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Biomedical subjects

D J Martin

Publications and source records attributed to D J Martin.

At least 109 records · Page 6Linked to original sources

Novel recombinations of the IG kappa-locus that result in allelic exclusion.

Allelic exclusion of Ig H and L chain gene loci serves to ensure that a B cell expresses a single specificity antibody. The analysis of Abelson murine leukemia virus transformed cells that rearrange the kappa-locus during growth in cell culture has provided the opportunity to characterize intermediate steps in Ig gene rearrangement. By sequential cloning of an Abelson murine leukemia virus transformed cell line we have observed a novel two-step pathway that results in a rearrangement of a V kappa gene segment into the J-C kappa intron. This type of rearrangement effectively excludes functional kappa expression from that allele. A truncated mRNA product resulting from the V kappa signal exon splicing to the C kappa exon is diagnostic of these unique rearrangements. In addition to demonstrating a novel mechanism for allelic exclusion, the two-step pathway described serves to explain how V-intron recombination products were generated in previously described cell lines.

Alleles↗

Considerations on the further expansion of the AIDS epidemic in South Africa--1990.

An epidemiological composite of the human immunodeficiency virus (HIV) epidemic in South Africa was constructed from reported acquired immunodeficiency syndrome (AIDS) figures, blood donor seroprevalence data and a family of active surveillance studies in the Johannesburg area. Of great concern is the extensive and continuing silent spread of HIV in the urban black population, manifested by doubling times in male and female sexually transmitted disease (STD) clinic attenders of 10.67 and 9.78 months respectively, a doubling time in female family planning (FP) attenders of 6.55 months, and HIV infection rates of 1:56, 1:37 and 1:91, respectively. These data suggest a spread of infection far more extensive than the relatively lower AIDS figures. However, seroprevalence figures in municipal employees of mainly rural origin were considerably lower, only 1:1,250 in black men and none in women, but regular movements between urban and rural areas could well introduce and amplify infection in rural areas. A complete epidemiological picture of HIV can only be attained by employing both the above approach of the family of surveys complemented by a nationwide seroprevalence study to assess HIV penetration into the general 'background' population. Educational interventions should now be particularly targeted to the major risk groups in the urban black heterosexual community.

Acquired Immunodeficiency Syndrome↗

The frequency of multiple recombination events occurring at the human Ig kappa L chain locus.

Products of Ig kappa L chain gene rearrangement in a variety of human B cell samples were investigated by sequential Southern blot hybridization analysis. By application of four region-specific probes (C kappa, J kappa, U' kappa and kappa de) a complete spectrum of kappa rearrangements, including both predicted and novel products, were detected. Nearly 30% of the products detected reflect multiple recombination of the kappa locus. The kappa-deleting element was responsible for 70% of the multiple rearrangements that were detected. Interestingly, eight kappa-expressing samples exhibited rearrangement of the kappa-deleting element. The remaining multiple recombination products were characteristic of double V kappa-J kappa rearrangement. This frequency reveals that secondary V-J rearrangement may significantly contribute to the expression of kappa L chains in humans.

Alleles↗

Ultrasonography in the management of possible appendicitis in childhood.

One hundred thirty-four children referred to the pediatric surgical service with the diagnosis of possible acute appendicitis underwent abdominal ultrasonography within 24 hours of admission. A final diagnosis of appendicitis was made in 45, and of gynecological disease in 11 children. One child had pancreatitis, another jejunal perforation, and a third gross mesenteric lymphadenopathy. In 75 children the clinical picture completely resolved without a definitive diagnosis being made. Clinical diagnosis of gynecological disease showed two false-negatives, and three false-positives, whereas the ultrasonographic diagnosis was accurate in all patients. The sensitivity of the pediatric surgical diagnosis at the time of admission for acute appendicitis was 49% (23 false-negatives) and the specificity was 95% (three false-positives). Ultrasonographic diagnosis of appendicitis had a sensitivity of 89% (five false-negatives) and a specificity of 92% (five false-positives). There was a negative laparotomy rate of 0.7% (one patient) using both clinical evaluation and ultrasonography. These data suggest that abdominal ultrasonography in the child with possible appendicitis is an important diagnostic adjunct.

Abdominal Pain↗

Pulmonary and systemic haemodynamic effects of cromakalim in conditions of normoxia and hypoxia in dogs.

