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Biomedical subjects

N Mehta

Publications and source records attributed to N Mehta.

At least 19 recordsLinked to original sources
PubMed2001

Effect of various alkyl and unsaturated substituents on the mutagenicity of some nitrophenyl thioethers.

A variety of nitro-substituted phenyl alkyl/aryl thioethers and nitroso-substituted phenyl alkyl/aryl thioethers have been synthesized and tested for their mutagenicity towards Salmonella typhimurium strain TA100, TA98, TA98NR and TA98/1,8-DNP(6) in the absence of S9 mix. The relative order of mutagenicity in TA98 and TA100 among p-nitrophenyl thioethers having alkyl or aryl substituents is allyl>phenyl>benzyl>butyl>propyl>ethyl>methyl. Compounds having an alkyl chain C(6) to C(12) were found to be non-mutagenic. Among the various positional isomers (ortho, meta and para) of nitro-substituted diphenyl thioethers only the compounds having the -NO(2) function at the para position is mutagenic, whereas compounds having a -NO(2) function at ortho and meta are non-mutagenic. However, the reduced intermediate, ortho-nitroso derivative was found to be mutagenic in all the four strains but the meta-nitroso derivative was found to be non-mutagenic. All mutagens were found to be non-mutagenic when tested in nitroreductase deficient strain TA98NR, whereas their nitroso intermediates are found to be mutagenic. A substantial fall in the mutagenic activity is observed when some mutagens are tested in O-acetyltransferase deficient strain TA98/1,8-DNP(6).

Mutagenicity Tests↗
PubMed2001

Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli.

BACKGROUND: Aldolases are carbon bond-forming enzymes that have long been identified as useful tools for the organic chemist. However, their utility is limited in part by their narrow substrate utilization. Site-directed mutagenesis of various enzymes to alter their specificity has been performed for many years, typically without the desired effect. More recently directed evolution has been employed to engineer new activities onto existing scaffoldings. This approach allows random mutation of the gene and then selects for fitness to purpose those proteins with the desired activity. To date such approaches have furnished novel activities through multiple mutations of residues involved in recognition; in no instance has a key catalytic residue been altered while activity is retained. RESULTS: We report a double mutant of E. coli 2-keto-3-deoxy-6-phosphogluconate aldolase with reduced but measurable enzyme activity and a synthetically useful substrate profile. The mutant was identified from directed-evolution experiments. Modification of substrate specificity is achieved by altering the position of the active site lysine from one beta strand to a neighboring strand rather than by modification of the substrate recognition site. The new enzyme is different to all other existing aldolases with respect to the location of its active site to secondary structure. The new enzyme still displays enantiofacial discrimination during aldol addition. We have determined the crystal structure of the wild-type enzyme (by multiple wavelength methods) to 2.17 A and the double mutant enzyme to 2.7 A resolution. CONCLUSIONS: These results suggest that the scope of directed evolution is substantially larger than previously envisioned in that it is possible to perturb the active site residues themselves as well as surrounding loops to alter specificity. The structure of the double mutant shows how catalytic competency is maintained despite spatial reorganization of the active site with respect to substrate.

Aldehyde-Lyases↗
PubMed2001

Twenty-nine years after carbon monoxide intoxication.

Carbon monoxide (CO) is a worldwide environmental toxin and a leading cause of deliberate or accidental poisoning. There is an extensive literature devoted to the clinical features and treatment of those victims who have survived acute CO poisoning for a short length of time. The long-term sequelae of non-fatal poisoning have received scanty references, and the prospects for the long-lasting survivors of acute CO intoxication are less clear. Literature review uncovered reports of only three patients who were followed for a considerable period of time. We present a case of CO poisoning with progressive neurological and psychological deterioration that began 17 years after recovery from a severe, accidental CO asphyxia. The patient was examined in the neurology out patient clinic 29 years after the initial CO intoxication. We believe the unique status of this patient, her similarity to one other case in the literature and the circumstances allowing correlation of the clinical picture to the CO poisoning warrants emphasis.

Adult↗
PubMed2001

Comparison of the effects of a cell saver and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing valve surgery.

OBJECTIVE: To compare 2 important techniques of blood conservation, use of a cell saver and low-dose aprotinin, in terms of blood loss and homologous blood usage in patients undergoing cardiac valve surgery. DESIGN: Prospective, randomized. SETTING: Tertiary care hospital. PARTICIPANTS: Sixty adult patients undergoing elective valve surgery. INTERVENTIONS: The patients were divided into 3 groups of 20 each. In group 1, aprotinin in the dose of 30,000 KIU/kg was added to the pump prime, with a further dose of 15,000 KIU/kg added at the end of each hour of cardiopulmonary bypass. In group 2, a cell-saver system was used to collect all blood at the operation site for processing in preparation for subsequent reinfusion. Group 3 patients acted as a control group and underwent routine management, which included collection of autologous blood during the pre-cardiopulmonary bypass period. A hemoglobin of <8 g/dL was considered as an indication for bank blood transfusion in the postoperative period. MEASUREMENTS AND MAIN RESULTS: The chest tube drainage was significantly less in group 1 compared with groups 2 and 3, with total drainage (median [interquartile range]) amounting to 250 mL [105 to 325 mL] vs. 700 mL [525 to 910 mL] in group 2 and 800 mL [650 to 880 mL] in group 3 (p < 0.001). The patients in groups 1 and 2 required significantly less bank blood (median [interquartile range]) as compared with group 3 (350 mL [0 to 525 mL], 350 mL [0 to 350 mL], and 1050 mL [875 to 1050 mL]; p < 0.001), respectively. Cell saver provided 410 +/- 130 mL of hemoconcentrated blood in group 2. The average preoperative hemoglobin concentration was 11.3 g/dL, and it was around 9 g/dL on the 7th postoperative day. The hemoglobin concentration at various stages during hospitalization in all 3 groups was similar. CONCLUSIONS: Low-dose aprotinin and a cell saver are effective and comparable methods of blood conservation. Aprotinin helps by decreasing the postoperative drainage, and a cell saver helps by making the patient's own blood available for transfusion.

