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Biomedical subjects

A Mehta

Publications and source records attributed to A Mehta.

At least 55 records · Page 3Linked to original sources
PubMed2002

Attenuation of ischemia/reperfusion induced MAP kinases by N-acetyl cysteine, sodium nitroprusside and phosphoramidon.

Ischemia followed by reperfusion has a number of clinically significant consequences. A number of pathophysiological processes appear to be involved in ischemia/reperfusion (I/R) injury. The mitogen activated protein kinases (MAPK) are integral components of the parallel MAP kinase cascades activated in response to a variety of cellular stress inducing ischemia/ATP depletion and inflammatory cytokines. Many studies suggest that members of the MAP kinase family in particular Jun N-terminal kinase (JNK) are activated in kidney following ischemia/reperfusion of this tissue. The present study underlines the therapeutic potential of the combination of N-acetyl cysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor and phosphoramidon (P), an endothelin-1 converting enzyme inhibitor in ameliorating the MAPK induced damage during renal ischemia/reperfusion injury. Our previous results showed that 90 min of ischemia followed by reperfusion caused very severe injury and that the untreated animals had 100% mortality after the 3rd day whereas there was improved renal function and 100% survival of animals in the three drug combination treatment group. The present study, mainly on tissue sections, further supports the protection provided by the triple drug therapy. A higher degree of expression of all the three classes of MAPK, i.e. JNK, P38 MAP kinases and P-extracellular signal regulated kinases (ERKs) can be seen in kidneys subjected to ischemia/reperfusion insult. Pretreatment with a combination of N-acetyl cysteine, sodium nitroprusside, and phosphoramidon completely inhibits all three classes of MAPK and ameliorates AP-1 whereas individual or a combination of any two drugs is not as effective.

Acetylcysteine↗
PubMed2002

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants.

BACKGROUND: Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. OBJECTIVE: To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. PATIENTS: The 2,046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. METHODS: Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. RESULTS: We identified 33 cases of IA (28% disseminated) in 2,046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1,000 patient-years (33 cases/6,813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1,000-pt year vs. heart 0.4% (3/686) or 1.4 per 1,000-pt year vs. liver 0.7% (3/439) or 2.1 per 1,000-pt year vs. renal 0.4% (3/733) or 1.2 per 1,000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). CONCLUSIONS: The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.

Adult↗
PubMed2002

New developments in the management of Anderson-Fabry disease.

Anderson-Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriasylceramide throughout diverse cells, tissues and organs of the body. The disease usually presents in childhood, is progressive, and results in increasing disability and premature death. Female carriers tend to be less severely affected. AFD is difficult to diagnose because of its heterogeneous signs and symptoms. Awareness is low among health professionals, and diagnosis is typically delayed for several years after first presentation. Treatment was formerly entirely symptomatic, but enzyme replacement therapy has recently been licensed and management is evolving from genetic counselling and palliative care to early diagnosis and active intervention.

Adolescent↗
PubMed2001

Three-dimensional photonic "molecules" from sequentially attached polymer-blend microparticles.

We report the observation of 3D linear or branched chains of polymer-blend microspheres generated from liquid droplets of solution where the modified surface structure of the polymer composite results in highly robust interparticle bonds. Using a linear quadrupole to precisely position particles in space, we are able to take advantage of this novel material property to actively assemble particles in programmable three-dimensional architectures. The robust interlocking nature of interparticle linkage gives rise to strongly coupled morphology-dependent resonances in bisphere and trisphere systems, suggesting the possibility of three-dimensional photonic "molecules" and microscale optical manipulation applications.

Journal Article↗
PubMed2001

Nature of e(g) electron order in La(1-x)Sr(1+x)MnO(4).

