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Biomedical subjects

D Jain

Publications and source records attributed to D Jain.

At least 19 recordsLinked to original sources
PubMed2006

Clear cell meningioma, an uncommon variant of meningioma: a clinicopathologic study of nine cases.

AIMS: Clear cell meningioma (CCM) is an uncommon variant of meningioma, which affect younger patients, occur more often in spinal or cerebello pontine locations and shows a higher recurrence rate. Only few case reports have been described in the literature. The study has been undertaken to document the clinicopathological features of nine cases of CCM, operated at All India Institute of Medical Sciences during 1998 to December 2005. METHODS: Clinical information was retrieved from the records of our Neurosurgery Department. The cases were stained with H&E, periodic Acid Schiff (PAS) with and without diastase. Immunohistochemistry for pancytokeratin, epithelial membrane antigen, vimentin, glial fibrillary acidic protein, and MIB-1 was done in all cases. RESULTS: During a period of 8 years, nine cases of CCM were diagnosed. Age ranged from 10 to 65 years (median age 26.0 years) with female predominance. Most common location was posterior fossa (CP angle). Clinically most of the patients presented with history of headache and features of cranial nerve palsies. The duration of symptoms varied from 3 to 60 months (mean 16.7 and median of 4 months). Radiologically lesions showed homogenous enhancement and were isointense to brain parenchyma. Histopathologic examination revealed tumor cells to be arranged in sheets with clear cytoplasm and monomorphic nuclei. MIB-1 labeling index (LI) ranged from 2 to 12% with a mean of 9%. Follow up varied from 3 to 84 months (median 36 months) and recurrence was noted in two patients after 2 and 3 years of surgery, respectively, despite their low MIB-1 labeling indices. CONCLUSIONS: CCM is a rare variant of meningioma with poor outcome. Less than 50 cases have been described in the literature. Low rate of recurrence and recurrence despite their low MIB-1 LI are some of the features, which needs to be documented. Hence, larger number of cases with adequate follow-up data need to be studied further to establish the clinical significance of this variant.

Adolescent↗
PubMed2004

Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study.

OBJECTIVE: To study the efficacy of alendronate, in the treatment of avascular necrosis (AVN) of the hip. METHODS: Sixty patients with AVN of the hip (100 hips with AVN) were studied. The follow-up period ranged from 3 months to 5 yr. The most common cause of AVN was steroids. Parameters studied were walking time, standing time, pain and disability on a visual analogue scale (VAS), range of motion of the hip, X-ray and MRI of the hip. All patients were treated with alendronate 10 mg/day (or 70 mg/week) along with 500-1000 mg of daily calcium and vitamin D supplements, and were advised to avoid weight-bearing. NSAIDs and analgesics were permitted as needed and were recorded. RESULTS: Forty-one patients (71 AVN hips) with AVN have been followed up for a minimum of 1 yr, 24 patients (42 AVN hips) for 2 yr and 21 patients (37 AVN hips) for more than 2 yr (average 37 month). Fourteen patients have been followed up for less than 1 yr (3-9 months). Significant reduction in pain and disability scores (P < 0.001) and significant increase in standing and walking time (P < 0.001) were observed. All hip movements improved at 1 yr (P value 0.000-0.009) with an insignificant decline after that (P > 0.001). Radiologically, the hips either stabilized in the same grade or progressed by one grade. MRI showed a decrease in marrow oedema in most cases at the 1-yr follow-up. Six patients (10 hips) required surgery and there were two (three hips) dropouts. The drug was well tolerated and there was a reduction in NSAID requirement. CONCLUSION: Alendronate reduces pain, improves function and retards AVN progression. Early surgical intervention can be avoided in most patients.

Adolescent↗
PubMed2004

Violence against women in India: evidence from rural Maharashtra, India.

