dense stands. High rates of photosynthesis (ca. 800 nanomoles CO2 g dry weight (DW)-1 s-1) were measured at 750 micromoles m-2 s-1 PPF and 1500 micromoles mol-1 CO2. This was attained at densities up to 660 g fresh weight (FW) m-2 with young cultures. After a few days growth under these conditions, and at higher densities, the rate of photosynthesis dropped to less than 25% of the initial value. This drop was only partly alleviated by thinning the stand or by introducing a short dark period at high temperature (26 degrees C). Despite the drop in the rate of photosynthesis, maximum yields were obtained in batch cultures grown under continuous light, constant temperature and high [CO2]. Plant protein content was less than reported for field grown Lemna. When the plants were harvested daily, maintaining a stand density of 600 g FW m-2, yields of 18 g DW m-2 d-1 were obtained. The total dry weight of L. gibba included 40% soluble material (sugars and amino acids), 15% protein, 5% starch, 5% ash and 35% cellulose and other polymers. We conclude that a CELSS system could be designed around stacked, alternate layers of transparent Lemna trays and lamps. This would allow for 7 tiers per meter height. Based on present data from single layers, the yield of such a system is calculated to be 135 g DW m-3 d-1 of a 100% edible, protein-rich food.

Carbon↗

Cross-reactivity of antibody against an epitope of the Plasmodium falciparum second merozoite surface antigen.

Monoclonal antibodies directed against the 51 kD merozoite surface antigen of Plasmodium falciparum also bind to other antigens within the infected cell. The sizes of these cross-reacting antigens have been characterized. Immunofluorescence due to the reaction of one of the monoclonal antibodies with these cross-reacting antigens was localized in the intra-erythrocytic parasite and in granules in the infected red cell cytoplasm. This immunofluorescence could be distinguished from the merozoite surface antigen in parasite lines with a variant serotype of the merozoite surface antigen which fails to react with the monoclonal antibodies. It was found that the in-vitro growth inhibition caused by the presence of one of the monoclonal antibodies, 8G10/48, was dependent on the expression of the corresponding serotype of merozoite surface antigen, a finding consistent with the inhibitory effect of this antibody being primarily directed against the merozoite surface antigen and not the cross-reacting antigens. Analysis of the frequency at which epitopes occur suggests that such cross-reacting proteins will be commonly seen in malaria, without the need to postulate a selective advantage for such cross-reacting specificities.

Animals↗

[Reduction of renal reperfusion damage following warm ischemia by allopurinol and superoxide dismutase].

Preserved organs are damaged not only by the ischemic injury due to lack of oxygen. The reperfusion injury mediated by oxygen free radicals is an important factor in the postischemic organ failure. The prevention of free radical-induced reperfusion injury with allopurinol (AP) and superoxide dismutase (SOD) is shown in a warm ischemia kidney model. Rats were treated with allopurinol (40 mg/kg i.v.) one hour, or with SOD (20,000 IU/kg i.v.) one minute before reperfusion after a period of 35 minutes of warm ischemia. Allopurinol and SOD reduced significantly the postischemic kidney failure with a less important increase of creatinine. Creatinine levels on day three in the control group: 517 +/- 87 mumol/ml, in the SOD-group: 206 +/- 105 mumol/ml, and in the AP-group: 163 +/- 81 mumol/ml (anal. of variance: p = 0.0001). AP has a wide therapeutic range. We feel, that it is important to confirm the prevention of reperfusion injury by allopurinol prophylaxis clinically.

Allopurinol↗

Sexual abuse in young children: its clinical presentation and characteristic patterns.

A retrospective record survey was performed using all child clients aged less than 7 years seen at a community mental health center during the period 1982-1984. The total number of 202 children fell into three groups: sexually abused (n = 37), physically abused (n = 35), and nonabused clinical children (n = 130). These groups were compared in order to learn more about sexual abuse in young children. Family background of both abused groups were similar to each other but differed from the nonabused group in having more factors related to family stress than the nonabused group. Clinical presentations of all the children overlapped a great deal symptomatically; however, the sexually abused children had a statistically significant higher frequency of inappropriate sexual behavior than the other two groups. Several characteristics of the abusive patterns suffered by the two abuse groups differed at or near statistical significance: sexually abused children were more often victimized in single acts by nonrelated child perpetrators than were physically abused children.

Adaptation, Psychological↗

Development and evaluation of modifications to the Sickness Impact Profile for head injury.

Three modifications were made to the Sickness Impact Profile, a behavior-based measure of health status, to improve its sensitivity to the effects of head injury. (1) Additional items were included to capture head injury sequelae and behaviors typical of young adults, the age group to which head injury most frequently occurs. (2) Subjects individually excluded behaviors irrelevant to them, thus allowing the score to better reflect injury-related changes. (3) The different areas of functioning on the Sickness Impact Profile were reweighted to reflect global judgments of the construct's contribution to overall functioning rather than the sum of the item contributions. Only the first modification is head-injury specific. The others, are relevant to any disease or injury. The performance of the modifications was evaluated in a longitudinal study of 102 head injured and 102 comparison subjects tested at 1 and 12 months after injury. The evaluation of the modifications was based on their ability to distinguish head injury from comparison subjects and on the strength of their relationship with measures of brain dysfunction. Despite a few statistically significant improvements in discrimination, differences of a practical degree were not obtained. The standard Sickness Impact Profile performed well and is recommended for evaluation of day-to-day functioning in head injury studies.

Activities of Daily Living↗

Failure of Chlamydia trachomatis to pass transplacentally to fetuses of TO mice infected during pregnancy.

