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Biomedical subjects

A Banerjee

Publications and source records attributed to A Banerjee.

At least 73 records · Page 4Linked to original sources

Evaluation of arterial stiffness in children with Williams syndrome: Does it play a role in evolving hypertension?

BACKGROUND: Pathologic studies and surgical observations of thickened aortic walls have suggested an increase in aortic stiffness in patients with Williams syndrome. However, in vivo objective evaluation of aortic and arterial stiffness in Williams syndrome are lacking. Moreover, systemic hypertension, although prevalent in Williams syndrome, does not have a well-defined mechanism in this syndrome. Therefore, the purpose of this study was to quantitate aortic stiffness and arterial compliance in an objective manner, as well as to determine their roles in development of hypertension, in children with Williams syndrome. METHODS: We studied 13 patients with Williams syndrome (aged 3-12 years) and 16 age-matched control subjects. Aortic stiffness was calculated from the beta index as follows: beta = (ln[P(s)/P(d)])/ ([D(s) - D(d)]/D(d)), where P(s) and P(d) are systolic and diastolic blood pressures and D(s) and D(d) are systolic and diastolic aortic dimensions, respectively. Arterial compliance (C) was calculated by the area method: C= (A(d) x CO x CL) / (A(t) x [P(es) - P(d)]), where A(t) is the total area and A(d) is the area under the diastolic portion of the arterial pulse tracing, CO is the cardiac output, CL is the cycle length, and P(es) is aortic end-systolic pressure. RESULTS: In patients with Williams syndrome, the beta index was 2-fold higher than in control patients (9.02 +/- 3.15 vs 4.43 +/- 0.96, P <.005). Moreover, there was a strong positive correlation between the beta index and the systolic blood pressure (r = 0.8 and P <.0001). Compliance was decreased by 42% (0.41 +/- 0.11 vs 0.71 +/- 0.10 mL/mm Hg, P <.05), suggesting decreased arterial compliance. CONCLUSIONS: Our study indicates that in vivo arterial stiffness is increased in patients with Williams syndrome. We speculate that increased arterial stiffness may be the predisposing cause of systemic hypertension in Williams syndrome.

Adolescent↗

Vascular cell adhesion molecule--1 expression is obligatory for endotoxin-induced myocardial neutrophil accumulation and contractile dysfunction.

BACKGROUND: Sepsis-induced cardiac dysfunction occurs commonly in critically ill patients and is associated with high mortality rates. Neutrophils play a central role in sepsis-induced lung and liver injury; however, the mechanism of sepsis-induced cardiac dysfunction remains unclear. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in neutrophil-mediated liver injury during endotoxemia and is also expressed in myocardium. The purposes of this study were to examine the temporal relationship of myocardial VCAM-1 expression with neutrophil accumulation during endotoxemia and to determine whether VCAM-1 mediates neutrophil accumulation and cardiac dysfunction during endotoxemia. METHODS: Mice were subjected to lipopolysaccharide (LPS; 0.5 mg/kg, intraperitoneally). Myocardial VCAM-1 expression and neutrophil accumulation were determined by immunofluorescence staining. Cardiac performance with or without VCAM-1 blocking antibody (5 mg/kg, intravenously) was determined by the Langendorff technique. RESULTS: LPS caused a time-dependent increase in both myocardial VCAM-1 expression and neutrophil accumulation. At 6 hours after LPS, the immunofluorescent intensity for VCAM-1 increased from 2.5 +/- 0.6 x 10(6) in saline solution controls to 19.9 +/- 3.5 x 10(6) (P <.05, analysis of variance), and neutrophil count increased from 2.4 +/- 1.7/mm(2) in saline solution controls to 13.0 +/- 2.5/mm(2) (P <.05). Left ventricular developed pressure was decreased maximally at 6 hours after LPS compared with saline solution controls (29.1 +/- 1.1 mm Hg vs 53.1 +/- 3.9 mm Hg; P <.05). Treatment with VCAM-1 monoclonal antibody abrogated both myocardial neutrophil accumulation and cardiac dysfunction during endotoxemia. CONCLUSIONS: LPS-induced myocardial dysfunction is associated with increased expression of VCAM-1 and with neutrophil accumulation. Blockade of VCAM-1 abrogates myocardial neutrophil accumulation and preserves cardiac function during endotoxemia, which supports a role for VCAM-1 as a therapeutic target for myocardial protection during sepsis.

Animals↗

Mitral valve endocarditis following balloon mitral valvotomy.

