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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 631 records · Page 35Linked to original sources

Dynamics of conjunctival impression cytologic changes after vitamin A supplementation.

To investigate the chronological changes in conjunctival epithelium after supplementation with a massive oral dose of vitamin A, conjunctival impression cytology (CIC) with transfer was carried out repeatedly among 200 children aged 6-120 months in a randomized, double-blind, placebo-controlled study in Chandigarh (India). Significant conversion to normal CIC started 71-80 d after vitamin A supplementation and by 101-110 d conversion had taken place in all children. Compared with the placebo group, plasma retinol concentration at 100 d post-supplement was found to be significantly higher in the vitamin A-supplemented group P = 0.04. This study demonstrates that CIC responds to a massive oral dose of vitamin A 3-4 months after supplementation. These findings should guide future studies and evaluations in which CIC is used to assess response to vitamin A interventions.

Administration, Oral↗

Role of chromosome heteromorphism in early recurrent miscarriages in the Middle East.

To identify the role of chromosome polymorphism in miscarriages, an analysis was carried out on 774 couples; 391 of them with two or more miscarriages and 383 serving as control. All couples were taken from two separate ethnic groups residing in the United Arab Emirates (UAE): 199 cases and 194 controls came from the indigenous population who are UAE nationals (Arabs) whilst 192 cases and 189 controls came from the Asian expatriate population residing in the UAE (Asians). Out of 391 cases, six Arab and three Asian couples were excluded because at least one partner had a chromosomal aberration. From the control group four Arab and four Asians were excluded for similar reasons. The remaining 757 couples were analysed to detect the presence of chromosomal heteromorphism in one or both partners. The results suggest that chromosomal heteromorphism was significantly increased in the Arab study population (P < 0.05). Two heteromorphisms, 9qh and inversion (9)(p11q13) seem to be marginally related to recurrent miscarriages and only in the Arab study population. No differences were found in the distribution of chromosomal heteromorphism in couples analysed in relation to the number of miscarriages (two or more).

Journal Article↗

Expression of inflammatory cytokines by murine macrophages activated with a new synthetic lipopeptide JT3002.

The present study was undertaken to investigate the effect of JT3002, a new synthetic analogue of a lipoprotein from the outer wall of a gram-negative bacterium on the production of cytokines by mouse peritoneal macrophages. Multilamellar liposomes containing different concentrations of JT3002 induced production of the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-6 by macrophages in dose- and time-dependent manners. The presence of interferon-gamma enhanced production of tumor necrosis factor-alpha by macrophages exposed to lower concentrations of JT3002 and induced the release of nitric oxide, a potent cytolytic molecule of activated macrophages. Unlike lipopolysaccharide, JT3002 activated macrophages independently of serum, but like lipopolysaccharide, it required protein tyrosine kinase.

Animals↗

Bcl-2 deregulation leads to inhibition of sodium butyrate-induced apoptosis in human colorectal carcinoma cells.

Epidemiological studies have linked dietary fiber to the prevention of human colorectal cancer and suggest that short chain fatty acids such as butyric acid, which is produced by fermentation of dietary fiber in the large intestine, may be an important mediator of the protective effects of fiber. We investigated the role of Bcl-2 deregulation on the sensitivity of colorectal carcinoma cells to undergo butyrate-induced apoptosis. Here we report an inverse relationship between the levels of Bcl-2 and the sensitivity of colorectal carcinoma cell lines to undergo apoptosis in response to butyrate. Overexpression of Bcl-2 in colorectal carcinoma DiFi cells resulted in suppression of butyrate-induced apoptosis and enhanced cell survival in response to butyrate. Butyrate-induced apoptosis was accompanied by inhibition of expression of a 30 kDa protein (p30, immunorecognized by anti-Bcl-2 mAb) and this cellular effect of butyrate was inhibited by Bcl-2 overexpression. These findings suggest that deregulation of Bcl-2 in human colorectal carcinoma cells confers resistance to induction of apoptosis by butyrate, a dietary micronutrient.

Apoptosis↗

32P-postlabelling analysis of isomeric 7-alkylguanine adducts of styrene oxide.

