Biomedical subjects
Publications and source records attributed to G Kumar.
The HIV protease inhibitor ABT-378 (Lopinavir) is metabolized rapidly and extensively by CYP-3A4 catalyzed oxidation. Three of the major metabolites identified were synthesized and their antiviral (HIV) activities determined.
Muscarinic acetylcholine receptors (mAChRs) can be differentially localized in polarized cells. To identify potential sorting signals that mediate mAChR targeting, we examined the sorting of mAChRs in Madin-Darby canine kidney cells, a widely used model system. Expression of FLAG-tagged mAChRs in polarized Madin-Darby canine kidney cells demonstrated that the M(2) subtype is sorted apically, whereas M(3) is targeted basolaterally. Expression of M(2)/M(3) receptor chimeras revealed that a 21-residue sequence, Ser(271)-Ser(291), from the M(3) third intracellular loop contains a basolateral sorting signal. Substitution of sequences containing the M(3) sorting signal into the homologous regions of M(2) was sufficient to confer basolateral localization to this apical receptor. Sequences containing the M(3) sorting signal also conferred basolateral targeting to M(2) when added to either the third intracellular loop or the C-terminal cytoplasmic tail. Furthermore, addition of a sequence containing the M(3) basolateral sorting signal to the cytoplasmic tail of the interleukin-2 receptor alpha-chain caused significant basolateral targeting of this heterologous apical protein. The results indicate that the M(3) basolateral sorting signal is dominant over apical signals in M(2) and acts in a position-independent manner. The M(3) sorting signal represents a novel basolateral targeting motif for G protein-coupled receptors.
Brown-Sequard syndrome (BSS) is a unilateral cord injury characterised by an ipsilateral motor deficit with contralateral pain and temperature hypoaesthesia. Although there are a variety of causes, the majority of cases are generally of neoplastic origin or are traumatic in origin. We describe a rare cause of Brown-Sequard syndrome as a result of post-traumatic arachnoiditis. Magnetic resonance imaging with the use of thin-slice high-resolution constructive interference in steady state (CISS) and T2-weighted spin-echo sequence were used to demonstrate the cause and appearance of the lesion in the spinal canal and was useful in the assessment and management of the patient. This case illustrates the usefulness of the CISS sequence in MRI for elucidating arachnoiditis.
Asian Indians are at high risk for the development of atherosclerosis and related complications, possibly initiated by higher body fat (BF). The present study attempted to establish appropriate cut-off levels of the BMI for defining overweight, considering percentage BF in healthy Asian Indians in northern India as the standard. A total of 123 healthy volunteers (eighty-six males aged 18--75 years and thirty-seven females aged 20--69 years) participated in the study. Clinical examination and anthropometric measurements were performed, and percentage BF was calculated. BMI for males was 21.4 (sd 3.7) kg/m(2) and for females was 23.3 (sd 5.5) kg/m(2). Percentage BF was 21.3 (sd 7.6) in males and 35.4 (sd 5.0) in females. A comparison of BF data among Caucasians, Blacks, Polynesians and Asian ethnic groups (e.g. immigrant Chinese) revealed conspicuous differences. Receiver operating characteristic (ROC) curve analysis showed a low sensitivity and negative predictive value of the conventional cut-off value of the BMI (25 kg/m(2)) in identifying subjects with overweight as compared to the cut-off value based on percentage BF (males >25, females >30). This observation is particularly obvious in females, resulting in substantial misclassification. Based on the ROC curve, a lower cut-off value of the BMI (21.5 kg/m(2) for males and 19.0 kg/m(2) for females) displayed the optimal sensitivity and specificity, and less misclassification in identification of subjects with high percentage BF. Furthermore, a novel obesity variable, BF:BMI, was tested and should prove useful for interethnic comparison of body composition. In the northern Indian population, the conventional cut-off level of the BMI underestimates overweight and obesity when percentage BF is used as the standard to define overweight. These preliminary findings, if confirmed in a larger number of subjects and with the use of instruments having a higher accuracy of BF assessment, would be crucial for planning and the prevention and treatment of various obesity-related metabolic diseases in the Asian Indian population.
