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Biomedical subjects

S Joshi

Publications and source records attributed to S Joshi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Epidemiology of cataract in India: combating plans and strategies.

Blindness due to cataract presents an enormous problem in India not only in terms of human morbidity but also in terms of economic loss and social burden. The WHO/NPCB (National Programme for Control of Blindness) survey has shown that there is a backlog of over 22 million blind eyes (12 million blind people) in India, and 80.1% of these are blind due to cataract. The annual incidence of cataract blindness is about 3.8 million. The present annual level of performance is in the order of about 1.6-1.9 million cataract operations. To clear the backlog of cataract cases by the year 2000 and to tackle the rising incidence, 5-6 million cataract operations annually will have to be performed as against the present rate of 1. 7 million per year. India is undertaking a new long-term initiative to expand the capability of cataract surgery and service levels with financial assistance from the World Bank. An important feature of this initiative is the attention given to spread the cataract blindness programme in rural and tribal areas. The second feature is the emphasis placed on modern extracapsular cataract extraction with intra-ocular lens implantation as the preferred surgical technique. Another noteworthy feature is developing institutional capacity and appropriate co-ordination mechanisms for collaboration between the non-government organization and the public sector to expand coverage to the most disadvantaged populations. The fourth and the most important strategy is to carry out intensive campaigns at the state and national levels against cataract blindness in order to substantially increase the demand for cataract services. A country like India has more significance for such a plan in view of the fact that various social, economic and environmental factors contribute to cataract blindness in populations at a much younger age.

Blindness↗
PubMed1999

Amino acids and peptides. LIV. Application of 2-adamantyl derivatives as protecting groups to the synthesis of peptide fragments related to Sulfolobus solifataricus ribonuclease. I.

The 2-adamantyloxycarbonyl group was employed for the protection of the epsilon-amino group of Lys and the hydroxyl group of Tyr, and the 2-adamantyl ester was employed for the protection of the beta-carboxyl group of Asp in order to construct eight peptide segments as building blocks for the preparation of peptide fragments related to the sequence of Sulfolobus solifataricus Ribonuclease. The usefulness of the above protecting groups developed in our laboratory was confirmed.

Adamantane↗
PubMed1999

Amino acids and peptides. LV. Application of 2-adamantyl derivatives as protecting groups to the synthesis of peptide fragments related to Sulfolobus solifataricus ribonuclease. II.

Segment condensations were performed to construct peptide fragments related to Sulfolobus solifataricus Ribonuclease. At each condensation step, the new protecting groups were stable. The protected peptide fragments were treated with a low-high HF procedure to give the desired peptide fragments. These peptide fragments were also prepared by the solid-phase method, and the obtained peptides were compared with those obtained by the solution method. The peptide fragments obtained by the solution method were identical with those obtained by the solid-phase method on analytical HPLC, indicating that the new protecting groups could be easily removed by HF, and no racemization occurred during the synthesis of the protected peptides.

Adamantane↗
PubMed1999

RNA-polymerase III-driven expression cassettes in human gene therapy.

tRNAs, U6 small nuclear RNA and adenovirus virus associated RNAs are transcribed by RNA polymerase III. These RNAs are expressed in high levels and possess increased stability due to their small, compact size. Promoters expressing these RNAs have therefore been used to express a variety of interfering RNAs, including ribozymes, antisense RNAs and sense or decoy RNAs. Intracellular expression and activity of RNA polymerase III-driven interfering RNAs have been demonstrated in several studies. This review will summarize the design and application of RNA polymerase III-driven expression cassettes in human gene therapy using retroviral vectors as the primary method of gene delivery.

Gene Expression↗
PubMed1999

Biotinidase deficiency: a treatable genetic disorder in the Saudi population.

Biotinidase deficiency is an autosomal recessive genetic disorder which is not uncommon in the Saudi population. Biotinidase is responsible for biotin recycling and biotin is an essential cofactor for activation of the carboxylase enzymes. Absence of biotinidase leads to infantile or early childhood encephalopathy, seizure disorder, dermatitis, alopecia, neural deafness and optic atrophy. The disease can be diagnosed by simple fluorometric enzyme assay. Treatment with biotin is both cheap and simple, resulting in rewarding clinical recovery and normalization of the biochemical, neuroradiological and neurophysiological parameters. If neglected, however, a patient may die of acute metabolic acidosis or may suffer from permanent neural deafness and optic atrophy, with mental and motor handicap. We describe the detection and treatment of 20 cases of biotinidase deficiency in our hospital and recommend the introduction of a neonatal screening programme for this disorder.