Styrene 7,8-oxide, which reacts preferentially at the N-7 position of guanine, yielded two pairs of diastereomers 7-(1'-hydroxy-2'-phenylethyl)-dGMP (the alpha-isomer) and 7-(2-hydroxy-2-phenylethyl)-dGMP (the beta-isomer) on reaction with deoxyguanosine-3'-monophosphate (3'-dGMP). The alpha- and beta-isomers were formed in the ratio 32:68. T4 polynucleotide kinase preferentially mediated labelling of diastereomers corresponding to the beta-isomer. The beta-diastereomers showed a labelling efficiency of 52%, whereas the alpha-isomers showed a labelling efficiency of 4%. Molecular modelling experiments showed intrinsic differences between the two isomers. The torsion angles of C8-N7-2'-Ar and C8-N7-2'-1' for the alpha-isomers were 149.9 degrees and -26.4 degrees, whereas the torsion angles of C-8-N7-1'-2' and N7-1'-2'-Ar for the beta-isomers were 105.3 degrees and 179.4 degrees. The consequent interatomic distance between one of the hydrogens on the alpha-carbon and the 3'-phosphate group on the sugar residue was 5.3 A in the alpha-isomer whereas the closest distance between the hydrogens attached to the alpha-carbon and 3'-phosphate group in the beta-isomer was 6.2 A. This arrangement probably leads to steric overcrowding at the 3'-phosphate group in alpha-isomers and these are less efficiently phosphorylated than beta-isomers. In in vitro styrene oxide-modified salmon testis DNA alpha- and beta-isomers of 7-alkylguanines were formed in the ratio 37:63. The recovery of two diastereomeric beta-isomers in a 32P-postlabelling assay was 14%, but one of the diastereomers was obtained in 3-fold greater yield than the second isomer.

Animals↗

Rapid assessment of prevalence of cataract blindness at district level.

AIM: To find an optimal cluster size and number of clusters for a reasonable estimate of the prevalence of cataract blindness in people aged > or = 50 years in 19 rural districts of a state in India. MATERIALS: Cluster sampling methodology was used in 19 rural districts of Karnataka State, India. In each district, 15 clusters were randomly selected and 90 people aged > or = 50 years were examined in each cluster. As a result the visual acuity and lens status of a total of 22,218 people were assessed. METHODS: For each district, the design effect for cluster size ranging from 20 to 90 was calculated and the optimal cluster size and the required number of clusters to achieve an accuracy of 1% errors and 80% confidence was assessed. RESULTS: The age and gender adjusted prevalence of cataract blindness varied from 1.58% to 7.24%, which justifies district level surveys. The design effect is nearly 1.5 for clusters of sizes 30 and 40. With an average prevalence of 4.93% with 1% error and 80% confidence level, the optimal number of clusters is 37 and 28 for a cluster size of 30 and 40 respectively and the average sample size for a district around 1100. CONCLUSIONS: Rapid assessments for cataract blindness in those aged > or = 50 years can be conducted at district level in India with existing resources and at affordable costs. These provide reliable data, essential for effective monitoring and planning. Other parameters, for instance, surgical coverage can also be assessed. The availability of standardized software for data entry and analysis and strict adherence to survey procedures is essential.

Adult↗

Clinical correlates of CT abnormality in generalized childhood epilepsy in India.

The CT scan gives valuable insight into the aetiology of epilepsy. Studies done so far in India suggest that the causes are quite different from the West. CT scan has become available in larger cities in India, but is expensive. Information about clinical features that may 'predict' a CT abnormality would be useful to clinicians. The object was to determine which, if any, of 10 clinical features predict a CT abnormality in patients presenting with generalized epilepsy. Consecutive children with generalized epilepsy were enrolled prospectively and clinical features charted. Predetermined clinical variables were compared in those with and without CT abnormality. The setting was a pediatric in-patients and out-patients of a teaching hospital in northern India. One-hundred-and-sixty-two out of 178 consecutive children (age 1 month to 12 years) presenting with generalized epilepsy; ten clinical features viz seizure type, age at onset, number of seizures, duration of epilepsy, family/antecedent history, mental/neurological deficit, abnormal EEG and evidence of tuberculosis, were studied. Univariate analysis taking (1) CT abnormality/no abnormality and (2) ring/disc enhancing lesion/no such lesion on CT as outcomes. An abnormal CT scan was found in 79 (49 percent) patients. There were two high yield groups: (1) younger children with neurological/mental deficits; (2) older children without deficits. When these two groups were combined, odds ratio for CT abnormality was 3.06 (1.4-6.7). The commonest CT abnormality was a ring/disc like enhancing lesion seen in 32 patients. Higher age at onset (> 4 years), absence of mental/neurological deficits, generalized tonic-clonic type of seizures and fewer episodes of seizures at presentation were significantly associated with this finding. In addition to existing indications for CT scan, these results can guide physicians when referring patients for this investigation.

