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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 217 records · Page 12Linked to original sources

The odontogenic keratocyst: a 20-year clinicopathologic review.

The odontogenic keratocyst (OKC) is a jaw cyst with a proclivity for local invasion and recurrence. This 20-year retrospective study was conducted to evaluate methods of treatment and recurrence rates. Forty-nine patients were identified with an average age at presentation of 39.5 years. The molar region of either the mandible or maxilla was the principal primary location; the maxillary antrum was also a common site. The majority of cysts were unilocular and associated with adjacent dentition. Initial therapy was typically enucleation with or without extraction of associated teeth; seven cases of recurrent or second primary odontogenic keratocysts required more extensive surgery. Follow-up ranged from 1 to 15 years with an average duration of 4.3 years. The overall recurrence rate was 35%, and the average time to recurrence 4 years. A recurrence rate of 60% was documented for patients with basal cell nevus syndrome or a family history thereof. Long-term follow-up is necessary following initial OKC treatment. The high rate of recurrence in patients with documented or suspected basal cell nevus syndrome suggests the need for more aggressive initial surgical management in this selected patient population.

Adult↗

Association of the Ban I dimorphic site at the human cytosolic phospholipase A2 gene with schizophrenia.

There is evidence of increased phospholipid breakdown in cell membranes of patients suffering from schizophrenia. This may be related to increased levels of the enzyme cytosolic phospholipase A2 (cPLA2) which have been reported in schizophrenic subjects. We have identified a Ban I dimorphic site on the first intron of the cPLA2 gene. Schizophrenic subjects were found to have a significant excess of the A2/A2 homozygote relative to healthy control subjects. Genetically determined alterations in phospholipase activity may thus underlie the reported abnormalities of phospholipid metabolism in schizophrenia.

Cytosol↗

A determinant of substrate specificity predicted from the acyl-acyl carrier protein desaturase of developing cat's claw seed.

Cat's claw (Doxantha unguis-cati L.) vine accumulates nearly 80% palmitoleic acid (16:1Delta9) plus cis-vaccenic acid (18:1Delta11) in its seed oil. To characterize the biosynthetic origin of these unusual fatty acids, cDNAs for acyl-acyl carrier protein (acyl-ACP) desaturases were isolated from developing cat's claw seeds. The predominant acyl-ACP desaturase cDNA identified encoded a polypeptide that is closely related to the stearoyl (Delta9-18:0)-ACP desaturase from castor (Ricinis communis L.) and other species. Upon expression in Escherichia coli, the cat's claw polypeptide functioned as a Delta9 acyl-ACP desaturase but displayed a distinct substrate specificity for palmitate (16:0)-ACP rather than stearate (18:0)-ACP. Comparison of the predicted amino acid sequence of the cat's claw enzyme with that of the castor Delta9-18:0-ACP desaturase suggested that a single amino acid substitution (L118W) might account in large part for the differences in substrate specificity between the two desaturases. Consistent with this prediction, conversion of leucine-118 to tryptophan in the mature castor Delta9-18:0-ACP desaturase resulted in an 80-fold increase in the relative specificity of this enzyme for 16:0-ACP. The alteration in substrate specificity observed in the L118W mutant is in agreement with a crystallographic model of the proposed substrate-binding pocket of the castor Delta9-18:0-ACP desaturase.

Amino Acid Sequence↗

Esophagopericardial fistula arising from Barrett's esophagus.

Esophagopericardial fistula is a rare complication of numerous benign, malignant, and traumatic conditions of the esophagus. Approximately 100 cases of fistulae between the esophagus and heart have been reported. We describe the second reported case of an esophagopericardial fistula secondary to a benign esophageal ulcer within Barrett's mucosa without prior surgery. The radiologic, endoscopic, and surgical management of this case are discussed.

Adult↗

Rapid diagnosis of tuberculosis in various biopsy and body fluid specimens by the AMPLICOR Mycobacterium tuberculosis polymerase chain reaction test.

