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Biomedical subjects

M K Jain

Publications and source records attributed to M K Jain.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelium and atherosclerosis.

Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including the appropriate regulation of blood flow, a basal anti-inflammatory state, promotion of fibrinolysis while opposing blood coagulation, and control of the balance of cellular proliferation and death. Alterations in these endothelial homeostatic mechanisms contribute critically to atherogenesis, the progression of this disease, and ist complications. Recent advances have highlighted novel molecular mechanisms that regulate the atheroprotective functions of normal endothelial cells that go awry during atherogenesis. Therapeutic strategies that alter the course of atherosclerosis may act by combating endothelial dysfunction.

Animals↗
PubMed2006

Myocarditis and multiple cerebral and cerebellar infarction following scorpion sting.

An unusual case of scorpion sting followed by multiple cerebral and cerebellar watershed infarctions is being reported. Myocarditis, hypotension and hypoperfusion infarction is being considered as the possible explanation for this pathology. Hypoperfusion leading to parieto-occipital infarction has been reported earlier, however cerebellar infarction in this context is extremely rare.

Adult↗
PubMed2005

Role of transforming growth factor-beta1/Smads in regulating vascular inflammation and atherogenesis.

Accumulating evidence supports the role of inflammation in the development of a variety of chronic vascular diseases such as atherosclerosis, transplantation arteriosclerosis, and restenosis after vascular mechanical injury. Thus, identification of mechanisms to control inflammation may provide novel therapeutic targets to limit such disease states. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic growth factor with potent immunomodulating effects on cells important to atherosclerotic lesion formation including endothelial cells, vascular smooth muscle cells, macrophages, and T cells. The mechanisms responsible for the protective, anti-inflammatory effects of TGF-beta1 have recently become elucidated. This review focuses on the emerging role of the downstream TGF-beta1 signaling mediators, termed Smads, as regulators of vascular inflammation. These findings are beginning to establish a mechanistic scaffold with which to understand the cell-type specific function of Smads in the development of chronic inflammatory vascular disease states.

Animals↗
PubMed2003

Gabapentin in the management of pentazocine dependence: a potent analgesic--anticraving agent.

OBJECTIVES: To evaluate the role of Gabapentin in the management of Pentazocine dependence for suppressing muscle aching and craving during its withdrawal. MATERIAL AND METHODS: Patients of Pentazocine dependence were divided in two groups GpA and GpB (n = 10 in each) and were administered Clonidine (P.O.) in first seven days (acute detoxification phase) and later Naltrexone (P.O.) from seventh day onwards (stabilisation-maintenance phase). Gabapentin (1200 mg/day) was additionally added in group B. Muscle pain and craving were rated on 100 mm visual-analogue scale. Psychological dependence was assessed on four step categorical scale. RESULTS: Group B (Gabapentin group) scored significantly lower (p < 0.001) than group A on both the parameters. Psychological dependence was significantly low (p < 0.01) in Gabapentin group. CONCLUSION: Gabapentin is an important adjuvant to the management of opiate dependence both in acute detoxification as well as stabilisation phase.

Acetates↗
PubMed2002

Electrically enhanced ethanol fermentation by Clostridium thermocellum and Saccharomyces cerevisiae.

Ethanol production by Clostridium thermocellum ATCC 35609 and Saccharomyces cerevisiae ATCC 26603 was improved in an electrochemical bioreactor system. It was increased by 61% with Cl. thermocellum and 12% with S. cerevisiae in the presence of -1.5 V of electric potential. These increases were attributed to high production rates due to regeneration and availability of increased reduced equivalents in the presence of electric potential. The electric current caused considerable shift in the metabolite concentrations on a molar basis in Cl. thermocellum fermentation but less in S. cerevisiae fermentation. Increasing electric potential in Cl. thermocellum fermentation resulted in less acetate and more lactate production. Acetate production was also reduced with increased electric potential in S. cerevisiae fermentation. The high electric potential of -5 V adversely affected the Cl. thermocellum fermentation, but not the S. cerevisiae fermentation even at a high electric potential of -10 V.

Bioreactors↗
PubMed2001

The basis for k(cat) impairment in prophospholipase A(2) from the anion-assisted dimer structure.