X-ray scattering measurements of the low-temperature structure of La(1-x)Sr(1+x)MnO(4) ( 0.33< or =x< or =0.67) indicate the existence of three distinct regions: a disordered phase (x<0.4), a charge-ordered phase (x> or =0.5), and a mixed phase (0.4< or =x<0.5). For x>0.5, the modulation vector associated with the charge order is incommensurate with the lattice and depends linearly on the concentration of e(g) electrons. The primary superlattice reflections are strongly suppressed along the modulation direction and the higher harmonics are weak, implying the existence of a largely transverse and nearly sinusoidal structural distortion, consistent with a charge-density wave of the e(g) electrons.

Journal Article↗
PubMed2001

Nucleoside diphosphate kinase--a component of the [Na(+)]- and [Cl(-)]-sensitive phosphorylation cascade in human and murine airway epithelium.

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl(-)] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na(+)] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl(-) dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl(-)-free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K(+) channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

Adenosine Triphosphate↗
PubMed2001

Endomorphin-1: induction of motor behavior and lack of receptor desensitization.

The endomorphins are recently discovered endogenous agonists for the mu-opioid receptor (Zadina et al., 1997). Endomorphins produce analgesia; however, their role in other brain functions has not been elucidated. We have investigated the behavioral effects of endomorphin-1 in the globus pallidus, a brain region that is rich in mu-opioid receptors and involved in motor control. Bilateral administration of endomorphin-1 in the globus pallidus of rats induced orofacial dyskinesia. This effect was dose-dependent and at the highest dose tested (18 pmol per side) was sustained during the 60 min of observation, indicating that endomorphin-1 does not induce rapid desensitization of this motor response. In agreement with a lack of desensitization of mu-opioid receptors, 3 hr of continuous exposure of the cloned mu receptor to endomorphin-1 did not diminish the subsequent ability of the agonist to inhibit adenylate cyclase activity in cells expressing the cloned mu-opioid receptor. Confirming the involvement of mu-opioid receptors, the behavioral effect of endomorphin-1 in the globus pallidus was blocked by the opioid antagonist naloxone and the mu-selective peptide antagonist Cys(2)-Tyr(3)-Orn(5)-Pen(7) amide (CTOP). Furthermore, the selective mu receptor agonist [d-Ala(2)-N-Me-Phe(4)-Glycol(5)]-enkephalin (DAMGO) also stimulated orofacial dyskinesia when infused into the globus pallidus, albeit transiently. Our findings suggest that endogenous mu agonists may play a role in hyperkinetic movement disorders by inducing sustained activation of pallidal opioid receptors.

Animals↗
PubMed2001

An acidic motif retains vesicular monoamine transporter 2 on large dense core vesicles.

The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of the vesicular monoamine transporter VMAT2 to LDCVs. We now find that a cluster of acidic residues including two serines phosphorylated by casein kinase 2 is required for the localization of VMAT2 to LDCVs. Deletion of the acidic cluster promotes the removal of VMAT2 from LDCVs during their maturation. The motif thus acts as a signal for retention on LDCVs. In addition, replacement of the serines by glutamate to mimic phosphorylation promotes the removal of VMAT2 from LDCVs, whereas replacement by alanine to prevent phosphorylation decreases removal. Phosphorylation of the acidic cluster thus appears to reduce the localization of VMAT2 to LDCVs by inactivating a retention mechanism.

Amino Acid Motifs↗
PubMed2001

Differentially expressed proteins in the interaction of Xanthomonas axonopodis pv. citri with leaf extract of the host plant.