STUDY OBJECTIVES: This study was undertaken to determine the usefulness of the AMPLICOR Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) test (Roche Diagnostic Systems, Inc; Branchburg, NJ) in diagnosing TB in tissue and body fluid specimens other than respiratory secretions. DESIGN AND SETTING: Prospective analysis of clinical and laboratory data in patients with suspected TB at the four divisional hospitals of Catholic Medical Center, located in New York. PATIENTS AND MEASUREMENTS: A total of 1,090 tissue and body fluid specimens from 1,032 patients with suspected TB were subjected to acid-fast bacillus (AFB) smear, culture, and the AMPLICOR MTB PCR test. RESULTS: Of the 1,090 specimens, 32 grew M tuberculosis complex and 8 specimens grew isolates belonging to the Mycobacterium avium complex (MAC). The AMPLICOR MTB PCR test was positive for 24 of the 32 specimens that grew M tuberculosis. It was also positive for four additional specimens that were culture-negative for M tuberculosis or MAC. Two of these specimens were from patients with a previously recorded positive sputum culture for M tuberculosis. The AMPLICOR test was negative for all eight specimens that yielded MAC only. When AMPLICOR MTB PCR test results were compared with the confirmed clinical diagnosis of TB, the sensitivity, specificity, positive predictive value, and negative predictive value for the AMPLICOR MTB PCR test were 76.4%, 99.8%, 92.8%, and 99.2%, respectively. PCR results were available within 6.5 hours, compared with an average of 3 weeks for culture of M tuberculosis. CONCLUSIONS: These data establish the utility of the AMPLICOR MTB PCR test for the rapid detection of M tuberculosis in tissue and body fluid specimens other than respiratory secretions.

Biopsy↗

Efficacy of topical nonsteroidal drops as pain relief after excimer laser photorefractive keratectomy.

PURPOSE: To compare the efficacy of topical aqueous indomethacin and ketorolac for pain relief following excimer laser photorefractive keratectomy (PRK). METHODS: We conducted a double masked, randomized trial involving 120 patients. All patients received a standard regimen of one of the trial drugs and chloramphenicol ointment to be used four times daily for 2 days. Pain levels and quality were assessed on a 10 cm linear analogue scale prior to each instillation of the topical medication with the McGill pain questionnaire. Pain threshold was evaluated using a modified State Trait Anxiety Inventory questionnaire. Patients were advised to use paracetomol for additional pain relief but were allowed to use any oral analgesic (except nonsteroidal agents) which they documented (type and quantity). RESULTS: There was no significant difference in pain scores between the groups using indomethacin and ketoralac. CONCLUSION: We found no significant difference between topical ketoralac and aqueous indomethacin as pain relief following excimer laser PRK. Both drugs seemed to significantly reduce pain.

Administration, Topical↗

Comparison of 18% ethanol and mechanical debridement for epithelial removal before photorefractive keratectomy.

PURPOSE: To assess the safety of alcohol compared to mechanical debridement for epithelial removal prior to photorefractive keratectomy (PRK). METHODS: Forty-one second eyes of 41 patients underwent epithelial removal using alcohol prior to PRK with a Nidek EC-5000 excimer laser. The results were compared with the results of the 41 first eyes of the same patients that had mechanical debridement. RESULTS: Initial results showed that the alcohol treated group tended to stay slightly hyperopic but had less haze compared to the mechanical debridement group. The treating surgeons favored alcohol as the preferred method of epithelium removal. CONCLUSION: Alcohol debridement is an effective procedure although algorithms may have to be altered to take into account the slightly different healing process postoperatively.

Debridement↗

Satisfaction after photorefractive keratectomy.

PURPOSE: To evaluate patient satisfaction one year after photorefractive keratectomy (PRK) for myopia and myopia astigmatism using the Nidek EC-5000 excimer laser. METHODS: This study assessed the level of satisfaction of 6280 patients who underwent PRK after a minimum follow-up of 1 year. All patients were asked to enter their level of satisfaction as excellent, good, worthwhile, or disappointed into a networked computer database. Their responses were subsequently analyzed according to baseline and postoperative refractive data. RESULTS: Patients considered their results to be as follows: 82.3% good or excellent, 14.9% worthwhile, and 2.8% were disappointed with the outcome. CONCLUSION: A high percentage of patients were satisfied with the outcome following PRK. However, a fair number (14%) of patients considered the treatment to be worthwhile but it did not meet their expectations. Extensive counseling and inculcating realistic expectations before treatment is essential in achieving better patient satisfaction.

Astigmatism↗

Photorefractive keratectomy for myopia with -8.00 diopter cylindrical correction.

