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Biomedical subjects

A Agrawal

Publications and source records attributed to A Agrawal.

At least 127 records · Page 7Linked to original sources

Vitiligo: surgical repigmentation of leukotrichia.

BACKGROUND: Patients with vitiligo frequently have premature gray hair. Until recently the literature was silent about its management. While surgically treating vitiligo, we incidentally observed repigmentation of gray hair. OBJECTIVE: Based on our observations we undertook this study to see the effect of surgical treatment of vitiligo on repigmentation of leukotrichia, as well as to evaluate the percentage of repigmentation, if any, in the different hair-bearing areas, and the time taken for it. METHODS: A case series of eight patients with nine patches of localized, stable, and refractory vitiligo with leukotrichia of 3-12 years duration is presented. The patients were followed up for 2-6 years. One patient was lost from follow-up after 2 months. The vitiligo was treated by dermabrasion and thin split-thickness skin grafting under local anesthesia, as outpatients. RESULTS: Repigmentation of the hair occurred in all the areas but it was seen earlier (3 months) and was more complete in the eyebrows (70-95%). In the scalp and the beard areas it started later (6-9 months) and was around 50-60% only. The degree of pigmentation increased until about 3 years after surgery. No complications in the form of graft loss or alopecia were observed. CONCLUSIONS: Partial to near-total repigmentation of leukotrichia can be achieved surgically. Contrary to the present theory, we hypothesize that melanocytes also migrate from the repigmented epidermis to the hair follicle, resulting in repigmentation of the hair.

Adolescent↗

A double blind placebo controlled trial of ginkgo biloba extract in acute cerebral ischaemia.

A double blind placebo controlled trial was conducted in 55 patients of acute ischaemic stroke. Twenty one and twenty six patients were randomly allotted in group A and group B respectively. In group A, the patients received 40 mg Ginkgo biloba extract at 6 hourly intervals along with routine management. The placebo tablets were dispensed in the tablet form of same size, shape and colour and were given in the same way. After the patients were subjected to computerized tomographic (CT) scan to confirm acute ischaemic infarction, they were assessed on Mathew's scale and reassessed, at 2 weeks and 4 weeks of drug/placebo administration. Both groups showed significant improvement in Mathew's scale score after 2 weeks and 4 weeks. The difference in degree of change was negligible (p > 0.05) in either group. Estimation of relative changes of neurological deficit based on baseline values also showed negligible (p > 0.05) difference. A trial of Ginkgo biloba extract within 6 hours of stroke in a larger dose and in larger sample could be beneficial clinically in patients of cerebral ischaemic infarct, and needs further study. The usefulness of the plant extract has been demonstrated clinically and experimentally in more than 40 trials of chronic cerebral ischaemia, done elsewhere. This was not evident in our study as our study group was different (more than 48 hours after stroke). There appears to be no contraindication or adverse effect of this medication (Ginkgo biloba) in acute ischaemic stroke.

Brain Ischemia↗

Probing the C1q-binding site on human C-reactive protein by site-directed mutagenesis.

We have used oligonucleotide-directed site-specific mutagenesis to investigate structural determinants of the C1q-binding site of C-reactive protein (CRP). Eleven mutant rCRP cDNAs, D112N; D112A; D112K; D112E; K114T; K114A; K114E; K114R; R116L; D112N, K114T; and D112N, R116L were constructed and expressed in COS cells. Wild-type (wt) and all mutant rCRPs bound to phosphocholine-substituted BSA and also to pneumococcal C-polysaccharide with apparent avidities similar to native CRP, except for the R116L mutant which bound slightly less avidly. Substitution of Asn, Ala, or Lys for Asp-112 resulted in decreased avidity of ligand-bound CRP for C1q and also in decreased C-activating efficiency as estimated from a C3-fragment deposition assay. However, complexes of the D112E mutant reproducibly bound better to C1q and activated the classical pathway more efficiently than wt rCRP. Substitution of Thr, Ala, or Glu for Lys-114 increased the avidity for C1q by 2- to 3-fold and the efficiency of classical pathway activation by 20- to 30-fold compared with wt CRP. In contrast, the K114R mutant was only slightly different from wt CRP. Substitution of Leu for Arg-116 did not significantly affect C1q-binding but resulted in increased C-activating efficiency. The data indicate that the negative charge of residue Asp-112 plays a major role in the formation of the C1q-binding site of CRP and that the positively-charged residue Lys-114 and to a lesser extent also Arg-116 play important but indirect roles in C1q-binding and activation of C by CRP complexes.

Amino Acid Sequence↗

Intraorbital extraocular tuberculosis: a report of three cases.

Intraorbital extraocular tuberculosis is a rare disease. We have recently treated three cases with a good outcome. This article discusses the clinical radiologic and operative features that we encountered. Tuberculosis disease should be considered as one of the differential diagnosis of intraorbital extraocular space-occupying lesions in India.

