Biomedical subjects
Publications and source records attributed to J M Rao.
From the aerial parts of Cassia kleinii two new oxanthrone esters, kleinioxanthrone-1 and kleinioxanthrone-2 have been isolated. Their structures were established as 1,8-dihydroxy-3-methyl-6-methoxy-9(10H)-anthracenone-10-oxydecanoate 1 and 1,8-dihydroxy-3-methyl-9(10H)-anthracenone-10-oxytetradecanoate 2 respectively based on degradative and spectroscopic evidence.
An activity-directed fractionation and purification process was used to identify the antioxidant components of Cedrus deodara. Dried heartwood powder of C. deodara was first defatted with petroleum ether and then extracted with chloroform. The chloroform extract showed strong antioxidant activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. This fraction was then subjected to separation and purification using silica gel column chromatography. Three compounds with potent antioxidant activity were isolated in significant yields and identified by spectroscopic methods ((1)H NMR, (13)C NMR, IR, and MS). They were identified as (-)-matairesinol, (-)-nortrachelogenin, and a dibenzylbutyrolactollignan (4,4',9-trihydroxy-3,3'-dimethoxy-9,9'-epoxylignan). This is the first report of the occurrence of these compounds in C. deodara.
Structural and functional investigations of recombinant human hemoglobin A (HbA) isolated from the erythrocytes of transgenic swine coexpressing human alpha- and beta-globins have been carried out to authenticate its correct expression, post-translational processing and assembly. The HbA expressed in transgenic swine (TgHbA) is indistinguishable from the human-derived HbA in terms of its isoelectric pH, mass and elution pattern on a Mono S column. The chemical identity of the alpha- and beta-globin chains of TgHbA with the corresponding chains from human-derived HbA has been established by tryptic peptide mapping and amino acid sequencing. The proton NMR spectra of TgHbA have demonstrated that the conformational aspects of the protein around the heme pocket are indistinguishable from those of the control sample of HbA. The equivalence of the hydrogen bond pattern of TgHbA (in particular the inter-subunit surfaces) with that of authentic HbA has also been established by NMR studies. Consistent with these structural and conformational analyses, the TgHbA also exhibits complete functional equivalence with the human-derived HbA with respect to oxygen affinity, cooperativity, Bohr effect and allostery. Hence the studies presented here demonstrate that the transgenic swine system correctly transcribes the alpha- and beta-globin transgenes, translates the respective alpha- and beta-globin mRNA to generate the corresponding globin chains, carries out the correct cotranslational processing of the translated globin chains, inserts the heme into the globin chains in the same orientation as in the human-derived HbA and assembles the alpha- and beta-subunits into a functionally cooperative tetramer that exhibits a response to allosteric effectors identical with that of human-derived HbA. Thus, in the transgenic swine system, in vitro chemical manipulation steps such as those needed in the Escherichia coli and the yeast systems, to convert the rHbA expressed in these systems into forms functionally identical with that of the human-derived protein, are not needed. An additional advantage of the transgenic swine system is the stability of the transgenes over many generations. Hence the transgenic swine could serve as an excellent system for the production of human HbA (or its variants) for structure-function studies and for therapeutic applications.
This paper discusses a family presenting with features of Coffin-Lowry syndrome, namely abnormal facies, skeletal abnormalities and mental handicap. Two of the mildly affected females had psychotic illness with predominant depressive features, and all the severely affected males had profound sensorineural deafness.
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One hundred and twenty-nine children in the 8- to 12-year-old age group in Cardiff were ascertained to have mild mental deficiency. Detailed obstetric data were obtained which indicated that nearly 69% of the children were associated with adverse obstetric factors. Fifty-five per cent had the combined pathogenetic risk factors of pre-, peri- and neonatal adversities. Forty-two per cent of the cases had non-optimal perinatal factors and 45% were considered to have prenatal causation. There were four children with chromosomal anomalies. The various adverse obstetric influences are discussed separately.
Sixty-seven neuroleptic-mediated mentally handicapped subjects in a hospital were studied to determine the prevalence of Parkinsonian side effects. A Parkinsonism scale was devised and administered. Sixty-one per cent of the sample had mild to moderately severe side effects. Sex, age, cumulative and current chlorpromazine doses, cumulative and current anticholinergic doses and anti-epileptic medication status did not predict the Parkinsonism scores. Overt brain damage was not a predictor. The difference between the neuroleptic medicated group and neuroleptic free matched controls was highly significant indicating that the Parkinsonian type of movement disorder was related to neuroleptic medication.
A total of 117 manic-depressives who had been on lithium for a mean duration of 4.7 years were examined before lithium therapy and subsequently at intervals. Information relating to pre-lithium height and weight and current weight were determined and used to calculate the body mass index (BMI) for each individual. Other relevant variables such as age, sex, cumulative lithium dose, duration of therapy, thyroid profile and serum lithium levels were recorded. The results indicated that, although there was a nonsignificant increase in BMI for the whole population, lithium and sex were not significant predictors of any increase in BMI. In nearly 27% of patients BMI actually slightly decreased during lithium therapy. The overall conclusions from this study are that, in the population studied, lithium may not have exerted any pharmacological effects to increase BMI.
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Sixty-seven neuroleptic medicated mentally handicapped subjects in a hospital were rated on two occasions for abnormal involuntary movements on three scales: Abnormal Involuntary Movements (AIMS), Rockland and Parkinsonism scales, with 6 months between each assessment. Inter-rater and test-retest reliabilities were high. The data from the second assessment was analyzed. Prevalence of tardive dyskinesia (TD) was 21% on AIMS, 42% on the Rockland scale; 60% had parkinsonism. Multiple stepwise regression analysis revealed that age, sex, current neuroleptic and anticholinergic dose, antiepileptic medication, psychosis, cumulative anticholinergic dose were not significant predictors of TD as determined by AIMS. Parkinsonism and cumulative neuroleptic dose were significant predictors of and correlated positively with AIMS score. TD subjects formed 35% of the parkinsonian group. Overt brain damage was not a significant predictor of AIMS score and the difference between the neuroleptic medicated and neuroleptic free group on AIMS scores was highly significant.
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