Amidohydrolases↗
PubMed1998

Dietary phytoestrogens and their role in hormonally dependent disease.

Epidemiological studies suggest that diets rich in phytoestrogens (plant estrogens), particularly soy and unrefined grain products, may be associated with low risk of breast and prostate cancer. It has also been proposed that dietary phytoestrogens could play a role in the prevention of other estrogen-related conditions, namely cardiovascular disease, menopausal symptoms and post-menopausal osteoporosis. However, there is no direct evidence for the beneficial effects of phytoestrogens in humans. All information is based on consumption of phytoestrogen-rich diets, and the causal relationship and the mechanisms of phytoestrogen action in humans still remain to be demonstrated. In addition, the possible adverse effects of phytoestrogens have not been evaluated. It is plausible that phytoestrogens, as any exogenous hormonally active agent, might also cause adverse effects in the endocrine system, i.e. act as endocrine disrupters.

Animals↗
PubMed1998

Cytogenetic studies in patients from India with T-acute lymphoblastic leukemia.

Cytogenetic analysis was performed in 30 patients with T cell acute lymphoblastic leukemia (11 adults, 19 children) at initial presentation and analysis was also repeated in clinical and hematological remission in 15 patients. At initial presentation, chromosomal abnormalities were detected in 27 cases (90%) and hypodiploidy was detected in 19 patients (63.3%), followed by pseudodiploidy in six patients (20%) and hyperdiploidy in two patients (6.6%). Other karyotypic abnormalities detected were deletion 6q (40%), deletion 11 q (16.6%), deletion 7q (10%), abnormalities of chromosome 9 in (13.3%) and translocation t(11;14)(p13;q11) in 6.6% and der(12)t(12;?)(p13;?) in (3.3%). In complete remission, nine out of 15 cases (60%) showed chromosomal aberrations. Original abnormalities were detected in two cases (13.3%) and new abnormalities were detected in seven cases (46.6%).

Adolescent↗
PubMed1998

Genistein exerts estrogen-like effects in male mouse reproductive tract.

The aim of this study was to evaluate the estrogenicity of genistein in the neonatal and adult male mouse reproductive tract. In intact adults, genistein (2.5 mg s.c./kg of body weight/day for 9 days) reduced testicular and serum testosterone concentrations, pituitary LH-content and prostate weight. In castrated adults, genistein (0.025-2.5 mg s.c./kg of body weight) increased expression of c-fos gene in prostatic urethra. In adult, neonatally estrogenized mice showing an increased estrogen sensitivity, a 10-day treatment with genistein (2.5 mg s.c./kg of body weight) induced development of squamous epithelial metaplasia in prostatic collecting ducts. Neonatally, only a very high dose of genistein (1 mg/pup per day; i.e. approximately 500 mg/kg of body weight) induced persistent structural changes, similar to those seen in mice treated neonatally with diethylstilbestrol, in the urethroprostatic complex. These results suggest that in adult males, genistein induces the typical estrogenic effects in doses comparable to those present in soy-based diets, while in neonatal animals, considerably higher doses are required to show estrogen-like activity.

Aging↗
PubMed1998

Hippocampal morphometry in schizophrenia by high dimensional brain mapping.

Theories of the pathophysiology of schizophrenia have implicated the hippocampus, but controversy remains regarding hippocampal abnormalities in patients with schizophrenia. In vivo studies of hippocampal anatomy using high resolution magnetic resonance scanning and manual methods for volumetric measurement have yielded inconclusive results, perhaps because of the normal variability in hippocampal volume and the error involved in manual measurement techniques. To resolve this controversy, high dimensional transformations of a computerized brain template were used to compare hippocampal volumes and shape characteristics in 15 matched pairs of schizophrenia and control subjects. The transformations were derived from principles of general pattern matching and were constrained according to the physical properties of fluids. The analysis and comparison of hippocampal shapes based on these transformations were far superior to the comparison of hippocampal volumes or other global indices of hippocampal anatomy in showing a statistically significant difference between the two groups. In the schizophrenia subjects, hippocampal shape deformations were found to be localized to subregions of the structure that send projections to prefrontal cortex. The results of this study demonstrate that abnormalities of hippocampal anatomy occur in schizophrenia and support current hypotheses that schizophrenia involves a disturbance of hippocampal-prefrontal connections. These results also show that comparisons of neuroanatomical shapes can be more informative than volume comparisons for identifying individuals with neuropsychiatric diseases, such as schizophrenia.