Kinetic results in this paper show that, contrary to earlier reports, pig pancreatic prophospholipase A(2) (proPLA2) does not hydrolyze monodisperse short chain phosphatidylcholine below the critical micelle concentration. ProPLA2 is active on an anionic interface, but at a rate that is decreased by more than 100-fold compared to that of PLA2, the active form. Solution studies show that both proPLA2 and PLA2 bind to an anionic interface and also bind a tetrahedral intermediate mimic at the active site. The 1.5 A resolution crystal structure of the anion-assisted dimer of proPLA2 reported in this paper is compared with the corresponding structure for PLA2 [Pan, Y. H., et al. (2001) Biochemistry 40, 609-617]. As a mimic for the forms bound to the anionic interface, these structures provide insights into the possible structural basis for the impaired chemical step of the zymogen. The proPLA2 dimer contained within one crystallographic asymmetric unit has one molecule of the inhibitor 1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol and is bridged by four coplanar sulfate anions. Relative to the structure of PLA2, the subunit contact surface in proPLA2 displays a tilted orientation, an altered mode of inhibitor binding, displacement of a mechanistically significant loop that includes Tyr69, and a critical active site water seen in PLA2 that is not seen in proPLA2. These differences are interpreted to suggest possible origins of the functional differences between the pro and active enzyme at an anionic interface. A structural origin of this difference is discussed in terms of the calcium-coordinated activated water mechanism of the esterolysis reaction. Together, a comparison of the structures of the anion-assisted dimers of PLA2 and proPLA2 not only offers an explanation of why the zymogen form is k(cat)-impaired and binds poorly even to the anionic interface but also supports a mechanism for the activated enzyme that includes a critical second-sphere assisting water bridging His48 and the calcium-coordinated catalytic water.

Animals↗
PubMed2001

A wireless, remote query ammonia sensor.

This paper presents a wireless, remote query ammonia sensor comprised of a free-standing magnetoelastic thick-film coated with a polymer, poly(acrylic acid-co-isooctylacrylate), that changes mass in response to atmospheric ammonia concentration. The mass of the polymer layer modulates the resonant frequency the ferromagnetic magnetoelastic substrate, hence by monitoring the frequency response of the sensor, atmospheric NH3 concentration can be determined remotely, without the need for physical connections to the sensor or specific alignment requirements. The effect of copolymer composition, polymer film thickness, and relative humidity level (RH) on the sensitivity of the sensor were investigated. The sensor linearly tracks ammonia concentration below 0.8 vol.%, and tracks higher concentrations logarithmically; within the linear calibration range, a 0.02 vol.% change in NH3 concentration can be detected.

Acrylates↗
PubMed2001

Regulation of myogenic terminal differentiation by the hairy-related transcription factor CHF2.

We have recently cloned a novel basic helix-loop-helix factor, CHF2, that functions as a transcriptional repressor. To address its role in the regulation of myogenic terminal differentiation, we analyzed its expression pattern during C2C12 mouse myotube formation. In undifferentiated myoblasts, CHF2 is expressed at high levels. After induction of myotube formation in low serum, CHF2 expression is barely detectable at 3 days after induction. Myogenin expression, in contrast, peaks at 3 days. In transiently transfected 10T1/2 embryonic fibroblasts, CHF2 inhibited MyoD-dependent activation of the myogenin promoter in a dose-dependent fashion. Electrophoretic mobility shift analysis indicated that CHF2 inhibits the binding of the MyoD.E47 heterodimer to the E-box binding site. CHF2 also inhibited myogenic conversion of 10T1/2 cells by MyoD, as measured by skeletal myosin heavy chain protein expression. Coimmunoprecipitation analysis indicated that CHF2 forms a protein complex with MyoD. Mutational analysis of CHF2 indicated that the repression activity for both transcription and myogenic conversion mapped to a hydrophobic carboxyl-terminal region and did not require either the basic helix-loop-helix or YRPW motifs. Our data indicate that CHF2 functions as a transcriptional repressor of myogenesis by formation of an inactive heterodimeric complex with MyoD and likely plays an important role in muscle development.

Animals↗
PubMed2001

Five coplanar anion binding sites on one face of phospholipase A2: relationship to interface binding.