PURPOSE: A colleague requested PRK. The last time the patient was seen, no spectacles or contact lenses were worn. However, subjective refraction was -7.00 -5.50 x 165 degrees. The original Nidek nomogram would have suggested setting the laser at the actual refraction. Our algorithm adjustments suggested a 40% extra correction of cylinder would be required. The laser was therefore set to -3.50 -8.00 x 165 degrees aiming for a -1.00 -2.00 x 165 degrees outcome to allow for possible retreatment. METHODS: A 165 micron depth ablation was performed. RESULTS AND CONCLUSION: At 6 weeks after surgery, visual acuity was 0.63 unaided with a refraction of +1.50 -1.75 x 170 degrees on pred forte.

Adult↗

Therapeutic administration of a selective inhibitor of nitric oxide synthase does not ameliorate the chronic inflammation and tissue damage associated with adjuvant-induced arthritis in rats.

Up-regulation of the inducible isoform of nitric oxide synthase (iNOS) was determined during the development of adjuvant-induced arthritis in the rat. iNOS enzymatic activity, measured in spleen tissue, appeared and increased coincidentally with the appearance and degree of paw swelling and joint destruction in this arthritis model, when measured on days 0 through 21 subsequent to inoculation of the rats with adjuvant. The increase in enzymatic activity was paralleled by an increase in the plasma nitrite/nitrate (NOx) level and the appearance of immunoreactive iNOS, as measured by Western immunoblot, in the spleens of these rats. Prophylactic administration of N-iminoethyl-L-lysine (L-NIL) completely abolished iNOS activity (plasma NOx elevation) and effectively reduced both the swelling and radiographic changes in the joint tissues of the noninjected paw measured on day 21. However, therapeutic administration of L-NIL beginning on day 14 had no effect on the inflammatory or arthritic changes measured on day 21, even though plasma NOx levels were reduced to that of the naive controls. These results suggest that iNOS may be involved with the initial stages of the immune response to adjuvant injection, but its product, NO, does not mediate the chronic inflammation and joint destruction which occur during the later phase in this model.

Animals↗

Isolation and characterization of ACC deaminase genes from two different plant growth-promoting rhizobacteria.

We have recently proposed that one way that plant growth-promoting rhizobacteria (PGPR) stimulate plant growth is through the activity of the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase, which causes a lowering of plant ethylene levels resulting in longer roots. As part of an effort to understand the role of this enzyme in PGPR, the genes for ACC deaminase from two PGPR, Enterobacter cloacae CAL2 and UW4, have been isolated. These genes are highly homologous to the ACC deaminase genes from Pseudomonas strains 6G5 and F17 and similar to the ACC deaminase gene from Pseudomonas sp. strain ACP. The region downstream (i.e., at the 3'-terminal end) of the strain UW4 ACC deaminase gene has a potential hairpin-like transcription termination site. The regions upstream of the strains UW4 and CAL2 ACC deaminase genes contain putative ribosome-binding sites; however, the promoter sequences have not yet been identified. Southern hybridization experiments suggest that there is a single copy of the ACC deaminase gene in Enterobacter cloacae strains UW4 and CAL2 and that there may be several different types of ACC deaminase genes in different microbes. The cloned ACC deaminase gene can be expressed in Escherichia coli enabling this bacterium to grow on ACC as a sole source of nitrogen and confers upon both Escherichia coli and Pseudomonas spp. strains that are transformed with this gene the ability to promote the elongation of the roots of canola seedlings.

Amino Acid Sequence↗

In vivo homologous regulation of mu-opioid receptor gene expression in the mouse.

Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in rats and mice following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possibility that in vivo homologous regulation by agonists may not occur. Therefore, in the present study, the effect of a high intrinsic efficacy opioid receptor agonist on opioid receptor density, gene expression and tolerance was determined. Mice were infused with etorphine for 7 days using an osmotic minipump, then the pump was removed and studies conducted 16-168 h later. Etorphine (50-250 microg/kg/day) infusion produced significant dose-dependent tolerance to the analgesic (tailflick) effects of etorphine, as well as dose-dependent mu-opioid receptor downregulation in brain at 16 h following the end of the infusion. Mu-opioid receptor density returned to control levels over a 168 h period following the end of etorphine (250 microg/kg/day) infusion. Similarly, the magnitude of tolerance decreased over the same period. Evaluation of changes in brain mu-opioid receptor mRNA 16 h following etorphine infusion indicated that there was dose-dependent increase in steady-state levels, with no significant change in GAPDH mRNA. The increase in mu-opioid receptor mRNA was approximately 55-65% over control at the highest etorphine infusion dose. Mu-opioid receptor mRNA returned to control levels over a 168 h period following the end of etorphine (250 microg/kg/day) infusion. These data suggest that the increase in mu-opioid receptor mRNA following the termination of etorphine treatment may drive the recovery of mu-opioid receptors. These data are the first demonstration of in vivo homologous regulation of mu-opioid receptor gene expression in the mouse by an opioid receptor agonist that produces tolerance and receptor downregulation.

