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Biomedical subjects

R Deo

Publications and source records attributed to R Deo.

7 recordsLinked to original sources

Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos.

Vitamin K-dependent carboxylase catalyzes the posttranslational modification of glutamate to gamma-carboxyglutamate (Gla) in its substrates, the vitamin K-dependent proteins (VKDPs). This modification is required for the activities of the VKDPs. Recent evidence demonstrates previously unrecognized roles for VKDPs as signaling molecules important in the regulation of cell growth, adhesion, and apoptosis, suggesting developmental functions for VKDPs and hence the carboxylase. The tissue distribution and functions of carboxylase in development are unknown. In this study, we isolated and characterized the full-length cDNA encoding the rat carboxylase and analyzed, at the cellular level, the expression of this gene in rat embryos by in situ hybridization. We demonstrate that the expression of this gene is highly regulated in a developmental and tissue-specific manner. Hepatocytes, the major site of synthesis of VKDPs of blood coagulation, express carboxylase mRNA late in gestation, in contrast to the central nervous system, mesenchymal, and skeletal tissues which express carboxylase mRNA early during rat embryogenesis. The tissue-specific temporal expression of the carboxylase gene during embryogenesis indicates that vitamin K-dependent carboxylation and the formation of Gla is developmentally regulated. These studies suggest that vitamin K-dependent carboxylation is an important modulator of embryonic VKDP function.

Amino Acid Sequence

Cloning, structural organization, and transcriptional activity of the rat vitamin K-dependent gamma-glutamyl carboxylase gene.

The vitamin K-dependent gamma-glutamyl carboxylase gene was cloned from a rat liver genomic DNA library and the structural organization of this gene was determined. The carboxylase gene is 16.3 kb in length and contains 15 exons and 14 introns. DNA sequence analysis revealed that all 14 introns were U2-Type GT-AG introns. A 2.8-kb DNA fragment corresponding to the 5'-flanking region of the cloned gene demonstrated transcriptional activity in a rat liver cell line that is known to express the endogenous carboxylase gene. DNA sequence analysis of the proximal 331 bp of this 5'-flanking sequence reveals the absence of an identifiable TATA box. Consensus sequences for several transcription factors that may be important in regulating its tissue specific expression were identified. The isolation and characterization of the rat carboxylase gene provides essential information for the analysis of its regulation in vitro and in transgenic animal models.

Animals

Osteoradionecrosis of the mandible: study of 104 cases treated by hemimandibulectomy.

One hundred and four cases of osteoradionecrosis (ORN) of the mandible following irradiation of head and neck cancer are reported. Conservative management for ORN failed in all cases. Indications of hemimandibulectomy included intractable pain, severe trismus, pathological fracture, oro-cutaneous fistula and persistent exposure of bone. Surgical approach was intra-oral in 100 cases and extra-oral in four. Immediate soft tissue reconstructions were carried out in 20 per cent cases. Post-operative complications included minor sepsis (8.6 per cent), major sepsis (2.9 per cent), haemorrhage (2.9 per cent) and fistula (3.8 per cent). Major complications occurred only in patients treated exclusively by external irradiation at doses equal to or higher than 65 Gy. Relief from pain and trismus was obtained and normal swallowing was established following radical surgery.

Adult

Remoxipride and haloperidol in the acute phase of schizophrenia: a double-blind comparison.

The efficacy and safety of remoxipride in the treatment of schizophrenia were compared with those of haloperidol in a multicentre double-blind 6-week study which was randomized with a parallel group design and was preceded by a washout period. Eighty-nine consecutively admitted men and women meeting the Research Diagnostic Criteria for schizophrenia in an acute phase of the illness were treated with remoxipride 75-300 mg twice daily or haloperidol 5-20 mg twice daily. The efficacy assessments were the Brief Psychiatric Rating Scale, Krawiecka Rating Scale, and Clinical Global Impression. Both antipsychotic drugs produced clinical improvement with no significant differences between the efficacy of the two drugs. There were relatively few side effects. There were significantly fewer extrapyramidal symptoms and instances of blurred vision with remoxipride and less constipation with haloperidol. The results indicate that remoxipride is as effective an antipsychotic as haloperidol. Remoxipride has an advantage over haloperidol in respect to extrapyramidal side effects.

Acute Disease

A comparative trial of a new antidepressant, fluoxetine.

A double-blind clinical trial was undertaken to evaluate clinical efficacy and safety of fluoxetine in comparison with the standard tricyclic antidepressant, imipramine, in the treatment of depressive illness. The opportunity was taken to compare the relationship of some standard measures of depressive illness, two observer based--Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale (Montgomery and Asberg, 1979)--and a self-rating scale--Levine Pilowsky Depression questionnaire (Pilowsky et al., 1969).

Clinical Trials as Topic

A comparative trial of a new antidepressant, fluoxetine.

This clinical trial of a new antidepressant, fluoxetine, shows it to be as effective as a standard tricyclic drug, imipramine. It is effective as a single daily dose and is free of any significant side-effects. It is less sedative and appears to cause fewer problems of weight increase. The three scales used to assess efficacy showed a very positive correlation.

Adult

Cells cultured from the diabetic (DB/DB) mouse have a permanent decrease in insulin receptors.

Investigation of mechanisms responsible for the decreased numbers of insulin receptors observed in obesity and diabetes has been facilitated by the development of cell culture systems permitting study of cellular events independent of fluctuating hormone levels and multiple endocrine interactions present in the whole organism. With such a system, we have found that cells cultured from the skin of diabetic mice have 45-48% fewer receptors for insulin than those from nondiabetic littermates. This difference is maintained in culture over many generations, suggesting that the decreased expression of insulin receptors in these cells is related to the genetic trait for diabetes.

Animals