Effects of cocaine on dopamine receptor gene expression: a study in the postmortem human brain

The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human.     

Inhibition of sickle beta-chain (betaS)-dependent polymerization by nonhuman alpha-chains. A superinhibitory mouse-horse chimeric alpha-chain

Horse alpha-chain inhibits sickle beta-chain-dependent polymerization; however, its inhibitory potential is not as high as that of mouse alpha-chain. Horse alpha-(1-30) and alpha-(31-141) segments make, respectively, minor and major contributions to the inhibitory potential of horse alpha-chain. The sum of the inhibitory potential of the two segments does not account for the inhibitory potential of the full-length horse alpha-chain. Although the polymerization inhibitory potential of horse alpha-chain is lower than mouse alpha-chain, the inhibitory potential of horse alpha-(31-141) is comparable to that of mouse alpha-(31-141). When mouse alpha-(1-30) is stitched to horse alpha-(31-141), the product is a chimeric alpha-chain with an inhibitory potential greater than mouse alpha-chain. In contrast, the stitching of horse alpha-(1-30) with mouse alpha-(31-141) had no additional inhibitory potential. Molecular modeling studies of HbS containing the mouse-horse chimeric alpha-chain indicate altered side-chain interactions at the alpha1beta1 interface when compared with HbS. In addition, the AB/GH corner perturbations facilitate a different stereochemistry for the interaction of the epsilon-amino group of Lys-16(alpha) with the beta-carboxyl group of Asp-116(alpha), resulting in a decrease in the accessibility of the side chain of Lys-16(alpha) to the solvent. Based on molecular modeling, we speculate that these perturbations by themselves, or in synergy with the altered conformational aspects of the alpha1beta1 interactions, represent the molecular basis of the superinhibitory potential of the mouse-horse chimeric alpha-chains.     

Integrated radiation hybrid and yeast artificial chromosome map of chromosome 9p

OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.     

Preoperative sonographic diagnosis of acute appendicitis caused by Ascaris lumbricoides

Acute appendicitis caused by Ascaris lumbricoides is an uncommon variant of a common disease. We describe a case in which sonography was used for preoperative diagnosis of ascaris appendicitis.     

Abdominal tuberculosis: a presumptive diagnosis

BACKGROUND: Abdominal tuberculosis (TB) is common. But the diagnosis of abdominal TB is fraught with difficulties as it is often not possible to get a microbiological confirmation of the infection. We therefore undertook this study to highlight those pertinent clinical and laboratory features which would enable one to make a provisional diagnosis of abdominal TB early, to pave way for a trial of anti-tuberculosis chemotherapy. METHOD: This is a retrospective study of 12 patients treated for abdominal TB in our department over a period of 2 years. FINDINGS: Seven of the patients suffered from chronic diarrhoea for periods ranging from 4 weeks to 12 months. Four patients had progressive abdominal distension (ascites). The last patient came in with multiple abdominal swellings. Seven patients had clinical and biochemical features of malabsorption. Another 9 patients also had persistent pyrexia. The ascitic fluid was exudative in the 4 patients mentioned earlier. A definitive diagnosis could not be established in any of these patients. The diagnosis of abdominal TB was thus one of exclusion in these patients who showed prompt response to anti-tuberculosis therapy. CONCLUSION: Our study justifies a trial of anti-TB chemotherapy in TB endemic areas in the following clinical situations: (a) patients with chronic diarrhoea of unknown aetiology and (b) patients with exudative ascitic fluid, after all other possible causes, have been excluded. A prompt response to anti-TB therapy should be accepted as sufficient ground for the diagnosis of abdominal TB even when histopathological or microbiological confirmation of the disease is not possible. Our study reflects the experience of other workers from Third World countries.     

Adenosine in the mammalian heart: nothing to get excited about

Until quite recently, the cardiodepressant actions of adenosine were widely accepted. A nucleoside that produces negative chronotropic and ionotropic effects, adenosine, has been used clinically as the drug of choice for terminating supraventricular (atrioventricular node) tachycardia and is likely to play an important part in regulating arrhythmogenic activity as an endogenous antiarrhythmic metabolite. Despite this, recent experimental data, particularly resulting from in vitro studies using animal models, have shown a paradoxical excitable action of adenosine in the heart. In this article, Amir Pelleg and Steven Kutalek present the reasons why they continue to believe that any excitatory actions of adenosine in the heart are clinically irrelevant.