Mice (strain TO) were inoculated with a human strain of Chlamydia trachomatis (serovar E) either 14 days before the detection of a vaginal plug (day 1 of pregnancy), or from one to nine days thereafter. The organisms were given via the intraperitoneal route (ip) or intravenously with an additional intravaginal inoculum (iv + ivag). Mice were killed on day 18 of pregnancy and the contents of the uterus examined. Chlamydiae were isolated from at least one placental disk of about a quarter of the mice. Organisms given via the ip route established placental colonisation more effectively. Thus, placental colonisation was detected in five of 16 mice given chlamydiae by the ip route (in six of eight placentas in one mouse), whereas colonisation occurred in only a single placenta from one of nine mice infected via the iv + ivag routes. Chlamydiae were isolated from 13 (6.25%) of 208 placentas examined; the degree of colonisation was variable and the individual placentas were colonised independently. Chlamydiae were not recovered from fetal tissue, even when there was heavy placental colonisation. Nor were they isolated from maternal spleens, even though there was antibody to C. trachomatis in all maternal sera; the titres were in the range 4-2048, depending on the time of chlamydial challenge. These experiments show that C. trachomatis did not cross the placenta and that the pregnancy outcome in these mice was not affected.

Animals↗

Infertility in mice infected genitally with a human strain of Chlamydia trachomatis.

Progesterone-treated C3H and TO mice were inoculated genitally with a human C. trachomatis strain, serovar E, designated N.I. 1 or with 2SP control medium. Of the C3H mice serving as controls 93% had litters by the end of a 6-month period compared to 31% of mice infected with chlamydiae. This infertility could not be explained by tubal occlusion, since the oviducts appeared normal at autopsy. Some of the mice were induced to superovulate. Eggs were never recovered from the oviducts on the inoculated sides of infertile mice although they were sometimes found in the lumen of the uninoculated oviducts. In contrast, eggs were recovered routinely from both oviducts of control mice. In addition, eggs and/or their accompanying cumulus cells could be seen in the periovarial space of mice inoculated with chlamydiae, indicating a failure of the transportation of eggs to the oviduct. This could explain the high incidence of ectopic pregnancies in women after chlamydial infection. No adverse effect on fertility was seen in TO mice inoculated genitally with strain N.I.1. Of the mice given 2SP medium, 73% had litters, but 87% of the mice inoculated with chlamydiae were also fertile. There was, however, a significantly greater variation in the birth weights of mice born to infected TO mothers than those born to control mice. This difference in the susceptibility of mouse strains suggests that a genetic predisposition should also be considered for man.

Animals↗

Salpingitis in mice induced by human strains of Chlamydia trachomatis.

Human strains of Chlamydia trachomatis were inoculated unilaterally into the genital tracts of female TO, CBA, CBA/nu and C3H mice via the intrauterine route or under the ovarian bursa. Inflammatory changes were not seen in the oviducts or uterus of mice given two laboratory-adapted LGV serovars (L1 and L2), although chlamydiae were recovered from the lower genital tract. However, salpingitis and endometritis occurred after each of three chlamydial strains (serovars D and E) had been inoculated. Oviduct inflammation was seen for up to 6 weeks after inoculation but reached maximum severity usually after about 2 weeks, the lumen sometimes being occluded by exudate and necrotic debris. Pathological changes were seen often in both oviducts indicating canalicular spread of the organisms through the uterus. Pre-treatment of the mice with progesterone had an enhancing effect in that the lesions developed more rapidly; such treatment, in halting the oestrous cycle, probably made a larger number of target cells available for more efficient infection. Involvement of the oviduct on the uninoculated side occurred more rapidly in T-cell impaired nude mice than in immunologically normal mice, although there was little or no effect on the severity of the oviductal changes. There was evidence that the susceptibility of different strains of mice to chlamydial salpingitis varied. Thus, inflammatory changes in C3H mice were more severe than in TO mice and the changes in C3H and CBA strains were longer lasting than those in TO mice. This suggests that a possible genetic predisposition in the human situation should not be ignored. Finally, one chlamydial strain of low passage produced more severe salpingitis in mice than another strain of similar passage. By analogy different chlamydial strains may not be of equal pathogenicity in the human situation.

Animals↗

Development of a chronic canine model for measurement of absorption by substrate appearance in portal venous blood.

Research in absorption physiology requires animal models which closely resemble the in vivo situation. The description of a new canine model satisfying these requirements is the objective of this report. Dogs were instrumented with indwelling portal vein and carotid artery catheters, a catheter jejunostomy and an electromagnetic flow measuring probe around the portal vein enabling continuous flow recordings. Following intrajejunal infusion of nutritive substrates in the conscious animal, absorption was measured as the product of porto-arterial substrate difference and portal venous flow. The model was validated in five mongrel dogs: (1) Catheters and flow measuring device function over several months. (2) The sensitivity of the method was evaluated following intrajejunal infusion of l-glycine-l-tyrosine and its constituent amino acids. A significant portoarterial concentration difference of both amino acids enabling quantitative measurement of absorption resulted when the peptide was infused at 4 mmoles/hour (20 mM solution, 200 ml/h). (3) Infusion of complete nutritive formulas caused a significant increase in portal venous flow whereas neither saline nor the amino acids or the peptides investigated had a comparable effect. (4) A validation experiment by implantation of a second flow probe distal to the chronically implanted device provided evidence that granulomatous tissue forming around the probe does not alter the accuracy of the flow recording. In summary, this method permits for the first time quantitative measurement of absorption by appearance rates in portal venous blood instead of by disappearance from the intestinal lumen.

Amino Acids↗