Brain Mapping↗
PubMed1998

Co-packaging of sense and antisense RNAs: a novel strategy for blocking HIV-1 replication.

Retroviral vectors were engineered to express either sense (MoTiN-TRPsie+) or sense and antisense (MoTN-TRPsie+/-) RNAs containing the human immunodeficiency virus type-1 (HIV-1) trans -activation response (TAR) element and the extended packaging (Psie) signal. The Psie signal includes the dimer linkage structure (DLS) and the Rev response element (RRE). Amphotropic vector particles were used to transduce a human CD4+ T-lymphoid (MT4) cell line. Stable transductants were then tested for sense and antisense RNA production and susceptibility to HIV-1 infection. HIV-1 production was significantly decreased in cells transduced with MoTiN-TRPsie+ and MoTN-TRPsie+/-vectors. Efficient packaging of sense and most remarkably of antisense RNA was observed within the virus progeny. Infectivity of this virus was significantly decreased in both cases, suggesting that the interfering RNAs were co-packaged with HIV-1 RNA. Vector transduction was not expected to occur and was not observed. Inhibition of HIV-1 replication was also demonstrated in human peripheral blood lymphocytes transduced with retroviral vectors expressing antisense RNA. These results suggest that (i) both sense and antisense RNAs were co-packaged with HIV-1 RNA, (ii) the co-packaged sense and antisense RNAs inhibited virus infectivity and (iii) the co-packaged sense and antisense RNAs were not transduced. Sense and antisense RNA-based strategies may also be used to co-package other interfering RNAs (e.g. ribozymes) to cleave HIV-1 virion RNA.

Base Sequence↗
PubMed1998

Functional and structural mapping of human cerebral cortex: solutions are in the surfaces.

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.

Anatomy, Cross-Sectional↗
PubMed1998

Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in glutaric aciduria type 1: clinical and MRI correlations.

The clinical, PET (positron emission tomography) and MRI (magnetic resonance imaging) findings of brain studies in eight patients, previously diagnosed to have glutaric aciduria type 1, were retrospectively reviewed. The neurological findings typically consisted of variable degrees of dementia and extrapyramidal symptoms (dystonia, choreoathetosis and rigidity). Both MRI and PET showed involvement of the putamina in all the patients. The PET scan demonstrated lesions in the head of the caudate nuclei in all of the patients. Brain atrophy, and in particular the characteristically-enlarged Sylvian fissures, was better demonstrated by MRI. On the other hand, the cerebral cortex and thalamic structures were found to be normal by MRI in all patients, whereas PET scan showed decreased uptake in the cerebral cortex in seven, and in the thalami in three patients. Correlation between imaging and clinical findings was found to be good when both PET scan and MRI findings of the brain were taken into consideration. Therefore, the functional (PET) and structural (MRI) studies of the brain were complementary in the imaging evaluation of glutaric aciduria type 1.

Brain↗
PubMed1998

Theoretical modelling of arteriovenous malformation rupture risk: a feasibility and validation study.

PURPOSE: To explore the feasibility of using a theoretical computational model to simulate the risk of spontaneous arteriovenous malformation (AVM) haemorrhage. METHODS: Data from 12 patients were collected from a prospective databank which documented the angioarchitecture and morphological characteristics of the AVM and the feeding mean arterial pressure (FMAP) measured during initial superselective angiography prior to any treatment. Using the data, a computational model of the cerebral circulation and the AVM was constructed for each patient (patient-specific model). Two model risk (Risk(model)) calculations (haemodynamic- and structural-weighted estimates) were performed by using the patient-specific models. In our previously developed method of haemodynamic-weighted estimate, Risk(model) was calculated with the simulated intranidal pressures related to its maximal and minimal values. In the method of structural-weighted estimate developed and described in this paper, the vessel mechanical properties and probability calculation were considered in more detail than in the haemodynamic-weighted estimate. Risk(model) was then compared to experimentally determined risk which was calculated using a statistical method for determining the relative risk of having initially presented with AVM haemorrhage, termed Risk(exp). RESULTS: The Risk(model) calculated by both haemodynamic- and structural-weighted estimates correlated with experimental risks with chi2 = 6.0 and 0.64, respectively. The risks of the structural-weighted estimate were more correlated to experimental risks. CONCLUSIONS: Using two different approaches to the calculation of AVM haemorrhage risk, we found a general agreement with independent statistical estimates of haemorrhagic risk based on patient data. Computational approaches are feasible; future work can focus on specific pathomechanistic questions. Detailed patient-specific computational models can also be developed as an adjunct to individual patient risk assessment for risk-stratification purposes.