1. In anaesthetized-closed chest dogs, exposure to hypoxia (60 min) caused a sustained increase in arterial pulmonary pressures (diastolic: DPP, mean: MPP and effective capillary: EPCP by 132, 66 and 104% respectively) and increased total pulmonary vascular resistance (TPVR, 143%) with minimal changes in systemic haemodynamics. 2. Under normoxia, cromakalim infusion (2 micrograms kg-1 min-1 for 30 min) progressively decreased diastolic systemic arterial pressure (DBP, 30%) and total systemic vascular resistance (TSVR, 54%). In contrast, DPP was increased by 45%, due to an increase in cardiac output (CO: 55%), while TPVR was essentially unchanged. 3. Under hypoxic conditions, cromakalim (2 micrograms kg-1 min-1 for 30 min) induced changes in systemic haemodynamics comparable to those seen under normoxia. However, DPP was decreased by 37% at the end of infusion. The compound progressively decreased TPVR in a dose-related manner and PaO2 (55.9 mmHg) was maintained since cardiac output was increased. 4. Thus, under normoxia, cromakalim induced haemodynamic effects on the pulmonary circulation which were directly related to an increase in CO, but were clearly different from those observed under hypoxia. In the hypoxia-induced constricted pulmonary vascular bed, cromakalim effectively reduced the elevated pulmonary vascular resistance at low doses but showed comparable vasodilator effects on the systemic circulation under both conditions. The findings suggest that a vasodilator agent like cromakalim may be useful in patients with respiratory conditions associated with elevated pulmonary vascular resistance.

Animals↗

Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells.

The splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from splicing of the previously characterized 8.4-kb germ line transcript, while a 0.8-kb mRNA was the splice product of a second 4.7-kb germ line transcript that initiated 50 base pairs upstream of J kappa 1. The interaction of the two kappa germ line promoters with nuclear binding factors is also examined. The potential role of these germ line transcripts in establishing the rearrangement potential of the locus is discussed.

Animals↗

Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting beta 1-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized study, involving four match-pair trials (placebo versus esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures, 160). We administered a 4-min infusion of either placebo or esmolol at the rate of 500 micrograms.kg-1.min-1. We then induced anesthesia with methohexital and succinylcholine. After administration of electrical stimulation for ECT, the rate of infusion decreased to 300 micrograms.kg-1.min-1 for three additional minutes and was then discontinued. Statistically significant reductions in mean heart rate from minute 2 until minute 15 and in maximum heart rate (the mean of each patient's maximum heart rate after seizure changed from 152 +/- 23 to 115 +/- 24 beats/min) occurred in patients given esmolol. During and immediately after infusion, arterial blood pressure also decreased. Finally, the length of seizures decreased, as manifested clinically from 48 +/- 18 to 39 +/- 14 s and on electroencephalogram from 86 +/- 41 to 67 +/- 28 s. We conclude that esmolol effectively controls the hyperdynamic response to ECT and reduces the length of seizures. The significance of the latter to the overall effectiveness of ECT is not known.

Adrenergic beta-Antagonists↗

Ultrasonographic studies in the management of recurrent abdominal pain.

The medical records of 65 children and adolescents who had abdominal ultrasonography for the evaluation of recurrent abdominal pain were reviewed. Fifty-three subjects (81%) had normal results; in 12 cases (19%) an abnormality was detected. In no case could the pain be attributed to the abnormal finding. Furthermore, in 3 subjects, disclosure of the abnormal findings could have caused more harm than good. The role of the abdominal ultrasonographic study in the management of recurrent abdominal pain in children and adolescents is discussed.

Abdomen↗

AIDS clinic--a year on.

In March 1987 a clinic under the auspices of the South African Medical Research Council's AIDS Research Unit was established. In the first year of its existence certain issues were identified. These are discussed and a model for future clinics is proposed.

Acquired Immunodeficiency Syndrome↗

Neuroendocrine aspects of primary endogenous depression. V. Serum prolactin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of prolactin (PRL) secretion in endogenous depression, we determined nocturnal serum PRL concentrations and PRL responses to thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (LHRH), and dexamethasone administration in 40 Research Diagnostic Criteria (RDC) primary, definite endogenous depressives and 40 individually matched normal control subjects. Compared to their matched controls, the patients showed no difference in basal nocturnal PRL concentrations, a marginally significant 20%-25% increase in the PRL response to TRH, and no differences in post-LHRH or postdexamethasone PRL concentrations. In the patients, there was a weak, negative correlation between age and PRL (r = -0.30), but none of the other subject characteristics or specific dimensions of depressive symptomatology were significantly related to the PRL measures. The PRL measures also were unrelated to pre- and postdexamethasone cortisol concentrations and to the thyrotropin (TSH) responses to TRH in both groups of subjects. In contrast to the previously reported hypothalamo-pituitary-adrenal cortical and thyroid axis abnormalities in these patients, our findings suggest that PRL secretion was relatively normal.

Adult↗

Event-related brain potentials in depressed patients treated with electroconvulsive therapy.