Adolescent↗

Repeated haloperidol increases both calmodulin and a calmodulin-binding protein in rat striatum.

Repeated treatment with the antipsychotic drug, haloperidol, leads to an increased behavioral sensitivity to dopamine agonists exhibited upon withdrawal from the drug. An increase in the particulate content of the endogenous Ca(2+)-binding protein, calmodulin, has been demonstrated after repeated treatment of rats with haloperidol. In this study, the anatomical specificity of the effect of repeated haloperidol treatment on the content and subcellular localization of calmodulin was investigated. Responsivity of calmodulin localization to dopaminergic input following drug treatment was assessed by determining the subcellular localization of calmodulin following an in vivo amphetamine challenge before sacrifice. Male, Sprague-Dawley rats were treated with 0.5 mg/kg haloperidol (s.c.) for 3 weeks and withdrawn from the drug for 4 days. Repeated haloperidol increased calmodulin content only in the striatum but altered the subcellular distribution of calmodulin in rat limbic forebrain and frontal cortex. In the latter areas, the soluble calmodulin was increased while the particulate calmodulin was decreased. There was no change in calmodulin in either hippocampus or cerebellum in response to drug treatment. Challenge with the dopamine mimetic, amphetamine, before sacrifice was effective in redistributing calmodulin only in striatum from rats that had been treated repeatedly with haloperidol, demonstrating an increased sensitivity of the translocation process. In order to determine whether a change in a calmodulin-binding protein would accompany the drug-induced increase in calmodulin, striatal calmodulin-binding proteins were examined using a biotinylated calmodulin overlay technique. Repeated haloperidol treatment enhanced calmodulin binding to a 150 kDa protein in striatal membranes. The 150 kDa protein exhibited the same gel mobility and subcellular distribution as myosin light chain kinase immunoreactivity. There was an increase in myosin light chain kinase immunoreactivity in striatal membranes after repeated haloperidol that was apparent in animals withdrawn either 4 or 10 days from haloperidol treatment. Therefore, repeated haloperidol could increase the rat striatal content of calmodulin and potentially that of the calmodulin-binding protein, myosin light chain kinase. Increases in striatal calmodulin and myosin light chain kinase may signal a greatly enhanced sensitivity of actin-myosin interactions after repeated haloperidol that could contribute to haloperidol-induced neurochemical or morphological changes involved in drug-induced synaptic plasticity.

Amphetamine↗

Effect of oral theophylline on resting energy expenditure in normal volunteers.

BACKGROUND: The aim of this study was to investigate the contribution of regular treatment with oral theophylline to the increase in resting oxygen consumption observed in patients with chronic airflow limitation who are receiving bronchodilator therapy. METHODS: Resting oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 10 normal subjects (six men, age 21-48 years, weight 50-85 kg) before and after 11 days of treatment with either placebo or theophylline in a double blind manner, in twice daily oral doses ensuring trough serum concentrations between 8.4 and 13.5 mg/l. An open canopy method was used to measure VO2 and VCO2 and in all test conditions this was extended for 60 minutes after an inhalation of 800 micrograms of salbutamol super-imposed on the background placebo or theophylline treatment. RESULTS: Resting VO2 and heart rate were increased during theophylline treatment compared with placebo by 6.5% and 8.4% respectively. Salbutamol inhalation transiently increased VO2, VCO2, and heart rate in all tests but this was not modified by background theophylline treatment. CONCLUSION: Oral theophylline treatment causes a sustained increase in resting oxygen consumption and heart rate but does not modify the metabolic response to acutely inhaled salbutamol.

Adult↗

Congenital malformations at birth.

Three thousand nine hundred and thirty-two consecutive newborns were examined at birth for the presence of congenital malformations. The overall incidence of malformations was 1.2%. Congenital malformations accounted for 9.2% of perinatal and 12.8% of neonatal deaths. The central nervous system (39.5%) was most commonly involved followed by musculoskeletal system (14.5%). Involvement of more than one system was observed in 18.8% cases. Though there was higher incidence of malformations in babies born to mothers of more than 35 years the difference was not statistically significant. However, the babies born to mothers of gravidity 4 or more had significantly higher incidence of malformation when compared to mothers of lower gravidity (chi1(2) = 4.67, p < 0.05). The incidence of congenital malformations at birth was higher in stillborn and low birthweight babies.

Abnormalities, Multiple↗

Audit in maternal and child health.