The case of a patient who developed fungal valve endocarditis due to Candida albicans following balloon mitral valvotomy is presented. The patient did not have any obvious predisposing factors which led to the development of fungal endocarditis.

Candida albicans↗

Recognition and stabilization of a unique CPRI--structural motif in cucurbitaceae family trypsin inhibitor peptides: molecular dynamics based homology modeling using the X-ray structure of MCTI-II.

The high resolution crystallographic structure of MCTI-II complexed with beta trypsin (PDB entry 1MCT) was used to model the corresponding structures of the six inhibitor peptides belonging to Cucurbitaceae family (MCTI-I, LA-1, LA-2, CMTI-I, CMTI-III, CMTI-IV). Two model inhibitors, LA-1 and LA-2 were refined by molecular dynamics to estimate the average solution structure. The difference accessible surface area (DASA) study of the inhibitors with and without trypsin revealed the Arginine and other residues of the inhibitors which bind to trypsin. The hydration dynamics study of LA1 and LA2 also confirm the suitability of water molecules at the active Arg site. Moreover, the presence of a unique 3D-structural motif comprises with the four CPRI residues from the amino terminal is thought to be conserved in all the six studied inhibitors, which seems essential for the directional fixation for proper complexation of the Arg (5) residue towards the trypsin S1-binding pocket. The role of the disulphide linkage in the geometrical stabilization of CPRI (Cysteine, Proline, Arginine, Isoleucine) motif has also been envisaged from the comparative higher intra molecular Cys (3) -Cys (20) disulphide dihedral energies.

Amino Acid Motifs↗

Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds.

Despite the fact that many modern drug therapies are based on the concept of enzyme inhibition, inhibition of several enzymes leads to pathological disorders. Clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) bind to the active site of the membrane protein, cyclooxygenase (COX) and inhibit the synthesis of prostaglandins, the mediators for causing inflammation. At the same time, inhibition of hepatic cysteine proteases by some NSAID metabolites like NAPQI is implicated in the pathogenesis of hepatotoxicity. As a part of our efforts to develop new effective NSAIDs, a comprehensive investigation starting from synthesis to the study of the final metabolism of acetanilide group of compound has been envisaged with appropriate feedback from kinetic studies to enhance our knowledge and technical competency to feed the know-how to the medicinal chemist to screen out and design new acetanilide derivatives of high potency and low toxicity. Structure-function relationship based on the interaction of acetanilide with its cognate enzyme, cyclooxygenase has been studied critically with adequate comparison with several other available crystal structures of COX-NSAID complexes. Furthermore, to make the receptor based drug design strategy a novel and comprehensive one, both the mechanism of metabolism of acetanilide and structural basis of inhibition of cysteine proteases by the reactive metabolite (NAPQI) formed by cytochrome P450 oxidation of acetanilide have been incorporated in the study. It is hoped that this synergistic approach and the results obtained from such consorted structural investigation at atomic level may guide to dictate synthetic modification with judicious balance between cyclooxygenase inhibition and hepatic cysteine protease inhibition to enhance the potential of such molecular medicine to relieve inflammation on one hand and low hepatic toxicity on the other.

Acetanilides↗

Evidence for an essential arginine in the flavoprotein nitroalkane oxidase.

The flavoprotein nitroalkane oxidase from the fungus Fusarium oxysporum catalyzes the oxidative denitrification of primary or secondary nitroalkanes to yield the respective aldehydes or ketones, hydrogen peroxide and nitrite. The enzyme is inactivated in a time-dependent fashion upon treatment with the arginine-directed reagents phenylglyoxal, 2,3-butanedione, and cyclohexanedione. The inactivation shows first order kinetics with all reagents. Valerate, a competitive inhibitor of the enzyme, fully protects the enzyme from inactivation, indicating that modification is active site directed. The most rapid inactivation is seen with phenylglyoxal, with a k(inact) of 14.3 +/- 1.1 M(-1) min(-1) in phosphate buffer at pH 7.3 and 30 degrees C. The lack of increase in the enzymatic activity of the phenylglyoxal-inactivated enzyme after removing the unreacted reagent by gel filtration is consistent with inactivation being due to covalent modification of the enzyme. A possible role for an active site arginine in substrate binding is discussed.

Arginine↗

Wegener's granulomatosis presenting as acute suppurative interstitial nephritis.

A 78 year old man presented with acute renal failure following a prolonged respiratory illness. A renal biopsy demonstrated severe suppurative interstitial nephritis with normal glomeruli. After nine weeks of antibiotics he remained anuric and a second biopsy demonstrated pauci-immune, necrotising glomerulonephritis. His subsequent clinical course was consistent with a diagnosis of Wegener's granulomatosis and antineutrophil cytoplasmic antibodies (ANCA) were detected. This is the first reported case of Wegener's granulomatosis presenting with an isolated tubulointerstitial lesion.