INTRODUCTION: In recent years violence against women has emerged as an important social problem in India. It has attracted the attention of a wide spectrum of agencies, from healthcare providers to law enforcement authorities. This study attempted to determine the characteristics and the magnitude of physical and psychological violence against women in rural Maharashtra, central India. METHODS: The study initially undertook focus group activities. This was followed by the formulation of the survey instrument in English, which focused on partner violence and child disciplinary practices. After pre-testing the instrument in 25 households, the actual study was conducted by trained interviewers in five randomly selected villages of rural Maharashtra. The study included 500 households (sample size = 500 women, eligible if they had at least one child less than 18 years of age). RESULTS: The results revealed that of the women interviewed, almost one-third (30.4%) had no formal education and the women's husbands were better educated. More than half the women lived in one-room dwellings and were at or above the clinical cut-off point for depression on the Center for Epidemiologic Studies Depression Scale (CES-D). 38% of the women were verbally insulted by their husband with a median of 11 times in past 6 months. Almost half the women said they had been slapped, hit, kicked or beaten by their husbands at some time. 24% of the women reported having been kicked by their husbands at some point during their married life, and 44% were reportedly kicked during pregnancy. 12% were specifically threatened by their husbands with having kerosene oil poured on them to set them on fire. 30% of the physically assaulted victims required medical care. CONCLUSIONS: Considering the prevalence of domestic violence, health-care providers should screen for domestic violence in routine practice. In addition, protocols should be developed for referral of abused women to appropriate community resources. In the present Indian rural setting, solutions to domestic violence must be found within the social structure of the family and the community.

Journal Article↗
PubMed2003

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Aged↗
PubMed2003

Impact of myocardial perfusion imaging on clinical management and the utilization of hospital resources in suspected acute coronary syndromes.

Recent advances in the treatment of acute coronary syndromes has raised awareness in the community that prompt presentation for chest pain may be life saving. Each year in the United States, more than 6 million people present to the hospital with an acute chest pain, making this the most common presenting chief complaint second only to abdominal pain. Most patients presenting with chest discomfort have a non-ischaemic electrocardiogram on presentation. However, these patients are routinely admitted to hospital due to diagnostic uncertainty for occult myocardial infarction or ischaemia. As an approach to this dilemma, many hospitals have created protocols as a means of facilitating the identification of infarction and ischaemia and the safe and effective triage of patients with a chief complaint of chest pain. Myocardial perfusion imaging at rest has been shown to be highly sensitive for the detection of acute myocardial infarction, and can be supplemented with provocative testing after infarction has been excluded. Diagnostic strategies that utilize myocardial perfusion imaging for the evaluation of acute chest pain have successfully improved the triage of these patients by avoiding inadvertent discharge of patients with myocardial infarctions, and reducing unnecessary hospital admissions and overall cost and expenditure.

Acute Disease↗
PubMed2003

Prevalence and characteristics of migraine among adolescents: a questionnaire survey.

A screening questionnaire was distributed to 1000 boys and 1000 girls, studying in classes VI to X (11 to 15 years) in two public schools of Jaipur. Questionnaire A consisted of a single question to parents. "Does your child suffer from recurrent headache?" To those who responded in the affirmative, a detailed questionnaire (B) was distributed Questionnaire B consisted of twenty questions pertaining to characteristics and associations of headache. From questionnaire B a diagnosis of common migraine was made according to IHS criteria (1988). The prevalence of recurrent headache was found to be 18% in boys and 21% in girls, while the prevalence of migraine was 9% in boys and 14% in girls. Among the other causes of recurrent headache tension type headache was seen in 3.6%, eye problems in 0.389% sinusitis in 0.22%, and undetermined etiology in 2.14% children. The clinical characteristics of migraine are described.

Adolescent↗
PubMed2002

Efficiency comparison between 99m Tc-tetrofosmin and 99m Tc-sestamibi myocardial perfusion studies.