The present study reports the expression of proteins of Xanthomonas axonopodis pv. citri in response to different growth conditions. The bacterium was cultured in the basal medium MM1 and in the presence of leaf extracts from a susceptible host plant (sweet orange) as well as a resistant (ponkan) and a nonhost plant (passion fruit). The protein profiles were analyzed by two-dimensional gel electrophoresis (2-DE). Twelve differential spots (induced, up- and down-regulated and repressed) were observed in the protein profiles of the bacterium cultivated in citrus extract (susceptible host) when compared to that of MM1. The 2-DE profile of the bacterium cultured in the complex medium nutrient yeast glycerol was also obtained and the comparison with that of MM1 revealed 36 differential spots. Five proteins from the different treatments were successfully N-terminally sequenced and the putative functions were assigned by homology searches in databases. Two constitutively expressed proteins, B4 and B5, were identified as pseudouridine synthase and elongation factor P, respectively. The large subunit of ribulose 1,5-biphosphate carboxylase/oxygenase and a sulfate binding protein were found as specifically up-regulated in the presence of citrus extracts. Finally, the heat shock protein G was found exclusively in the complex medium and repressed in all other media.

Bacterial Proteins↗
PubMed2001

Growth inhibition and differentiation of C6 glioma cells on treatment with hmba.

HMBA, a differentiation inducer belonging to the class of hybrid polar compounds, is known to induce terminal differentiation of a number of leukemic and solid tumour cell lines. In this report we have shown that HMBA markedly inhibits growth of C6 glioma cells at non-cytotoxic concentrations ranging from 2.5 m m to 10 m m in a dose-dependent manner. The growth inhibitory effect can be detected as early as 18--24 h. By the sixth day the growth inhibition decreases at all the concentrations tested. Treatment with HMBA results in an accumulation of C6 cells in G0/G1 phase along with a decrease in the number of cells in S phase. HMBA induces morphological differentiation of C6 cells and increases expression of glial fibriliary acidic protein (GFAP), a marker for mature astrocytes. HMBA induces c-fos and represses cycloheximide-induced c-jun and fra-1 expression. HMBA-induced growth inhibition of C6 cells is accompanied by a decrease in Cdk4 protein levels. However, HMBA fails to sustain low Cdk4 levels, which may be responsible for HMBA's failure to sustain the growth inhibitory effect.

Acetamides↗
PubMed2001

Increased m-CPP-induced oral dyskinesia after lesion of serotonergic neurons.

Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)piperazine (m-CPP) produces abnormal orofacial movements in rats. We have previously shown that this behavior is mediated by 5-HT(2C) receptors in the subthalamic nucleus [Neuroscience 72 (1996) 117]. The present studies examined this effect after serotonin depletion to determine whether removal of endogenous serotonin affected this behavioral response and/or subthalamic 5-HT(2C) receptors. Rats received an intraventricular infusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/10 ml) or vehicle after desipramine pretreatment (25 mg/kg ip). The efficacy of serotonin depletion was confirmed by a decrease in serotonin uptake sites measured by autoradiography. Oral dyskinesia induced by peripheral administration of m-CPP (1.0 mg/kg ip) was markedly increased in lesioned rats compared to sham-operated controls 4 and 8 but not 12 days after the lesion. A subset of lesioned rats that displayed transient seizures after m-CPP injection did not prevent the measurement of oral dyskinesia during the observation period. No differences in 5-HT(2C) receptor levels were found with ligand-binding autoradiography in the subthalamic nucleus, or in other brain regions that express this receptor, in rats sacrificed 5 days following 5,7-DHT lesions. The data indicate that lesion of serotonergic neurons in adult rats induces a transient increase in motor responses mediated by subthalamic 5-HT(2C) receptors. These data suggest that functional alterations in serotonergic transmission in the subthalamic nucleus may be involved in the pathophysiology of hyperkinetic movement disorders.

5,7-Dihydroxytryptamine↗
PubMed2001

Possible role of metal redistribution, hepatotoxicity and oxidative stress in chelating agents induced hepatic and renal metallothionein in rats.