Cerebral Hemorrhage↗
PubMed1998

Successful management of concurrent congenital dyserythropoietic anaemia and autoimmune haemolytic anaemia with splenectomy.

This first known case of concurrent congenital dyserythropoietic anaemia (CDA) and autoimmune haemolytic anaemia (AIHA) which occurred in a hispanic male and spanned 6 years from the age of 2. Light and electron microscopy of bone marrow erythroblasts and immunophenotyping confirmed CDA; serum/eluate warm autoantibodies and positive direct antiglobulin tests (DAT) associated with severe, episodic anaemias established AIHA. Cytogenetic analysis of bone marrow cells and peripheral blood lymphocytes ascertained sex chromosome aneuploidy (48 XY,+ Y,+ Y). Recurrent, life-threatening episodes of transfusion-dependent anaemia refractory to steroids and intravenous immune globulin, were put into stable remission at age 8 years when splenectomy successfully managed both disorders.

Anemia, Dyserythropoietic, Congenital↗
PubMed1998

Biotin-responsive basal ganglia disease: a novel entity.

We describe a novel, biotin-responsive basal ganglia disease in 10 patients. At onset, it appears as a subacute encephalopathy, with confusion, dysarthria and dysphagia with occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progresses to severe cogwheel rigidity, dystonia and quadriparesis. These symptoms disappear within a few days if biotin (5-10 mg/kg/day) is administered, and there are no neurological sequelae. They reappear within 1 month if biotin is discontinued. Patients diagnosed late, or who have had repeated episodes, suffer from residual symptoms such as paraparesis, mild mental retardation or dystonia. The numerous biochemical studies of intermediary metabolism, like the autoimmune and toxicological studies, enzyme assays including biotinidase, carboxylase and lysosomal activities, and bacterial and viral studies were all normal. The aetiology may be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiological abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This was present during the initial acute encephalopathy and remained unchanged during follow-up of 3-10 years. Although its aetiology is unknown, it is important to recognize this disease, since its symptoms may be reversed and the progression of its clinical course prevented simply by providing biotin.

Adolescent↗
PubMed1998

The feasibility of intracarotid adenosine for the manipulation of human cerebrovascular resistance.

UNLABELLED: To assess the feasibility of manipulating human cerebrovascular resistance with adenosine, we measured cerebral blood flow (CBF) by determining the initial slope (IS) of tracer washout 20-80 s after intracarotid 133Xe injection (standard IS) during sequential 3-min intracarotid infusions of (a) saline; (b) adenosine 1.2-mg bolus followed by an infusion of 1 mg/min (bolus + infusion); (c) saline; and (d) nicardipine (0.1 mg/min). During 133Xe washout, adenosine caused a rapidly clearing compartment. Therefore, tracer washout was also analyzed 5-25 s after injection (early IS). Nicardipine (n = 8) increased both standard IS (from 39+/-12 to 53+/-16 mL 100g.min(-1); P < 0.005) and early IS (from 40+/-9 to 55+/-20 arbitrary units; P < 0.02) to a similar degree. Adenosine bolus + infusion increased early IS (from 33+/-6 to 82+/-43 arbitrary units; P < 0.02) but did not increase standard IS (from 41+/-12 to 43 +/-16 mL 100g(-1) min(-1)). Standard and early IS values were then determined before and after adenosine delivered either by infusion alone (2 mg/min for 3 min, n = 5) or bolus alone (2 mg in 1 s, n = 3). Neither standard nor early IS changed after adenosine infusion alone. Early IS increased after adenosine bolus alone. Increase in early IS, but not standard IS, suggests a transient (<30 s) increase in CBF. IMPLICATIONS: Intracarotid adenosine, in the 1- to 2-mg dose range, may cause a transient, but not a sustained, increase in cerebral blood flow. Intracarotid adenosine in such a dose range does not seem to be an appropriate drug for sustained manipulation of cerebrovascular resistance.

Adenosine↗