We report the structures of the crystallographic dimer of porcine pancreatic IB phospholipase A(2) (PLA2) with either five sulfate or phosphate anions bound. In each structure, one molecule of a tetrahedral mimic MJ33 [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol] and the five anions are shared between the two subunits of the dimer. The sn-2-phosphate of MJ33 is bound in the active site of one subunit (A), and the alkyl chain extends into the active site slot of the second subunit (B) across the subunit-subunit interface. The two subunits are packed together with a large hydrophobic and desolvated surface buried between them along with the five anions that define a plane. The anions bind by direct contact with two cationic residues (R6 and K10) per subunit and through closer-range H-bonding interactions with other polarizable ligands. These features of the "dimer" suggest that the binding of PLA2 to the anionic groups at the anionic interface may be dominated by coordination through H-bonding with only a partial charge compensation needed. Remarkably, the plane defined by the contact surface is similar to the i-face of the enzyme [Ramirez, F., and Jain, M. K. (1991) Proteins: Struct., Funct., Genet. 9, 229-239], which has been proposed to make contact with the substrate interface for the interfacial catalytic turnover. Additionally, these structures not only offer a view of the active PLA2 complexed to an anionic interface but also provide insight into the environment of the tetrahedral intermediate in the rate-limiting chemical step of the turnover cycle. Taken together, our results offer an atomic-resolution structural view of the i-face interactions of the active form of PLA2 associated to an anionic interface.

Animals↗
PubMed2001

Factors controlling the rate of DDE dechlorination to DDMU in Palos Verdes margin sediments under anaerobic conditions.

Marine sediments off the coast of the Palos Verdes Peninsula in California have been designated a Superfund site primarily because of the presence of DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethene]. For decades, it was believed that DDE was not microbially transformed, but anaerobic bacteria in the Palos Verdes sediments reductively dechlorinate DDEto DDMU [1-chloro-2,2-bis(p-chlorophenyl)ethene], which is also found in the sediments. The effects of electron donor to sulfate ratio, available carbon, sampling sites, sediment depth, and temperature on the rate and extent of DDE dechlorination in anaerobic Palos Verdes sediment microcosms were investigated. Dechlorination rates varied, depending on the site and depth from which the sediments were collected, but DDE dechlorination occurred with sediments from all locations studied. Sulfate and low temperatures slowed dechlorination, but in the presence of sulfate and at in situ temperature, the dechlorination rates observed in the microcosms agree well with the observed rate of DDE disappearance from the Palos Verdes margin sediments.

California↗
PubMed2001

Evaluation of an electrochemical bioreactor system in the biotransformation of 6-bromo-2-tetralone to 6-bromo-2-tetralol.

Biotransformation of 6-bromo-2-tetralone (Br-beta-tetralone) to 6-bromo-2-tetralol (Br-beta-tetralol) by yeast cells of Trichosporon capitatum (ATCC 74312) and its partially purified Br-beta-tetralone reductase was evaluated in an electrochemical bioreactor. The biotransformation rates and final product formation were significantly affected by substrate concentration, biomass and electric potential. At 2 g/l of substrate, the initial reaction rate and final product were increased by 35% and 15%, respectively, with -1.5 V of electric potential compared to without electric potential. Additional substrate (2 g/l) provided by pulse feeding to the reaction mixture at different intervals resulted in 2.1 g/l Br-beta-tetralol compared to a total of 1.2 g/l without feeding. However, the increased production was not proportionate to the amount of additionally fed substrate. Increased substrate availability by the addition of 5% (v/v) ethanol resulted in the highest reaction rate and product formation, but addition of ethanol at a concentration higher than 5% decreased the reaction rate. At low biomass, the initial reaction rates were enhanced significantly when electric potential was high, but a higher biomass was necessary to obtain a similar reaction rate when electric potential was reduced. The highest initial reaction rate (59.2 mg/l per min) was achieved with a two-fold biomass concentration of 15.6 g of dry cell weight/l, substrate at 4 g/l and electric potential at -6 V. The conversion of Br-beta-tetralone to Br-beta-tetralol with partially purified Br-beta-tetralone reductase was slow in the presence of electric potential.

Biomass↗
PubMed2001

Dandy-Walker syndrome: different modalities of treatment and outcome in 42 cases.