The purpose of this investigation was to compare the efficiency of two different imaging protocols using two different clinically available 99mTc labelled myocardial perfusion tracers. One thousand one hundred and thirty-four imaging studies were performed prospectively, using either 99mTc-tetrofosmin or 99mTc-sestamibi, alternating the use of each tracer for a total period of 8 months. 99mTc-tetrofosmin rest studies were performed with injections of 259MBq-370MBq and imaging 30 min later. Exercise studies were performed with injections of 777MBq-1.11GBq and imaging 20 min later. 99mTc-sestamibi studies used doses similar to those in the 99mTc-tetrofosmin studies. Imaging followed a standard procedure, at 60 min after rest injection, and 30 min after exercise. For patients undergoing pharmacological stress testing99mTc-sestamibi was imaged 45 min after injection and 99mTc-tetrofosmin was imaged 30 min after injection. Variables analysed were (1) injection-to-imaging time for the procedure, and (2) the number of repeated scans because of extra cardiac activity. The completion time for the rest study was significantly shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (47.7+/-21.7 min vs 74.3+/-25.8 min P<0.0001). Likewise, the total study time was shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (90+/-32.7 min vs 124+/-37 min, P<0.0001). More importantly, the number of repeated scans was higher with 99mTc-sestamibi compared to 99mTc-tetrofosmin, 21.4% vs 10%, P=0.001 for rest studies and 16.4% vs 7.9% P=0.001 [corrected] for rest and stress. It was concluded that, using a same day rest/stress protocol, 99mTc-tetrofosmin provided higher patient throughput with fewer repeat scans. These factors may be considered for efficiency improvement in nuclear cardiology laboratories using 99mTc perfusion tracers.

Adenosine↗
PubMed2001

Enhanced binding of a rationally designed peptide ligand of concanavalin a arises from improved geometrical complementarity.

The structural basis of affinity enhancement was addressed by analyzing the interactions between concanavalin A and the carbohydrate-mimicking peptide ligands. Based on the crystal structures of concanavalin A in complex with these peptides [Jain, D., Kaur, K. J., Sundaravadivel, B., and Salunke, D. M. (2000) J. Biol. Chem. 275, 16098-16102; Jain, D., Kaur, K. J., and Salunke, D. M. (2001) Biophys. J. 80, 2912-2921], a high-affinity analogue was designed. This analogue (acetyl-MYWYPY-amide) binds to the lectin with 32-fold enhanced affinity compared to the corresponding precursor peptides. The crystal structure of concanavalin A bound to the designed peptide has been determined. A peptide molecule binds to each of the crystallographically independent monomers of the tetrameric lectin. The four bound peptide molecules exhibit two major conformations both of which are extended. Unlike in the case of other concanavalin A binding peptides, the structural variations within different conformers of this analogue are marginal. It is apparent that the deletion of the structurally variable region of the larger peptides has led to an improved complementarity and increased buried surface area in the case of the designed peptide. The crystal structure also showed the formation of two backbone hydrogen bonds between the ligand and the ligate which were not present in the complexes of the precursor peptides. The observed structural features adequately explain the enhanced binding of the designed analogue.

Concanavalin A↗
PubMed2001

Structure of the induced antibacterial protein from tasar silkworm, Antheraea mylitta. Implications to molecular evolution.

The crystal structure of an antibacterial protein of immune origin (TSWAB), purified from tasar silkworm (Antheraea mylitta) larvae after induction by Escherichia coli infection, has been determined. This is the first insect lysozyme structure and represents induced lysozymes of innate immunity. The core structure of TSWAB is similar to c-type lysozymes and alpha-lactalbumins. However, TSWAB shows significant differences with respect to the other two proteins in the exposed loop regions. The catalytic residues in TSWAB are conserved with respect to the chicken lysozyme, indicating a common mechanism of action. However, differences in the noncatalytic residues in the substrate binding groove imply subtle differences in the specificity and the level of activity. Thus, conformational differences between TSWAB and chicken lysozyme exist, whereas functional mechanisms appear to be similar. On the other hand, alpha-lactalbumins and c-type lysozymes exhibit drastically different functions with conserved molecular conformation. It is evident that a common molecular scaffold is exploited in the three enzymes for apparently different physiological roles. It can be inferred on the basis of the structure-function comparison of these three proteins having common phylogenetic origin that the conformational changes in a protein are minimal during rapid evolution as compared with those in the normal course of evolution.

Amino Acid Sequence↗
PubMed2001

Functional equality in the absence of structural similarity: an added dimension to molecular mimicry.

