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Biomedical subjects

A Majid

Publications and source records attributed to A Majid.

At least 37 records · Page 2Linked to original sources

Genetic linkage study of a major susceptibility locus (D2S125) in a British population of non-insulin dependent diabetic sib-pairs using a simple non-isotopic screening method.

A polymorphic microsatellite marker (D2S125) was recently reported to show significant linkage to non-insulin dependent diabetes mellitus (NIDDM) in a population of Mexican-American affected sib-pairs. We have used a simple non-isotopic screening technique employing the polymerase chain reaction (PCR) with a biotinylated primer to study the genetic linkage and allele frequency distribution of the D2S125 marker in a population of 109 British NIDDMs (62 possible affected sib-pairs). The analysis provided no evidence for linkage of the D2S125 marker in the British subjects (MLS = 0.029, P > 0.05). The PCR screening method used proved to be a convenient and reliable alternative to the radiolabelling of PCR products.

Diabetes Mellitus, Type 2↗

Rheumatoid factor idiotypic and antigenic specificity is strongly influenced by the light chain VJ junction.

The aim of this study was to define the structural basis for rheumatoid factor (RF) specificity and for the expression of the RF light chain-associated Ids, 4C9 and 6B6.6, by determining the reactivity of recombined heavy and light chains of Ig derived from monoclonal B cell lines of patients with rheumatoid arthritis and of light chains with site-directed mutations. We found that expression of the 4C9 and 6B6.6 Ids resulted from use of the VkIIIa genes Humkv 328 and Vg, but only in the presence of a permissive VJ junction. Expression of the Ids was independent of heavy chain use for the Humkv328-encoded light chains, but was highly dependent on the associated heavy chain for the Vg-encoded light chains. The RF specificity of the Abs was primarily heavy chain dependent, but the light chain VJ junction was critical in determining the relative avidity of the Abs for Fc. Our study points to the critical contribution of the somatically generated VJ junction to RF autoantibody specificity and to the expression of the two RF-associated Ids studied.

Amino Acid Sequence↗

Risks for transmission of hepatitis C virus during artificial insemination.

OBJECTIVE: To identify risks of hepatitis C virus transmission by semen from infected donors. DESIGN: Case report. SETTING: Assisted fertility clinic. PATIENTS: Hepatitis C virus-infected semen donor and recipients of his donations. INTERVENTION: Testing for hepatitis C virus by serology and polymerase chain reaction. MAIN OUTCOME MEASURES: Detection of hepatitis C virus antibodies and viral RNA. RESULTS: Hepatitis C virus RNA was detected in the semen donation before but not after purification; none of the recipients of the donors samples were found to have antibodies to hepatitis C virus. CONCLUSIONS: Hepatitis C virus RNA can be detected in semen donations from infected donors; purification of donations before insemination significantly reduces the amount of viral RNA in the semen pellet.

Antibodies, Viral↗

Effects of tiagabine and vigabatrin on GABA uptake into primary cultures of rat cortical astrocytes.

Tiagabine (TGB) and vigabatrin (VGB) are two novel anticonvulsant compounds reported to exert their pharmacological effects via an action on the gamma-aminobutyric acid (GABA) system. We have investigated the effects of acute exposure of these drugs on the uptake of GABA into rat cortical astrocytes in primary culture. Astrocytes were prepared from the cerebral cortices of one day-old rat pups by a mechanical dissociation technique and were assayed for GABA uptake activity after 21 days in culture. Tiagabine (100-300 nM) and VGB (100 microM) reduced GABA uptake when compared to control at four hours post-exposure. GABA uptake was also reduced following eight and 24 hour exposures to 200 nM TGB. A combination of TGB (200 nM) and VGB (100 microM) treatments reduced GABA uptake when compared to both control and VGB treated cultures. These results support the efficacy of TGB as a GABA uptake inhibitor and suggest that VGB may also exert an effect by this mechanism.

Animals↗

The order of draw of blood specimens into additive containing tubes not affect potassium and calcium measurements.

The effect of order of draw when taking blood into tubes containing additive was investigated in 47 medical inpatients; 12 of these patients acted as a control group. The samples were analysed in the order in which they were withdrawn. The results of potassium and calcium concentrations did not differ significantly between groups. Manufacturers recommend a specific order of draw when taking blood using vacuum based blood collection systems, which are routinely used in many hospitals. The results of this study, however, show that order of draw has no effect on calcium or potassium concentrations.

Blood Specimen Collection↗

Molecular scanning of candidate mitochondrial tRNA genes in type 2 (non-insulin dependent) diabetes mellitus.

Mitochondrial DNA (mtDNA) gene defects may play a role in the development of non-insulin dependent diabetes mellitus (NIDDM). In order to search for potentially diabetogenic mtDNA defects we have applied the technique of single stranded conformational polymorphism (SSCP) analysis to 124 patients with a history of NIDDM and 40 non-diabetic controls. No new heteroplasmic mutations were detected. However, a variety of homoplasmic variants were found in patients with NIDDM; some of these merit further investigation.

Base Sequence↗

Early experience of video-assisted thoracoscopic surgery.