Explore the source record for details and available documents.
The mood modules from the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Patient Health Questionnaire (PHQ) were administered to 17 (52%) female and 16 (48%) male adolescent (13-17 years old) psychiatric inpatients. The internal consistencies of both were good (KR-20 for PRIME-MD=.80, Cronbach coefficient alpha for Patient Health Questionnaire=.85). The correlation between the PRIME-MD and Patient Health Questionnaire total scores was .87 (p<.001), and the point-biserial correlation of both questionnaires' total scores with being diagnosed with a Major Depressive Disorder was .54 (p<.001). Both mood modules appeared to be equally effective in screening for a Major Depressive Disorder.
To provide further information about the construct validities of the Beck Youth Inventories of Emotional and Social Impairment, these inventories were administered to 35 female and 65 male outpatients whose ages ranged from 7 to 12 years and who were diagnosed with various psychiatric disorders. The Children's Depression Inventory was also administered, and the children were rated by a parent with the Conners' Parent Rating Scale-Revised: Short Form. The scores on the former inventory were more positively correlated with the scores on the Beck Youth Depression Inventory (r =.81, p<.001) than with scores on the four other Beck Youth Inventories, and those on the Conners Oppositional scale were comparably correlated with the scores on the Beck Youth Disruptive Behavior (r=.49, p<.001) and Anger (r=.41, p<.001) Inventories. These latter correlations were higher than those for scores on the Oppositional scale with the scores on the three other Beck scales.
INTRODUCTION: Although the majority of patients with primary hyperparathyroidism have a relatively asymptomatic benign disorder, there are patients who have a more aggressive disorder. CLINICAL PICTURE: We report a case of primary hyperparathyroidism presenting during pregnancy complicated by antepartum haemorrhage and severe prematurity. The diagnosis was made postpartum, when her problems rapidly progressed to result in severe neuromuscular weakness, bilateral pathological hip fractures as well as nephrolithiasis. TREATMENT: Surgical parathyroidectomy was performed. The underlying lesion was a large solitary parathyroid adenoma with cystic elements. CONCLUSION: Primary hyperparathyroidism is not an innocuous disease and can result in severe morbidity if left untreated.
Explore the source record for details and available documents.
An enzymatic method to graft hexyloxyphenol onto the biopolymer chitosan was studied. The method employs tyrosinase to convert the phenol into a reactive o-quinone, which undergoes subsequent nonenzymatic reaction with chitosan. Reactions were conducted under heterogeneous conditions using chitosan films and also under homogeneous conditions using aqueous methanolic mixtures capable of dissolving both hexyloxyphenol and chitosan. Tyrosinase was shown to catalyze the oxidation of hexyloxyphenol in such aqueous methanolic solutions. Chemical evidence for covalent grafting onto chitosan was provided by three independent spectroscopic approaches. Specifically, enzymatic modification resulted in (1) the appearance of broad absorbance in the 350-nm region of the UV/vis spectra for chitosan films; (2) changes in the NH bending and stretching regions of chitosan's IR spectra; and (3) a base-soluble material with (1)H-NMR signals characteristic of both chitosan and the alkyl groups of hexyloxyphenol. Hexyloxyphenol modification resulted in dramatic changes in chitosan's functional properties. On the basis of contact angle measurements, heterogeneous modification of a chitosan film yielded a hydrophobic surface. Homogeneously modified chitosan offered rheological properties characteristic of associating water-soluble polymers.