The crystal structure of meso-tetrasulfonatophenylporphyrin complexed with concanavalin A (ConA) was determined at 1.9 A resolution. Comparison of this structure with that of ConA bound to methyl alpha-d-mannopyranoside provided direct structural evidence of molecular mimicry in the context of ligand receptor binding. The sulfonatophenyl group of meso-tetrasulfonatophenylporphyrin occupies the same binding site on ConA as that of methyl alpha-d-mannopyranoside, a natural ligand. A pair of stacked porphyrin molecules stabilizes the crystal structure by end-to-end cross-linking with ConA resulting in a network similar to that observed upon agglutination of cells by lectins. The porphyrin binds to ConA predominantly through hydrogen bonds and water-mediated interactions. The sandwiched water molecules in the complex play a cementing role, facilitating favorable binding of porphyrin. Seven of the eight hydrogen bonds observed between methyl alpha-d-mannopyranoside and ConA are mimicked by the sulfonatophenyl group of porphyrin after incorporating two water molecules. Thus, the similarity in chemical interactions was manifested in terms of functional mimicry despite the obvious structural dissimilarity between the sugar and the porphyrin.

Binding Sites↗
PubMed2001

Use of paclitaxel in patients with pre-existing cardiomyopathy: a review of our experience.

Cardiac toxicity is frequently the indication for discontinuation of an anthracycline in patients with tumors which remain anthracycline-sensitive. During the 1990s, the most frequently used second-line agents at the Yale Cancer Center (YCC) were the taxanes. The goal of this retrospective analysis was to determine the effect of paclitaxel on cardiac function in patients with cardiomyopathy. YCC outpatient clinic pharmacy order forms were used to identify all patients who had received paclitaxel between December 1995 and November 1997. The clinic records of those patients with a left ventricular ejection fraction (LVEF) of < or = 50% were reviewed to determine the temporal relation between the decreased LVEF and paclitaxel therapy. In addition, clinic records were examined for evidence of prior doxorubicin therapy and history of prior cardiac disease. Between December 1995 and November 1997, 225 patients were treated with paclitaxel in the YCC outpatient clinic. Nine patients had LVEF < or = 50% (mean 37%) prior to initiation of paclitaxel therapy. Six of these patients had equilibrium radionuclide angiocardiographic (ERNA) scans following completion of paclitaxel. In these 6 patients, the mean change in LVEF was +6% (range -3% to +29%). Four patients had improved LVEF following paclitaxel (mean 11%, range 2% to 29%), while 2 patients experienced a decrease in LVEF following paclitaxel treatment (mean 2.5%). The 3 patients who did not have ERNA scans following paclitaxel therapy had no clinical evidence of congestive heart failure. Our experience confirms the results of prior studies that paclitaxel can be safely administered in patients with underlying cardiac dysfunction.

Aged↗
PubMed2001

Immunological implications of structural mimicry between a dodecapeptide and a carbohydrate moiety.

The immunogenicity and antibody cross-reactivity of two chemically different but structurally equivalent molecular mimics were analyzed by presenting them to the immune system in different modes. The observed differences in IgM and IgG responses in terms of cross-reactivity with the mimicking antigen could reflect the differential proliferative abilities of the corresponding B-cells. Modification of the T-cell help, either by using a promiscuous T-cell epitope or by prepriming, led to the shift in the antibody response towards the mimicking epitope. Also, the anti-sugar antibodies could be boosted using a carbohydrate mimicking peptide on cross-immunization. Thus, the carbohydrate-peptide mimicry appears to be a topological quasi-equivalence reflected differently in terms of antibody response during maturation.

Amino Acid Sequence↗
PubMed2001

A unique pitfall in percutaneous coronary angioplasty of in-stent restenosis: guidewire passage out of the stent.

Three cases of in-stent restenosis are narrated, wherein, during balloon angioplasty of the lesion, the guidewire inadvertently exited out of the stent. The forward balloon progress was halted in this region. In the first case, the situation could only be realized when dilatation of a forcefully pushed small balloon avulsed the well-embedded stent. The mishap was averted in the subsequent two cases by reintroduction of a new guidewire. Some suggestions to avoid this eventuality are offered. Though the cases pertain to in-stent restenosis, the observations may be applicable to the procedures in general that entail passage of a guidewire through a stented area.

Aged↗
PubMed2001

Plasticity in protein-peptide recognition: crystal structures of two different peptides bound to concanavalin A.