A study was planned to investigate possible role of oxidative stress, hepato- and nephrotoxicity and essential metal redistribution following administration of amino and thiol chelating agents on hepatic and renal metallothionein (MT) and the levels of some metalloenzymes in male rats. Animals were administered 50 mg/kg, intraperitoneally, twice daily for 15 consecutive days; a dose of three amino and four thiol chelators and were sacrificed 24 h after the last dose. The results indicate no evidence of oxidative stress in hepatic and renal tissues of rats administered thiol and amino chelators, except for some marginal changes in the animals treated with calcium disodium ethylenediaminetetraacetic acid (EDTA) and D-penicillamine (DPA). Redistribution of essential metal (particularly zinc), hepato- and nephrotoxicity seems to play a significant role in influencing the MT induction by amino chelators. Redistribution of essential metals may also be playing a significant role in a number of metalloenzymes, especially by amino chelators compared to thiol chelators. It can thus be concluded that toxic effects of chelating agents, including metal redistribution and hepatotoxicity, might be playing a crucial role in the metallothionein induction.

Alanine Transaminase↗
PubMed2001

Preparing medical students for a filmless environment: instruction on the preparation of electronic case presentations from PACS.

RATIONALE AND OBJECTIVES: As the use of picture archiving and communication systems (PACS) expands and radiology departments become increasingly filmless, it will become increasingly necessary to teach physicians how to use PACS and download diagnostic images. The authors developed an instruction method in which medical students enrolled in a radiology clerkship were taught how to use the PACS, download digital images, and incorporate them into an electronic case presentation. The feasibility and potential benefits of this instructional method were studied prospectively. MATERIALS AND METHODS: Between June and October 1999, all 36 medical students enrolled in Harvard Medical School's core radiology clerkship at Massachusetts General Hospital, Boston, were required to give an electronic radiology case presentation with images downloaded from the departmental PACS. They were taught how to download images, edit them, and then import them into PowerPoint software. They were also given access to the hospital information system to obtain pertinent clinical information. At the formal presentations, the images were displayed with a liquid crystal display (LCD) projector. The students were surveyed on the Ist and last days of the clerkship regarding their learning experiences. RESULTS: Before the radiology clerkship, 81% of the students had never given an electronic presentation with computer and LCD projector, 83% had no PACS experience, and 56% had no PowerPoint experience. All students learned to prepare and deliver electronic presentations of radiologic cases downloaded from PACS. Their presentations were informative, innovative, and entertaining, and the images were well displayed. The students praised the instruction highly and thought their new skills would serve them well. CONCLUSION: Teaching medical students how to prepare and deliver electronic presentations of radiologic cases downloaded from PACS proved to be very feasible and well appreciated by the students.

Data Display↗
PubMed2001

Evaluating medical students on radiology clerkships in a filmless environment: use of an electronic test prepared from PACS and digital teaching collection images.

RATIONALE AND OBJECTIVES: The competency of medical students in radiology clerkships is traditionally evaluated with film images, projected slides of photographed films, or printed reproductions of films. As radiology departments switch to filmless imaging, it seemed appropriate to determine the feasibility of an electronic evaluation prepared directly from digital images. MATERIALS AND METHODS: The image-based portion of a multiple-choice final examination was prepared as a PowerPoint presentation that included images downloaded from the departmental picture archiving and communication system (PACS) or digital teaching collections. The images were downloaded as bitmap files, imported to Adobe Photoshop for image editing, converted to tagged image file format, and finally imported to PowerPoint, where they were combined with text to create 50 questions. A liquid crystal diode projector displayed the questions, with a timer set to advance them automatically. RESULTS: The examination was easy and inexpensive to prepare (no photography costs). In an initial survey of 25 students, 17 (71%) of 24 students rated the resolution of images as excellent and five (21%) as good. No student gave an image a poor rating. Students preferred that images cover at least 40%-50% of the slides, and most approved of a blue background. An original allowance of 30 seconds per slide was reported to be too fast; the interval was increased to 45 seconds. CONCLUSION: An electronic final examination for medical students, prepared with images downloaded from PACS or digital teaching collections, is feasible, easy to prepare, and cost-effective, and it provides an excellent display of test images.

Clinical Clerkship↗