Brain↗

Factors influencing psychosocial development of preschool children in a rural area of Haryana, India.

In a cross-sectional survey, 3746 children aged less than 6 years residing in 47 randomly selected villages of district Ambala (India), were studied to find out the environmental risk factors influencing psychosocial development. A culture appropriate test battery comprising 67 test items was administered, and psychosocial development score of each child was computed by scoring each test item passed as 1 and failed as 0. At each age level children having score in lower quartile were categorised as having slow psychosocial development and those in upper quartile were labelled as having accelerated development. Logistic regression revealed that per capita income, education of mother, nutritional status of the child, number of rooms and environmental hygiene in the house, presence of a high school within easy travel distance, availability of a caretaker when mother is busy, child attending a nursery (anganwadi), households having access to newspaper, child having toys or toy substitutes, TV, books, story telling by the mother were found to have a significant association with psychosocial development of preschool children. The risk factors identified in this survey can be used for screening families at risk in rural communities and for selection of interventions for promotion of psychosocial development of children.

Analysis of Variance↗

The role of Tc-99m bone imaging in the management of pain after complicated total hip replacement.

A case of reflex sympathetic dystrophy (RSD) after total hip replacement (THR) is reported. It is a very unusual cause of pain after any arthroplasty procedure. Three-phase bone imaging diagnosed the condition and sympathetic blockade was used for confirming and treating the condition. The role of the bone scan in differentiating RSD from other causes of pain after THR is highlighted.

Ankle Joint↗

Newly diagnosed contralateral reflux after successful unilateral endoscopic correction: is it due to the pop-off mechanism?

PURPOSE: Our aim was to analyze the incidence of newly diagnosed contralateral vesicoureteral reflux after successful endoscopic correction of unilateral reflux by subureteral Teflon (polytetrafluoroethylene) injection and to explain the possible mechanisms responsible for new contralateral reflux. MATERIALS AND METHODS: A total of 1,195 children underwent successful endoscopic correction of high grade primary and duplex grades III to V vesicoureteral reflux by subureteral polytetrafluoroethylene injection. Unilateral and bilateral reflux was noted in 495 and 700 children, respectively. The 495 cases of unilateral reflux were retrospectively analyzed for new contralateral reflux. Voiding cystourethrography was performed in all cases 3 months and 1 year after injection. RESULTS: New contralateral reflux was diagnosed in 37 children (7%), including reflux in a single system in 33 and into a lower pole of a completely duplicated system in 4. There was no correlation of grade of ipsilateral reflux with the subsequent development of new contralateral reflux. No abnormality of the contralateral ureteral orifice was identified at initial cystoscopy, except for laterally placed ureteral orifices in 2 patients. CONCLUSIONS: The low incidence of new contralateral vesicoureteral reflux diagnosed after subureteral polytetrafluoroethylene injection versus open ureteral reimplantation may be due to noninterference with the contralateral trigone in endoscopic correction. The risk of new contralateral reflux did not increase with reflux severity (grades IV and V), suggesting that the pop-off mechanism is unlikely to be the cause of contralateral reflux.

Adolescent↗

Cystic kidney diseases.

The goal of understanding the primary defects that lead to renal cystic diseases has proved to be an elusive one, despite 3 decades of physiologic and genetic investigation. Within the past 2 years the genes responsible for type 1 and type 2 autosomal dominant polycystic kidney disease have been identified. The process of defining the normal distribution and functions of the proteins encoded by these genes as well as the precise pathophysiology of cystogenesis is underway. For other major hereditary cystic kidney diseases, chromosomal localization or gene identification has also been achieved in recent years. Mouse and rat models of renal cystic disease continue to be a rich source of new data on the effect of genetic and environmental modifying factors on disease progression as well as serving as a preliminary testing ground for novel approaches to management such as gene therapy and early dietary modification. Ongoing clinical research continues to better define the renal and extra-renal manifestations of autosomal dominant polycystic and other renal cystic diseases. It is likely that a clearer understanding of the pathophysiology of these diseases will provide important insights into the processes that control tissue development and growth, and cellular differentiation.