1. As impairment of attention has long been recognized as a clinical feature of depression, we undertook to evaluate in depressed subjects and controls a feature of the event-related brain potentials (ERP) the N100 wave which has been linked to attentional processes. 2. This study involved collection of EEG data in an "auditory oddball" ERP paradigm in 9 depressed subjects prior to and following a course of 6 electroconvulsive therapy (ECT) treatments, as well as 11 controls. Concurrent Hamilton depression rating scales provided a measure of symptomatic severity. 3. Pretreatment N100 amplitude was significantly lower in the depressed group while N100 latency was greater than among controls, with treatment differences from control values disappeared. Further a robust correlation (r = 0.85 p less than or equal to .0038) emerged between N100 amplitude (increased amplitude being lower) and severity of depression. 4. Those results provide evidence for a physiological attentional disturbance in depression and suggest that certain features of this disturbance relate directly to symptom severity.

Adult↗

Epidemiological considerations of the present status and future growth of the acquired immunodeficiency syndrome epidemic in South Africa.

Limited epidemiological data on acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection have been assembled by voluntarily reported AIDS figures, blood donor serum prevalence and high-risk sentinel population and random background population sero-prevalence studies. The HIV epidemic in South Africa can thus be shown to consist of four separate epidemics of which the heterosexual epidemic will undoubtedly constitute the major growth in this country. Intervention must be directed to shrinking the promiscuous core which sustains this epidemic by directing attention at female prostitution and limiting the reproductive rate of the epidemic by energetic and professionally directed education at an early stage of a child's school career. Sexually transmitted diseases will play a major role in the determination of the extent of the heterosexual epidemic.

Acquired Immunodeficiency Syndrome↗

Oxygen supplementation during electroconvulsive therapy.

The effects of ventilation with 30% and 100% oxygen were investigated on the circulatory and electrocardiographic response to electroconvulsive therapy (ECT) in 12 patients during 40 treatments. Administration of 30% oxygen resulted in a 25% decrease in seizure duration compared with 100% oxygen (P less than 0.0125). Hypoxaemia, defined as SaO2 less than 90%, occurred during five of 20 treatments with 30% oxygen and during two of 20 treatments with 100% oxygen (ns), and was associated invariably with loss of airway control. Heart rate, arterial pressure, and the incidence of cardiac arrhythmias were not affected significantly by oxygen supplementation. Inspired oxygen concentration has a significant effect on seizure activity and should be of a consistent value if a reproducible seizure is to be produced during ECT. Breathing 100% oxygen does not appear to affect adversely the cardiovascular response to ECT. However, arterial hypoxaemia may develop rapidly during or after the seizure, regardless of oxygen supplementation, if adequate control of airway and ventilation is not maintained.

Adult↗

Reabsorption kinetics of albumin from pleural space of dogs.

The reabsorption of albumin from the pleural space was measured in eight dogs receiving 0.5 ml intrapleural injection of 131I-labeled albumin and a simultaneous intravenous injection of 125I-labeled albumin. Plasma curves for both tracers were obtained over 24 h. The 125I-albumin curve served as input function of albumin for interstitial spaces, including pleura, whereas the 131I-albumin curve represented the output function from pleural space. The frequency function of albumin transit times from pleural space to plasma was obtained by deconvolution of input-output plasma curves. Plasma recovery of 131I-albumin was complete by 24 h, and the mean transit time from pleura to plasma averaged 7.95 +/- 1.57 (SD) h. Albumin reabsorption occurred mainly via lymphatics as indicated by experiments in 16 additional dogs in which their right lymph ducts or thoracic ducts were ligated before intrapleural injection. A pleural lymph flow of 0.020 +/- 0.003 (SD) ml.kg-1.h-1 was estimated, which is balanced by a comparable filtration of fluid into the pleural space. This suggests that, under physiological conditions, the subpleural lymphatics represent an important control mechanism of pleural liquid pressure.

Absorption↗

Increase in pulmonary capillary permeability in dogs exposed to 100% O2.

Changes in pulmonary capillary filtration induced by hyperoxia were investigated in 15 dogs. After 12 h of normobaric hyperoxic exposure, animals were anesthetized and artificially ventilated with 100% O2. A pulmonary lymphatic vessel was cannulated, and lymph flow and protein content were measured together with pulmonary and systemic hemodynamics. An increase in pulmonary capillary filtration was found when compared with reference data (normoxic dogs in similar conditions) gathered from available literature: lymph flow increased from 21.8 +/- 13.4 to 125.2 +/- 131.6 microliter/min, and the lymph-to-plasma protein concentration ratio increased from 0.67 +/- 0.08 to 0.78 +/- 0.08. To characterize the mechanisms involved, left atrial pressure was increased in two stages (approximately 10 and approximately 25 mmHg). The results clearly indicated an increase in pulmonary capillary permeability as evidenced by a decrease of the minimal estimate of the protein reflection coefficient from 0.62 +/- 0.05 to 0.42 +/- 0.05.

Animals↗