Acute Disease↗

Role of SNAP-23 in trafficking of H+-ATPase in cultured inner medullary collecting duct cells.

The trafficking of H+-ATPase vesicles to the apical membrane of inner medullary collecting duct (IMCD) cells utilizes a mechanism similar to that described in neurosecretory cells involving soluble N-ethylmaleimide-sensitive factor attachment protein target receptor (SNARE) proteins. Regulated exocytosis of these vesicles is associated with the formation of SNARE complexes. Clostridial neurotoxins that specifically cleave the target (t-) SNARE, syntaxin-1, or the vesicle SNARE, vesicle-associated membrane protein-2, reduce SNARE complex formation, H+-ATPase translocation to the apical membrane, and inhibit H+ secretion. The purpose of these experiments was to characterize the physiological role of a second t-SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)-23, a homologue of the neuronal SNAP-25, in regulated exocytosis of H+-ATPase vesicles. Our experiments document that 25-50 nM botulinum toxin (Bot) A or E cleaves rat SNAP-23 and thereby reduces immunodetectable and (35)S-labeled SNAP-23 by >60% within 60 min. Addition of 25 nM BotE to IMCD homogenates reduces the amount of the 20 S-like SNARE complex that can be immunoprecipitated from the homogenate. Treatment of intact IMCD monolayers with BotE reduces the amount of H+-ATPase translocated to the apical membrane by 52 +/- 2% of control and reduces the rate of H+ secretion by 77 +/- 3% after acute cell acidification. We conclude that SNAP-23 is a substrate for botulinum toxin proteolysis and has a critical role in the regulation of H+-ATPase exocytosis and H+ secretion in these renal epithelial cells.

Animals↗

On the phase-space dynamics of systems of spiking neurons. I: model and experiments.

We investigate the phase-space dynamics of a general model of local systems of biological neurons in order to deduce the salient dynamical characteristics of such systems. In this article, we present a detailed exposition of an abstract dynamical system that models systems of biological neurons. The abstract system is based on a limited set of realistic assumptions and thus accommodates a wide range of neuronal models. Simulation results are presented for several instantiations of the abstract system, each modeling a typical neocortical column to a different degree of accuracy. The results demonstrate that the dynamics of the systems are generally consistent with that observed in neurophysiological experiments. They reveal that the qualitative behavior of the class of systems can be classified into three distinct categories: quiescence, intense periodic activity resembling a state of seizure, and sustained chaos over the range of intrinsic activity typically associated with normal operational conditions in the neocortex. We discuss basic ramifications of this result with regard to the computational nature of neocortical neuronal systems.

Action Potentials↗

On the phase-space dynamics of systems of spiking neurons. II: formal analysis.

We begin with a brief review of the abstract dynamical system that models systems of biological neurons, introduced in the original article. We then analyze the dynamics of the system. Formal analysis of local properties of flows reveals contraction, expansion, and folding in different sections of the phase-space. The criterion for the system, set up to model a typical neocortical column, to be sensitive to initial conditions is identified. Based on physiological parameters, we then deduce that periodic orbits in the region of the phase-space corresponding to normal operational conditions in the neocortex are almost surely (with probability 1) unstable, those in the region corresponding to seizure-like conditions are almost surely stable, and trajectories in the region corresponding to normal operational conditions are almost surely sensitive to initial conditions. Next, we present a procedure that isolates all basic sets, complex sets, and attractors incrementally. Based on the two sets of results, we conclude that chaotic attractors that are potentially anisotropic play a central role in the dynamics of such systems. Finally, we examine the impact of this result on the computational nature of neocortical neuronal systems.

Action Potentials↗

Wegener's granulomatosis: diagnostic dilemma.

Wegener's granulomatosis is a systemic disease characterized by a granulomatous lesion that can affect any organ throughout the body. This case-report illustrates the problem posed by a patient presenting with bilateral serous otitis media with marked sensorineural hearing loss, facial nerve paralysis and an atypical serological picture. The importance of early diagnosis and the protocol for the management of a patient with an uncertain diagnosis is discussed. Due to atypical presentations, only a high index of suspicion will ensure an early diagnosis.

Acute Disease↗

Alveolar rhabdomyosarcoma of the parotid gland.