Animals↗

Tear lactoferrin concentration during postoperative ocular inflammation in cataract surgery.

Tear lactoferrin concentration was measured by ELISA technique and followed in 30 patients undergoing cataract surgery. On the first day following surgery, there was a significant decrease in tear lactoferrin concentration followed by a gradual return to the initial values during the postoperative observation period of 7 days. There was an inverse linear relationship between tear lactoferrin concentration and the tear secretion rate measured by a modified Schirmer I test (1 min) suggesting a constant lactoferrin secretion by the tear glands. Since lactoferrin has known antibacterial and anti-inflammatory effects, the results may contribute to further understanding of the microbial vulnerability or resistance of the eye following surgical procedures.

Aged↗

Isolated angiitis of the CNS presenting as subarachnoid haemorrhage.

Isolated angiitis of the CNS (IACNS) commonly presents with recurrent ischaemic or haemorrhagic infarcts, but subarachnoid haemorrhage is rare. Three patients with IACNS and subarachnoid haemorrhage are reported. Florid granulomatous angiitis with Langhans and foreign body type giant cells was found at necropsy in a child with sudden death. In two other patients the diagnosis was made angiographically. In one patient multifocal infarcts on MRI became evident one week after subarachnoid haemorrhage despite initial treatment with prednisone. Subarachnoid haemorrhage may be the first presentation of IACNS. Characteristic radiographic findings may allow early diagnosis.

Anti-Inflammatory Agents↗

Modulation of propagation from an ectopic focus by electrical load and by extracellular potassium.

We previously developed a technique (R. Kumar, R. Wilders, R. W. Joyner, H. J. Jongsma, E. E. Verheijck, D. A. Golod, A. C. G. van Ginneken, and W. N. Goolsby. Circulation 94: 833-841, 1996) for study of a mathematical model cell with spontaneous activity, viz. a "real-time" simulation of a rabbit sinoatrial node cell (SAN model cell; R. Wilders, H. J. Jongsma, and A. C. van Ginneken. Biophys. J. 60: 1202-1216, 1991) simultaneously being electrically coupled via our "coupling clamp" [H. Sugiura and R. W. Joyner. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1591-H1604, 1992] circuit to a real, isolated ventricular myocyte. We now apply this technique to investigate effects of coupling conductance (Gc), cell size, and the modulation of membrane potential by elevated extracellular potassium concentration on the ability of an ectopic focus, represented by the SAN model cell, to successfully drive a ventricular cell. Values of Gc and the relative sizes of the two cells define three possible outcomes: 1) spontaneous pacing of the SAN model cell but not driving of the ventricular cell, 2) cessation of spontaneous pacing, or 3) pacing of the SAN model cell and driving of the ventricular cell. Below a critical size of the SAN model cell only the first two of these outcomes is possible. Above this critical size there is a range of Gc that allows successful operation of the system as an ectopic focus. Elevation of extracellular potassium concentration from 4 to 8 mM increases both the lower bound and upper bound of Gc for this range. Elevation of extracellular potassium concentration, as commonly observed in myocardial ischemia, may have effects on either inhibiting or releasing from inhibition an ectopic focus.

Animals↗

Inhibition of skin protein kinase C by psychotropic drugs.

Lipid-soluble psychotropics are often used to treat skin diseases with psychosomatic indications. Although these drugs are known to exert their effects through the central nervous system, relatively little is known about their mechanism of action in skin. In this communication, several lipid-soluble psychotropic drugs have been examined for their ability to inhibit protein kinase C (PKC)-catalyzed phosphorylation of exogenous substrates and endogenous skin proteins. Phosphorylation of three discrete skin protein substrates at 64, 42 and 28 kDa and a group crowded together at 15-18 kDa was prevented by the antidepressants/antipsychotics. Inhibition was more pronounced in a phospholipid (PL) dependent system, but both drug-PL and drug-PKC interactions seem to be important in the mechanism of action of these drugs. In addition to the tricyclic nucleus, the propanamine side chain or its N-methyl form may influence the interaction of these drugs with PKC and its substrate(s). Chlorpromazine, imipramine, fluoxetine, doxepin, amitriptyline and hydroxyzine used in the practice of dermatology may exert their therapeutic effects by modulating skin PKC activity.