Audit in medicine is a well tried means of assessing the quality of practice by using acceptable measures of outcome. Audit in maternal and child health has been limited to fatal outcomes such as maternal and perinatal deaths. The outcome of audit is of interest to the providers, the health authorities and the consumers. The utility of audit lies in effective use of data to improve quality of service. Quality control of instruments and education of junior staff are some other benefits of audit. The limitations of manpower, money, means, fear of litigation and above all dislike of clinicians for handling data are hurdles in the way of effective audit. The concept of 'Standard Primipara' and 'Total Fetal Wastage' are likely to add new dimension to perinatal audit.

Child Health Services↗

Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors.

The efficacy and cytotoxic properties of immunotoxin conjugates directed against the transferrin receptor were examined in cell lines and operative specimens from pediatric brain tumors. Dose-response relationships were assessed for immunotoxin-mediated inhibition of protein synthesis for two immunotoxins, 454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell line exhibited similar sensitivity to both immunotoxins with IC50s in the 10(-9)-10(-10) M range. The time course of protein synthesis inhibition by the immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain tumors was also examined. The more aggressive and malignant tumor types such as glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), indicating that these tumors were extremely sensitive to transferrin receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and benign tumors was not as greatly affected by immunotoxins. Immunoblots showed expression of transferrin receptors on the cell lines and tumors which correlated with in vitro sensitivity to immunotoxin. The results demonstrate that two immunotoxins targeted to the transferrin receptor are efficacious in killing brain tumor cell lines and primary tumor cultures at very low concentrations and that highly malignant tumors are especially sensitive to this cytotoxic response.

Brain Neoplasms↗

Praziquantel therapy in neurocysticercosis.

Neurocysticercosis is being recognised more often now, because of advances in radio-imaging. No treatment was available for this disease till about a decade back. Praziquantel has provided new hope. From India, there are very few published reports on experience with this drug. Nine cases of neurocysticercosis are being presented, where praziquantel therapy has been tried. Five patients with tumour syndrome and one patient with a meningoencephalitic syndrome have shown a favourable response. In 3 patients with epilepsy syndrome, it is difficult to assess the role of this drug in their management. The relevant data have been presented and analysed.

Adolescent↗

Probing the phosphocholine-binding site of human C-reactive protein by site-directed mutagenesis.

Human C-reactive protein (CRP) can activate the classical pathway of complement and function as an opsonin only when it is complexed to an appropriate ligand. Most known CRP ligands bind to the phosphocholine (PCh)-binding site of the protein. In the present study, we used oligonucleotide-directed site-specific mutagenesis to investigate structural determinants of the PCh-binding site of CRP. Eight mutant recombinant (r) CRP, Y40F; E42Q; Y40F, E42Q; K57Q; R58G; K57Q, R58G; W67K; and K57Q, R58G, W67K were constructed and expressed in COS cells. Wild-type and all mutant rCRP except for the W67K mutants bound to solid-phase PCh-substituted bovine serum albumin (PCh-BSA) with similar apparent avidities. However, W67K rCRP had decreased avidity for PCh-BSA and the triple mutant, K57Q, R58G, W67K, failed to bind PCh-BSA. Inhibition experiments using PCh and dAMP as inhibitors indicated that both Lys-57 and Arg-58 contribute to PCh binding. They also indicated that Trp-67 provides interactions with the choline group. The Y40F and E42Q mutants were found to have increased avidity for fibronectin compared to wild-type rCRP. We conclude that the residues Lys-57, Arg-58, and Trp-67 contribute to the structure of the PCh-binding site of human CRP. Residues Tyr-40 and Glu-42 do not appear to participate in the formation of the PCh-binding site of CRP, however, they may be located in the vicinity of the fibronectin-binding site of CRP.

Amino Acid Sequence↗

Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG.

In this paper, we demonstrate the synthesis of the complement component C2 and factors B and D by the human astroglioma cell line U105-MG. All three components were structurally and antigenically similar to their serum counterparts, as determined by biosynthetic labelling studies or Western blot analysis. Northern blot analysis demonstrated that the mRNAs of all three components had the same apparent sizes as the equivalent mRNAs from hepatocyte and monocyte cell lines. Interestingly, U105-MG cells produce two C2 transcripts with sizes of approximately 2.8 and 2.3 kb. Interferon-gamma (IFN-gamma) enhanced the expression of C2 and factor B mRNA and protein in a dose- and time-dependent fashion, while factor D expression was refractory to IFN-gamma. IFN-gamma appeared to predominantly enhance the expression of the large (2.8 kb) C2 transcript. Kinetic studies demonstrated peak C2 and factor B expression in 48 h in response to IFN-gamma, similar to the acute-phase response of factor B in serum. These data are the first to demonstrate the synthesis of C2 and factor D by astroglioma cells. Combined with previous reports documenting the synthesis of C3 by astrocytes, our data suggest that endogenous synthesis of complement proteins, and particularly of alternative pathway activation components (C3, factors B and D), may play an important role in host defence in the central nervous system.

Astrocytoma↗