India currently has an infant mortality rate (IMR) of 73 and aims to reach 60 per 1000 live births by 2000 A.D. The "at risk" approach which has been traditionally used for Maternal and Child Health services could help to reduce costs. The main objective of the study was to identity socio-demographic "risk factors" at family level for underfive deaths and assess the validity and efficiency of a risk index scale for this purpose. A computerised database on about 71,000 individuals in 28 villages in Ballabgarh Block exists since 1987. All the underfive deaths in the study area during the period 1991-95 were compared with age and sex matched controls on socio-demographic variables. All variables which were found significant at 10% level were taken in for logistic regression. The variables found significant were used to construct a ten point scale. This scaling system was applied to all the families with an underfive child during the two year period 1996-97. Validity and efficiency of this approach was calculated. A total of 849 cases and their age and sex matched controls were studied. The variables which were significantly associated with risk of underfive deaths were: not received measles vaccine (2.19; 1.58-3.04), history of sibling death (2.03; 1.19-3.45), maternal illiteracy (1.86; 1.23-2.81), never used a contraceptive (1.59; 1.17-2.14), having more than 4 children (1.46; 1.04-2.05). About 40% of houses were labelled as high risk. The sensitivity and specificity were around 60%. The improvement in efficiency by the risk approach was 33%. Risk approach is helpful in identifying families who are at greater risk of having underfive deaths. It results in a modest increase in the efficiency of services.
Using analogies from nature, we investigated the possibility that tyrosinase-catalyzed reactions of 3,4-dihydroxyphenethylamine (dopamine) could confer water-resistant adhesive properties to semidilute solutions of the polysaccharide chitosan. Rheological measurements showed that the tyrosinase-catalyzed, and subsequent uncatalyzed, reactions lead to substantial increases in the viscosity of the chitosan solutions. Samples from these high-viscosity modified-chitosans were spread onto dry glass slides, the slides were lapped and clipped together either in air or after being submerged in water, and the bound slides were held under water for several hours. Adhesive shear strengths of over 400 kPa were observed for these modified chitosan samples, while control chitosan solutions conferred no adhesive strength (i.e., the glass slides separated in the absence of measurable forces). High viscosities and water-resistant adhesive strengths were also observed when semidilute chitosan solutions were treated with the known cross-linking agent, glutaraldehyde. Further studies indicate a relationship between the increased viscosities and water-resistant adhesion. These results demonstrate that the renewable biopolymer chitosan can be converted into a water-resistant adhesive.
BACKGROUND: India aims to reduce the infant mortality rate (IMR) to below 60 per 1000 live births by 2000. IMR is higher in northern India as compared with south Indian states like Kerala. Any further reduction in IMR needs identification of new strategies. The Ballabgarh project with an IMR of 36 in 1997 can help identify such strategies. OBJECTIVE: To see the trend in reduction of neonatal mortality rate (NNMR) and IMR at the Ballabgarh project, compare it with Kerala and rural India's trend and look at the causes of neonatal and infant mortality. DESIGN: The Comprehensive Rural Health Services Project, Ballabgarh, run by the All India Institute of Medical Sciences, covered an estimated population of 70,079 in 1997. The health care delivery system is on the national pattern. All the deaths are identified during the house visits by the male workers. The cause of death is ascertained by the health assistant based on the symptomatology at the time of death. RESULTS: The trends in reduction of IMR for Ballabgarh, Kerala and rural India are roughly parallel with the IMR of Ballabgarh lying somewhere in between the two. However, the NNMR of Ballabgarh (10.6 in 1996) was comparable to Kerala's NNMR (10.9 in 1992). The proportion of infant deaths occurring during the neonatal period had fallen from 50% in the early seventies to 30% during 1996-97. In 1992-1994, 33.8% of all neonatal deaths were attributable to low birth weight and 37.3% to infective causes. Acute respiratory infection and diarrhoea continue to be the chief cause of postneonatal mortality. CONCLUSION: It is possible to bring down neonatal mortality before postneonatal mortality. The Kerala model, which focuses on social development, may not apply to northern India for sociocultural reasons.