The structures of concanavalin A (ConA) in complex with two carbohydrate-mimicking peptides, 10-mer (MYWYPYASGS) and 15-mer (RVWYPYGSYLTASGS) have been determined at 2.75 A resolution. In both crystal structures four independent peptide molecules bind to each of the crystallographically independent subunits of ConA tetramer. The peptides exhibit small but significant variability in conformations and interactions while binding to ConA. The crystal structure of another similar peptide, 12-mer (DVFYPYPYASGS), in complex with ConA has been determined (Jain, D., K. J. Kaur, B. Sundaravadivel, and D. M. Salunke. 2000. Structural and functional consequences of peptide-carbohydrate mimicry. J. Biol. Chem. 275:16098-16102). Comparison of the three complexes shows that the peptides bind to ConA at a common binding site, using different contacting residues and interactions depending on their sequence and the local environment at the binding site. The binding is also optimized by corresponding plasticity of the peptide binding site on ConA. The diversity in conformation and interactions observed here are in agreement with the structural leeway concerning plasticity of specific molecular recognition in biological processes. The adaptability of peptide-ConA interactions may also be correlated with the carbohydrate-mimicking property of these peptides.

Concanavalin A↗
PubMed2001

Adenosine inhibits norepinephrine release in the postischemic rat heart: the mechanism of neuronal stunning.

OBJECTIVE: Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we assessed the role of presynaptic adenosine-receptors and alpha2-adrenoceptors in neuronal stunning. METHODS AND RESULTS: Exocytotic NE release was induced by two electrical field stimulations (S(1) and S(2)) in isolated perfused rat hearts. S(1) was performed under baseline conditions and S(2) either during or following intervention. Results are expressed as mean S(2)/S(1) ratios+/-S.E.M. Stepwise increase of global ischemic periods (10, 20, and 30 min) induced a progressive suppression of NE release in the postischemic hearts, which was reversible during reperfusion. Both the degree and duration of NE suppression was dependent on the extent of the preceding ischemic period. Following 10-min ischemia complete recovery of NE release was achieved after 5-min reperfusion (1.07+/-0.12), whereas 5-min reperfusion did not restore NE release after 30 min (0.36+/-0.07) of ischemia. The adenosine-receptor antagonists 8-phenyltheophylline (8-PT; non-selective) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; adenosine A1-receptor subtype selective) significantly increased NE release after 30-min ischemia and 5-min reperfusion (0.78+/-0.06 and 0.64+/-0.07), while in the same experimental protocol blockade of alpha2-adrenoceptors by yohimbine failed to restore the postischemic release (0.24+/-0.06). In non-ischemic hearts the adenosine analogue R(-)N(6)-(2-phenylisopropyl)adenosine (R-PIA) resulted in a marked suppression of NE release (0.61+/-0.07). The inhibitory effect of R-PIA and 2-chloro-N(6)-cyclopentyladenosine (CCPA; adenosine A1-receptor subtype selective agonist) persisted 5 min after cessation of R-PIA (0.62+/-0.05) and CCPA (0.58+/-0.04). Activation of alpha2-adrenoceptors by 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) also caused a reduction of NE release (0.50+/-0.02), but the release increased to control levels 5 min after cessation of UK 14,304 (0.90+/-0.06). CONCLUSIONS: The results establish the phenomenon of neuronal stunning in terms of a postischemic suppression of exocytotic NE release and provide evidence that neuronal stunning is mediated by endogenous adenosine through activation of presynaptic adenosine A1-receptors.

Adenosine↗
PubMed2001

Antiplatelet therapy in acute coronary syndromes without persistent ST-segment elevation.

The treatment of ACS without persistent ST-segment elevation is evolving. Antiplatelet and antithrombin therapy forms the mainstay of medical management. The antiplatelet agents studied can be pharmacologically classified as GP lIb/IIIa receptor antagonists, ADP receptor antagonists, thromboxane inhibitors, and cyclo-oxygenase inhibitors. While aspirin, a cyclo-oxygenase inhibitor, is well entrenched in the treatment (and thus will not be reviewed here), other drugs have been subjects of intense study and large-scale clinical trials in the last decade. In this article we will explore the rationale of using antiplatelet agents, describe the platelet biology and mechanism of action of these drugs, narrate the major phase III trials, and attempt to draw conclusions from the clinical experience. Important trials which have been presented at principal international scientific meetings and which have not yet been published are also cited.

Acute Disease↗