Analgesics, Opioid↗

Correlation between mutation in P53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin's lymphoma.

In the biology of a cell, the central role of p53 in controlling functions such as G1/S transition (check point) and DNA damage repair, and as a trigger of apoptosis, is well established. Somatic mutations or other changes in P53 have been reported in numerous tumor types, and in some of these, they are associated with poor prognosis. In this study, we examined 237 cytogenetically characterized B-cell non-Hodgkin's lymphomas (B-NHLs) for somatic changes in P53 by Southern blot analysis, by single-strand conformation polymorphism analysis (SSCP) of exon 5 through 9, and by direct sequencing of SSCP variants to determine the frequency and types of mutations and their clinical significance. In a portion of these (173 tumors), we also studied p53 expression by immunostaining. On Southern blots, no gross change was identified in P53 and no mutation was identified in exon 9. In exons 5 through 8, 27 different mutations were identified in 25 patients (23 single-base substitutions, 3 deletions, 1 duplication). Mutations in P53 were identified in 25 of 237 tumors (10.5%), which included 1 of 45 small lymphocytic lymphomas (SLLs), 2 of 38 follicular small cleaved-cell lymphomas (FSCCs), 2 of 35 follicular mixed small cleaved-cell and large-cell lymphomas (FMxs), 1 of 4 follicular large-cell lymphomas (FLCs), 1 of 14 diffuse small cleaved-cell lymphomas (DSCCs), 2 of 17 diffuse mixed small- and large-cell lymphomas (DMxs), and 16 of 84 diffuse large-cell lymphomas (DLCCs); the difference between the histologic groups was significant (P < .01). Among mantle-cell lymphoma (MC) patients, 3 of 10 had mutations. In 16 patients, the mutation was identified in specimens obtained at diagnosis. Mutation of transition type and transversion type occurred at a relative frequency of 2:1. Thirty percent occurred at CpG dinucleotide sequences and the codon for arginine was most frequently affected. Nineteen of 99 tumors with complex cytogenetic abnormalities, but none of 69 tumors with simple cytogenetic abnormalities, had mutations (P < .001). Similarly, 11 of 25 tumors with an abnormality of 17p and 8 of 143 tumors with apparently normal 17p had mutations (P < .0001). Positive correlations were found between a mutation and p53 expression (P < .001), between missense type mutations and p53 expression (P < .005), and between 17p abnormalities and p53 expression (P < .05). Twenty-two of 49 patients without mutation and 14 of 17 patients with mutations died (P < .05), but there was no significant difference in median survival. Similarly, 21 of 26 p53 positive patients died, whereas only 1 of 24 p53-negative patients died on-study (P < .001). Among p53-negative patients, mutation (P < .01) was positively associated with a fatal outcome. These findings indicate that in B-NHL, somatic changes in P53 were present in diagnostic specimens of all histologic types, but at a higher frequency in DLC and MC tumors. P53 mutation and/or expression has a negative influence on survival, and therefore can serve as prognostic indicators. Immunostaining for p53 is an effective way to screen for P53 changes in these tumors.

Amino Acid Sequence↗

Kinase domain of the muscle-specific receptor tyrosine kinase (MuSK) is sufficient for phosphorylation but not clustering of acetylcholine receptors: required role for the MuSK ectodomain?

Formation of the neuromuscular junction (NMJ) depends upon a nerve-derived protein, agrin, acting by means of a muscle-specific receptor tyrosine kinase, MuSK, as well as a required accessory receptor protein known as MASC. We report that MuSK does not merely play a structural role by demonstrating that MuSK kinase activity is required for inducing acetylcholine receptor (AChR) clustering. We also show that MuSK is necessary, and that MuSK kinase domain activation is sufficient, to mediate a key early event in NMJ formation-phosphorylation of the AChR. However, MuSK kinase domain activation and the resulting AChR phosphorylation are not sufficient for AChR clustering; thus we show that the MuSK ectodomain is also required. These results indicate that AChR phosphorylation is not the sole trigger of the clustering process. Moreover, our results suggest that, unlike the ectodomain of all other receptor tyrosine kinases, the MuSK ectodomain plays a required role in addition to simply mediating ligand binding and receptor dimerization, perhaps by helping to recruit NMJ components to a MuSK-based scaffold.