To identify novel potassium channel genes expressed in the retina, we screened a human retina cDNA library with an EST sequence showing partial homology to inwardly rectifying potassium (Kir) channel genes. The isolated cDNA yielded a 2,961-base pair sequence with the predicted open reading frame showing strong homology to the rat Kir2. 4 (rKir2.4). Northern analysis of mRNA from human and bovine tissues showed preferential expression of Kir2.4 in the neural retina. In situ hybridization to sections of monkey retina detected Kir2.4 transcript in most retinal neurons. Somatic hybridization analysis and dual-color in situ hybridization to metaphase chromosomes mapped Kir2.4 to human chromosome 19 q13.1-q13.3. Expression of human Kir2. 4 cRNA in Xenopus oocytes generated strong, inwardly rectifying K(+) currents that were enhanced by extracellular alkalinization. We conclude that human Kir2.4 encodes an inwardly rectifying K(+) channel that is preferentially expressed in the neural retina and that is sensitive to physiological changes in extracellular pH.
Explore the source record for details and available documents.
Lipoleiomyoma is a very uncommon tumor, and broad ligament of uterus is one of the rare sites. No case has been reported in last five years. This case is presented because of its rarity and its uncommon site of occurrence.
Chitosan is a natural biopolymer whose rich amine functionality confers water solubility at low pH. At higher pH's (greater than 6. 5), the amines are deprotonated and chitosan is insoluble. To attain water solubility under basic conditions we enzymatically grafted the hydrophilic compound chlorogenic acid onto chitosan. Despite its name, chlorogenic acid is a nonchlorinated phenolic natural product that has carboxylic acid and hydroxyl functionality. The enzyme in this study was tyrosinase, which converts a wide range of phenolic substrates into electrophilic o-quinones. The o-quinones are freely diffusible and can undergo reaction with the nucleophilic amino groups of chitosan. Using slightly acidic conditions (pH = 6), it was possible to modify chitosan under homogeneous conditions. When the amount of chlorogenic acid used in the modification reaction exceeded 30% relative to chitosan's amino groups, the modified chitosan was observed to be soluble under both acidic and basic conditions, and to have a pH window of insolubility at near neutral pH. 1H NMR spectra confirmed that chitosan was chemically modified, although the degree of modification was low. Copyright 1999 John Wiley & Sons, Inc.
BACKGROUND: When residents complete their pediatric training, patients from their continuity practices in academic settings must be reassigned to either a known resident of their selection or an unknown, incoming intern. OBJECTIVES: To determine what antecedent factors were associated with patient reassignment to a known resident of their selection, whether such reassignment was associated with increased health care use, and what factors were associated with continuity with the new resident provider. DESIGN: Nonconcurrent cohort study. SETTING: Hospital-based resident continuity clinic practice. PARTICIPANTS: Patients of residents graduating in June 1993. RESULTS: Seven hundred fifty-eight patients of 18 graduating residents required reassignment: 86 patients (11%) were assigned to a resident colleague, defined as the study group. From the remaining 673 patients who were assigned to unknown, incoming interns, a control group was randomly selected (n = 160), with approximately 2 patients for each study group subject. Looking at antecedent factors, study group patients were more likely to have chronic medical problems and to have seen their graduating resident more often and more recently. Univariate analysis explored the consequent factors of health care use and found that study group patients were more likely to return for a visit and to make more visits with the new provider. Multiple logistic regression analysis demonstrated that being in the study group, younger age at the original encounter with the graduating resident, and a shorter interval since the last visit with the graduating resident were all associated with increased continuity with the new resident. CONCLUSIONS: The method of patient reassignment at a continuity clinic was associated with chronic disease of the patient and regularity of visits with the graduating resident. Increased continuity with a new resident, as determined by multivariate analysis, was associated with the method of reassignment, a younger age at first encounter with the graduating resident, and a shorter interval since the last visit with the graduating resident. This study has implications at ambulatory sites where transitions occur.