Animals↗

Expression of guanylyl cyclase-A/atrial natriuretic peptide receptor blocks the activation of protein kinase C in vascular smooth muscle cells. Role of cGMP and cGMP-dependent protein kinase.

To understand the molecular mechanisms of cellular signaling of atrial natriuretic peptide (ANP), we have studied its effect on the enzymatic activity of endogenous and overexpressed protein kinase C (PKC) in rat thoracic aortic vascular smooth muscle (RTASM) cells. Angiotensin II (ANG II), endothelin-1 (ET-1), and 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated fourfold to fivefold PKC activity in PKC-alpha cDNA-transfected RTASM cells. However, pretreatment of these cells with ANP significantly inhibited the agonist-stimulated PKC activity in a dose-dependent manner. The inhibitory effect of ANP was more effective if cells were transfected with both PKC-alpha and guanylyl cyclase-A/atrial natriuretic peptide receptor (Npra) cDNAs. The agonist-stimulated PKC activity was also inhibited if RTASM cells were pretreated with cGMP analog 8-bromo-cGMP; however, the treatment of cells with a cAMP analog, dibutyryl-cAMP, did not show any discernible effect. The pretreatment of cells with Npra antagonist A-71915, significantly blocked the production of cGMP as well as the inhibitory effect of ANP on PKC activity. To further examine whether the antagonistic action of ANP and 8-bromo-cGMP on agonist-stimulated PKC activity were mediated through cGMP-dependent protein kinase (PKG), cells were treated with ANP or 8-bromo-cGMP and activators of PKC in the presence of KT-5823, a specific inhibitor of PKG. The treatment of cells with KT-5823 significantly attenuated the inhibitory effects of both ANP and 8-bromo-cGMP on agonist-stimulated PKC activity. The results from these studies provide strong evidence that ANP antagonizes the activation of PKC in RTASM cells, involving guanylyl cyclase-A receptor Npra and second messenger cGMP. Our data further support the notion that ANP acts as a negative mediator of signaling cross-talks between Npra and PKC in a cGMP-dependent manner, probably involving cGMP-dependent protein kinase in this process.

Angiotensin II↗

Serological characteristics of systemic lupus erythematosus from a hospital-based rheumatology clinic in Kuwait.

Thirty-one consecutive patients with SLE were screened for antinuclear antibody (ANA), anti-DNA antibodies, extractable nuclear antigen antibodies (anti-ENAs) including anti-Sm, anti-RNP, anti-SSA (anti-Ro), anti-SSB; (anti-La), anti-Scl-70, rheumatoid factor (RF), C-reactive protein (CRP), C3 and C4 levels, anti-cardiolipin antibodies (aCL), biologically false positive serological test for syphilis (BF-STS) using VDRL test and Coombs' test. The age of the patients ranged from 11 to 52 year with a median of 29 year; female to male ratio of 5:1. There were 21 Kuwaitis, four Egyptians, three from the Indian subcontinent, two Filipinos and one Syrian. Main clinical categories of SLE were: mild cutaneous SLE in 12 (38.7%), clinical antiphospholipid syndrome (APS) secondary to SLE in 8 (25.8%), haematological manifestations of SLE in 5 (16.1%), renal lupus in four (12.9%), neuropsychiatric in three (9.7%), others (6.4%). Clinical features overlapped in several patients. ANA was positive in 96.8% (mean value 891.61 units/ml), anti-DNA in 35.5% (mean value 56.4 units) that was lower than expected and could be due to selection bias as the patients were from a rheumatology clinic, anti-ENA in 42%, anti-Sm 13% that was lower than other non-Caucasian populations, anti-RNP 13%, anti-SS-A in 35.5%, anti-SS-B in 19.4%, Scl-70 in 13%, CRP in 71% (moderate 58%, very high 13%); C3 mean 1.52 mg/ml (3.2% low levels), C4 mean 0.35 mg/ml (32% low levels), anticardiolipin mean GPL 35.35 units (high 58%), mean MPL 10.61 units (high 26%), BF-STS in 6%, Coombs' test in 6%, RF positive in 36%. The only significant positive clinical associations observed were those of renal involvement with anti-DNA antibodies (P = 0.042), and clinical antiphospholipid antibody syndrome with aCL antibodies (P = < 0.05).

Adolescent↗