Consecutive 25 patients (M/F:18/7) underwent video-assisted thoracoscopic surgery (VATS) for various chest illnesses. These included nine cases of pneumothorax, three cases of pericardial effusion, three cases of pleural effusion, four cases of lung lesion requiring either incisional or excisional biopsy, two cases of empyema, one case of traumatic haemothorax, and three cases of mediastinal lesion. The mean age was 36.2 years (range 19-78 years). A total of forty-three procedures were performed. The mean durations of intrapleural chest-tube requirement and hospitalisation following VATS alone were 4.5 days (range: 0-13 days) and 8.3 days (range: 2-25 days) respectively. No intraoperative complication and VATS procedure-related mortality reported. Apart from simple analgesics such as paracetamol or tramadolol, no opiate analgesia was given to patients undergoing only VATS. The results support that VATS is a safe and effective procedure in the management of pulmonary, mediastinal, pericardial and pleural diseases and the treatment of persistent and recurrent spontaneous pneumothorax.

Adult↗

Hyperplasia of thymic gland.

Hyperplasia of the thymus is the most common anterior mediastinal mass in infants. It is however exceedingly difficult to evaluate by the weight of the gland as it continues to grow after birth until puberty and thereafter undergoes progressive atrophy. It normally maintains most of the radiographic characteristics of the normal thymus. Massive thymic hyperplasia, a rare variant of true thymic hyperplasia is extremely rare during the first two decades of life and clinically can cause mediastinal compression or acute and recurrent pulmonary infection. Two such cases are reported and the clinico-pathology is briefly described and discussed.

Diagnosis, Differential↗

Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities.

The prevalence of hepatitis C virus (HCV) infection amongst a group of intravenous drug users (IVDUs) resident in West Suffolk (East Anglia, England) was investigated and compared with the prevalence of infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV). In addition, both the level of HCV persistence, as defined by detection of viral RNA, and the HCV genotypes present in this population were determined. It was found that HCV antibodies were present in 59% of those tested; by comparison 22% had antibodies to HBV and 1% antibodies to HIV. HCV RNA was found in 44% of those with HCV antibody. HCV genotype 1 was the most prevalent within this population although both genotypes 2 and 3 were also represented.

Adolescent↗

Mitochondrial gene defects in patients with NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) has a strong genetic component and maternal factors have recently been implicated in disease inheritance. The mitochondrial myopathies are a group of diseases which often show maternal inheritance as a result of mtDNA defects; some patients have impaired glucose tolerance. Occasional families with maternally inherited diabetes and deafness associated with a deletion or point mutation of mtDNA have been reported. To assess the importance of mitochondrial gene defects in NIDDM, 150 unrelated diabetic subjects from Wales, UK and 68 unrelated patients with diabetes and at least one affected sibling from England, UK were studied. Southern blot analysis did not show any large mtDNA deletions or duplications. One patient had a mutation in the mitochondrial tRNAleu(UUR) gene at bp 3243. This mutation is commonly associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS). Study of this patient and his siblings showed a distinct form of late-onset diabetes associated with nerve deafness but no clinical features of the MELAS syndrome. No diabetic subject was shown to have the mtDNA mutation at position 8344 (tRNA(lys)) which has previously been described in the syndrome of mitochondrial encephalomyopathy and red-ragged fibres (MERRF). The role of other mitochondrial gene defects in diabetes and the pathophysiological basis of glucose intolerance in patients with the MELAS mutation requires further elucidation.

Base Sequence↗

Involvement of alpha 1-adrenoceptors in the depolarizing but not the hyperpolarizing responses of motorneurones in the neonate rat to noradrenaline.

Superfusion of the hemisected lumbar spinal cord in the neonate rat with solutions containing 10(-6) to 10(-3) M noradrenaline (NA), elicited graded depolarizations recorded from ventral roots, with a mean EC50 value of 15.1 +/- 1.5 microM (mean +/- SEM, n = 37). Repeated concentration-response curves to NA could be determined from the same preparation. Adrenaline had a similar depolarizing action (EC50 9.9 +/- 1.7 microM, n = 11). Blockade of neuronal uptake of NA by desipramine (2 x 10(-6) M) caused some potentiation of submaximal responses to NA and shifted the EC50 to 6.0 +/- 1.7 microM (mean +/- SEM, n = 14). The depolarizing response to NA was unaffected by DL-propranolol (10(-7) M) or yohimbine (10(-7) M). Prazosin (5 x 10(-9), 10(-8) and 10(-7) M) reduced the responses and caused a progressive rightward shift of the concentration-response curve. The onset of blockade by prazosin was slow, superfusion for at least 90-120 min being required before the blockade plateaued. Prazosin (5 x 10(-9) and 10(-8) M) caused a surmountable blockade, the apparent pA2 being 8.3 +/- 0.2 (mean +/- SEM, N = 9). Depolarizations induced by NA were also antagonised by phentolamine (10(-6) M). An initial hyperpolarizing response to NA was unmasked after exposure to prazosin in 90% of preparations and was associated with a reduction in the spontaneous activity of the motorneurones. Both the hyperpolarization and reduction in spontaneous activity were attenuated by yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A double blind comparison of alprazolam, diazepam and placebo in the treatment of anxious out-patients.

The anxiolytic effects of alprazolam, a triazolobenzodiazepine, were evaluated in a double-blind 28-day comparison with diazepam and placebo in 46 out-patients suffering from anxiety states of moderate to severe intensity. Alprazolam 1.5-3 mg per day was found to be of at least equivalent anxiolytic effect to 15-30 mg diazepam per day, and there was evidence of antidepressant activity by alprazolam, but not diazepam, in neurotic depression. Side-effects occurred least often with alprazolam and were minor in nature. Laboratory data showed no changes attributable to alprazolam even in a patient who swallowed 15 capsules (7.5 mg). It was concluded that alprazolam is a safe and effective anxiolytic which is well-tolerated and also shows some antidepressant activity.

Adolescent↗