Agrin↗

Microbiological activity of whole and fractionated crude extracts of tea (Camellia sinensis), and of tea components.

Aqueous extracts of teas (Camellia sinensis) of different types and from various sources inhibited a wide range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. Tea extracts were bactericidal to staphylococci and Yersinia enterocolitica at well below 'cup of tea' concentrations. Activity was confined to one of four fractions obtained from a green tea extract by partition chromatography. Testing of pure tea compounds and closely related chemicals suggested that the antibacterial activity of extracts of green tea can be explained by its content of epigallocatechin, epigallocatechin gallate and epicatechin gallate. In black tea extracts, theaflavin and its gallates are additional antibacterially active components.

Anti-Bacterial Agents↗

Value of posterior and right ventricular leads in comparison to the standard 12-lead electrocardiogram in evaluation of ST-segment elevation in suspected acute myocardial infarction.

In this multicenter prospective trial, we studied posterior (V7 to V9) and right ventricular (V4R to V6R) leads to assess their accuracy compared with standard 12-lead electrocardiograms (ECGs) for the diagnosis of acute myocardial infarction (AMI). Patients aged >34 years with suspected AMI received posterior and right ventricular leads immediately after the initial 12-lead ECG. ST elevation of 0.1 mV in 2 leads was blindly determined and inter-rater reliability estimated. AMI was diagnosed by World Health Organization criteria. The diagnostic value of nonstandard leads was determined when 12-lead ST elevation was absent and present and multivariate stepwise regression analysis was also performed. Of 533 study patients, 64.7% (345 of 533) had AMI and 24.8% received thrombolytic therapy. Posterior and right ventricular leads increased sensitivity for AMI by 8.4% (p = 0.03) but decreased specificity by 7.0% (p = 0.06). The likelihood ratios of a positive test for 12, 12 + posterior, and 12 + right ventricular ECGs were 6.4, 5.6, and 4.5, respectively. Increased AMI rates (positive predictive values) were found when ST elevation was present on 6 nonstandard leads (69.1%), on 12 leads only (88.4%), and on both 6 and 12 leads (96.8%; p <0.001). Treatment rates with thrombolytic therapy increased in parallel with this electrocardiographic gradient. Logistic regression analysis showed that 4 leads were independently predictive of AMI (p <0.001): leads I, II, V3, V5R; V9 approached statistical significance (p = 0.055). The standard ECG is not optimal for detecting ST-segment elevation in AMI, but its accuracy is only modestly improved by the addition of posterior and right ventricular leads.

Aged↗

Phosphoinositide binding specificity among phospholipase C isozymes as determined by photo-cross-linking to novel substrate and product analogs.

We tested for the presence of high-affinity phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 binding sites in four phospholipase C (PLC) isozymes (delta1, beta1, beta2, and beta3), by probing these proteins with analogs of inositol phosphates, D-Ins(1,4,5)P3, D-Ins(1,3,4,5)P4, and InsP6, and polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3, which contain a photoactivatable benzoyldihydrocinnamide moiety. Only PLC-delta1 was specifically radiolabeled. More than 90% of the label was found in tryptic and chymotryptic fragments which reacted with antisera against the pleckstrin homology (PH) domain, whereas less than 5% was recovered in fragments that encompassed the catalytic core. In separate experiments, the isolated delta1-PH domain was also specifically labeled. Equilibrium binding of D-Ins(1,4,5)P3 to PLC-delta1 indicated the presence of a single, high-affinity binding site; binding of D-Ins(1,4,5)P3 to PLC-beta1, -beta2, or -beta3 was not detected. The catalytic activity of PLC-delta1 was inhibited by the product D-Ins(1,4,5)P3, whereas no inhibition of PLC-beta1, -beta2, or -beta3 activity was observed. These results demonstrate that the PH domain is the sole high-affinity PI(4,5)P2 binding site of PLC-delta1 and that a similar site is not present in PLC-beta1, -beta2, or -beta3. The data are consistent with the idea that the PH domain of PLC-delta1, but not the beta isozymes, directs the catalytic core to membranes enriched in PI(4,5)P2 and is subject to product inhibition.

Benzophenones↗