OBJECTS: Forty-two patients with Dandy-Walker syndrome who were treated with different surgical modalities over a period of 8 years, from 1988 to 1996, at the Sanjay Gandhi Post Graduate Institute of Medical Sciences were reviewed in the present study. METHODS: All the patients presented with hydrocephalus at the time of diagnosis. Association of other CNS anomalies was detected in 9 (22%) patients. Vermian hypoplasia was present in 36 (88%) cases, while cerebellar hypoplasia was documented in 27 (59%) of these patients. The treatment modality for these cases has continued to change in our institution over the years. Initially the ventriculoperitoneal shunt was the treatment of choice and was performed in 28 (66%) patients. Subsequently shunting of the cyst to the peritoneal cavity was performed in 7 (16%) patients. More recently, 3 of our patients were treated by fenestration of the cyst membrane and 4 others (9%), by ventriculocystoperitoneal shunting procedures. In this study the additional insertion of cystoperitoneal shunts was required in 8 (27%) of the 28 patients who had primary ventriculoperitoneal shunt procedures, because of either nonresolution or reappearance of a posterior fossa cyst. Six out of the 7 cases of primary cystoperitoneal shunts required additional ventriculoperitoneal shunt diversion because of persistent ventricular dilatation. In the group of 4 patients with primary ventriculocystoperitoneal shunts, only 1 patient required shunt revision. The patients on whom cyst membrane fenestration was performed required no additional procedures, except for 1 who already had a ventriculoperitoneal shunt in situ. CONCLUSIONS: Therefore, 18 of the total 42 patients could ultimately be made asymptomatic by ventriculocystoperitoneal shunting for one or the other of these reasons.

Cerebellum↗
PubMed2000

Transforming growth factor-beta 1 inhibition of macrophage activation is mediated via Smad3.

Activated macrophages are critical cellular participants in inflammatory disease states. Transforming growth factor (TGF)-beta1 is a growth factor with pleiotropic effects including inhibition of immune cell activation. Although the pathway of gene activation by TGF-beta1 via Smad proteins has recently been elucidated, suppression of gene expression by TGF-beta1 remains poorly understood. We found that of Smad1-Smad7, Smad3 alone was able to inhibit expression of markers of macrophage activation (inducible nitric-oxide synthase and matrix metalloproteinase-12) following lipopolysaccharide treatment in gene reporter assays. Transient and constitutive overexpression of a dominant negative Smad3 opposed the inhibitory effect of TGF-beta1. Domain swapping experiments suggest that both the Smad MH-1 and MH-2 domains are required for inhibition. Mutation of a critical amino acid residue required for DNA binding in the MH-1 of Smad3 (R74A) resulted in the loss of inhibition. Transient overexpression of p300, an interactor of the Smad MH-2 domain, partially alleviated the inhibition by TGF-beta1/Smad3, suggesting that inhibition of gene expression may be due to increased competition for limiting amounts of this coactivator. Our results have implications for the understanding of gene suppression by TGF-beta1 and for the regulation of activated macrophages by TGF-beta1.

Animals↗
PubMed2000

Do membrane-bound enzymes access their substrates from the membrane or aqueous phase: interfacial versus non-interfacial enzymes.

For membrane-bound enzymes that act on substrates that partition between the membrane and aqueous phases, it is possible to imagine two fundamentally different mechanisms. Interfacial enzymes must access their substrate from the membrane phase, in other words substrate in the membrane binds directly to the active site of the enzyme at the membrane without mixing with substrate molecules in the aqueous phase. On the other hand, non-interfacial enzymes, either bound to membranes or present in the aqueous phase, must access their substrates from the aqueous phase, i.e. substrate in the aqueous phase binds directly to the enzyme without mixing with substrates in the membrane phase. An interfacial mechanism for some enzymes including secreted and cytosolic phospholipase A(2) and phosphoinositide 3'-hydroxykinase was rigorously proven by demonstrating that these enzymes processively hydrolyze many phospholipids without desorbing from the surface of vesicles (scooting mode). The non-interfacial mechanism is more difficult to establish because it cannot be addressed by steady-state kinetics. Using a pre-steady-state method in which the enzymatic velocity is measured during the time it takes for substrate to exchange between vesicles, a non-interfacial mechanism was proven for vesicle-bound plasma platelet activating factor acetylhydrolase. This enzyme prefers more water-soluble phospholipids such as those with sn-2 acetyl or oxidatively truncated fatty acyl chains, and this is readily explained by the mandatory access of substrate from the aqueous phase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