Adult↗
PubMed2001

Mandibular deviations in TMD and non-TMD groups related to eye dominance and head posture.

This study was designed to determine whether eye-dominance affects head posture (rotation) and in turn, whether head posture is associated with mandibular frenum midline deviation, in both TMJ and control subjects. Eye dominance was determined using three tests: Porta, Hole, Point tests. Natural head posture was evaluated using the Arthrodial protractor. Mandibular frenum deviation was recorded as left, right or no deviation. Fifty female subjects were included in the study, 25 TMJ patients attending the Gelb Craniomandibular Pain Center and 25 non-TMJ control subjects. The findings indicate that eye dominance and direction of head rotation are strongly associated in both TMJ and control subjects. Further, in TMJ subjects mandibular deviation occurred in greater frequency than in controls and tends to occur in the contra lateral direction of head rotation.

Adult↗
PubMed2001

Finding evidence-based answers to clinical questions online.

You can find evidence-based answers to clinical questions quickly by searching online medical databases. The key is to be selective, on the basis of the type of information you need. Online textbooks, consensus guidelines systematic reviews, and MEDLINE are all available.

Directories as Topic↗
PubMed2000

Management and prevention of meningococcal disease.

While many other illnesses affecting children have been contained or even eliminated, meningococcal disease has become a leading infectious cause of death. The major management challenge may be increased intracranial pressure or toxic shock, depending on whether meningitis or septicemia predominates. A new protein-conjugated group C vaccine is expected to reduce deaths by as much as 40%.

Adolescent↗
PubMed2000

Mutagenicity studies of FAVOR PAC.

A series of in vitro and in vivo assays have been conducted using FAVOR PAC (CAS Registry No. 9003-04-7), a cross-linked sodium polyacrylate polymer, to test its ability to induce mutations. FAVOR PAC is a member of the FAVOR family of superabsorbent polymers (SAPs) developed by Stockhausen GmbH & Co KG (Krefeld, Germany). These SAPs are known for their ability to retain large volumes of fluid, even against pressure. The genotoxic potential of FAVOR PAC and its extracts was examined in the following five standard mutagenicity assays: the Salmonella typhimurium and Escherichia coli reverse mutation assay, the mouse lymphoma fluctuation assay, the mouse lymphoma forward mutation assay, the in vivo mouse micronucleus assay, and an in vitro rat DNA synthesis assay. Based on the results of these assays, it was concluded that FAVOR PAC was clearly not genotoxic under any of the conditions of the mutagenicity assays performed.

Acrylic Resins↗
PubMed2000

Pancreaticoduodenectomy for metastatic renal cell carcinoma: report of a case.

Metastasis to the pancreas from a distant primary cancer is uncommon, most cases being detected in the advanced stages of disease, often multiple in number, and diffusely displayed beyond surgical salvage. A solitary metastasis in the head of the pancreas is rarely encountered and although potentially amenable to surgical resection, surgeons are hesitant to perform pancreaticoduodenectomy for metastatic disease. Renal cell carcinoma is one malignancy with a propensity to metastasize to the pancreas. We report herein the case of a solitary pancreatic metastasis from renal cell carcinoma successfully treated by pancreaticoduodenectomy in a middle-aged man. A discussion on the indications and effectiveness of performing pancreaticoduodenectomy for metastatic renal cell carcinoma is also presented.

Carcinoma, Renal Cell↗
PubMed2000

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

BACKGROUND/AIMS: Human milk fortification has been advocated to enhance premature infants' growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. METHODS: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. RESULTS: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 +/- 2.1 vs. 144.4 +/- 2.5 ml/kg/day, mean +/- SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 +/- 1.3 and 20.4 +/- 1.2 g/day, p < 0.05; head circumference 1.0 +/- 0.1 and 0.8 +/- 0.1 cm/week; length 0.9 +/- 0.1 and 0.8 +/- 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. CONCLUSIONS: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Body Height↗
PubMed2000

Disposable versus reusable biopsy forceps for colorectal epithelial cell proliferation in humans.

The performance of various measures of rectal mucosal proliferation has been evaluated in the literature, but the performance of the forceps used to obtain the tissue has received little attention. We used data from two large studies of proliferation at a single institution to compare reusable and disposable endoscopic forceps. Endoscopic pinch biopsies were taken 10 cm from the anal verge using either reusable or disposable, oval-cupped, sheathed forceps. The specimens were fixed, embedded, and sectioned, taking care to orient the specimens longitudinally. Five sections were placed on each slide. We determined how many slides did not contain eight scorable crypts (inadequate) and how many sections were necessary to identify eight complete crypts. There were 395 subjects who had biopsies taken with reusable forceps and 185 subjects who had biopsies taken with disposable forceps. The specimens were inadequate in 27.6% of the reusable forceps specimens versus 2.7% of the disposable forceps (P < 0.0001). The mean number of tissue sections necessary to identify eight scorable crypts for the reusable forceps was 3.82 (SD, 0.87) compared with 3.17 (SD, 0.83) for disposable forceps (P = 0.0001). The specimens taken with the disposable forceps were better, probably because the forceps were sharper. We believe that the better quality of the specimens and the sterility justify the higher cost of disposable forceps. We would urge investigators in proliferation studies to evaluate the biopsy equipment as carefully as they evaluate other aspects of their methods.

Biopsy↗
PubMed1999

alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.

alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.

14-3-3 Proteins↗