Alveolar rhabdomyosarcoma of the parotid gland is a rare condition. The treatment should involve an aggressive multi-modality approach incorporating surgical removal of the tumour, radiotherapy, and multi-agent chemotherapy. The presentation of this condition along with the most appropriate line of treatment is discussed.

Adult↗

Application of seminal germ cell morphology and semen biochemistry in the diagnosis and management of azoospermic subjects.

AIM: To evaluate whether the study of seminal germ cell morphology (SGCM) and semen biochemistry could be fruitfully utilized for the diagnosis and management of azoospermic subjects. METHODS: In the semen, mature and immature germ cells are contributed by the testes, 70% of glycerylphosphoryl choline (GPC) by the epididymis, fructose mostly or solely by the seminal vesicles and acid phosphatase [corrected] (ACP) by the prostate. In 16 normal volunteers, 12 vasectomized subjects and 186 azoospermic subjects, these parameters have been studied and the data have been analyzed. RESULTS: Both mature and immature germ cells are absent in the semen of vasectomized subjects as well as in obstructive azoospermia; GPC level is also significantly decreased in both these groups. In cases with non-obstructive azoospermia immature germ cells are present and seminal GPC, ACP and fructose levels are normal. The diagnosis of obstructive and non-obstructive azoospermia based on these parameters correlated well with "correct" testicular biopsy findings. In some cases of azoospermia due to hypospermatogenesis or spermatogenic developmental arrest, the SGCM studies were very helpful in objectively monitoring the response of the germinal tissue to specific treatments. CONCLUSION: SGCM and semen biochemical parameters are very valuable non-invasive markers for differentiating obstructive from non-obstructive azoospermia. The SGCM findings serve as a dependable non-invasive testicular marker with high predictive value.

Adult↗

A unified treatment regimen for new cases of tuberculosis in resource-poor countries: a study in a rural district in Malawi.

An oral ambulatory unified treatment regimen was introduced in Ntcheu District, Malawi, between April 1996 and June 1997 for all new patients (600) with tuberculosis (TB). There was no change in the case finding pattern compared with the previous 5 years; 65% of new smear-positive pulmonary tuberculosis (PTB) patients completed treatment, not significantly different compared with the previous 3 years. Treatment completion was significantly lower in patients with smear-negative PTB and extra-pulmonary tuberculosis, due mainly to high mortality rates (40% and 41% respectively). In a rural district with high human immunodeficiency virus sero-prevalence rates in TB patients, case finding and end of treatment outcome of the oral unified regimen were comparable to those of previous regimens.

Antitubercular Agents↗

Dentine caries: take it or leave it?

In modern dentistry the primary aim when excavating carious dentine is to eradicate only the highly infected, irreversibly demineralised and denatured biomass in order to allow effective restoration of the cavity, restoration of the surface anatomy of the tooth and to prevent disease progression. However, the boundary between this superficial zone of dentine requiring excavation and the deeper, affected but repairable tissue is not always obvious either in the clinic or in the research laboratory. The inherent subjectivity in detecting this excavation boundary can result in clinically significant differences in the quality and quantity of dentine removed by different operators and makes the in vitro comparison of newer excavation techniques more difficult. This article discusses the rationale behind carious dentine excavation and the criteria available to the dentist, both clinical and laboratory, to help identify the dentine requiring removal.

Color↗

Can guardians supervise TB treatment as well as health workers? A study on adherence during the intensive phase.

SETTING: In sub-Saharan Africa, tuberculosis (TB) has increased over the last two decades due to the human immunodeficiency virus pandemic. In Malawi, 20630 new TB patients were notified to the National Tuberculosis Programme in 1996, a fourfold increase since 1986. Due to this increase in cases and lack of resources (both human and monetary) it is becoming more difficult to ensure directly observed treatment (DOT) in the TB wards. METHODS: In Ntcheu district, Malawi, a new TB regimen was introduced from April 1996 in which patients received supervised treatment by either a health worker or a guardian (i.e., family member). Adherence to the different treatment options was measured by form checks, tablet counts, and tests for detecting isoniazid in the urine. Adherence was measured at 2, 4 and 8 weeks after onset of TB treatment. RESULTS: Overall adherence rate was 95-96%. Inpatients showed the highest adherence rates. Patients on guardian-based DOT (GB-DOT) (n = 35) showed 94% adherence, while patients on health centre based DOT (n = 40) showed more non-adherent behaviour: 11% according to monitoring forms, 14% according to tablet counts and 16% according to urine tests. DISCUSSION: The results suggest that decentralised care is a feasible option for anti-tuberculosis treatment and that guardians can supervise TB treatment just as well as health workers during the intensive phase of TB treatment.

Adult↗