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S Shah

Publications and source records attributed to S Shah.

At least 325 records · Page 18Linked to original sources
PubMed1993

Assessment of relative risk of second primary tumors after ovarian cancer and of the usefulness of double primary cases as a source of material for genetic studies with a cancer registry.

BACKGROUND: It now is accepted that a small proportion of people with certain forms of cancer have a dominantly inherited gene fault that predisposes them to it. This is more likely with an early age at onset or when the person has had multiple primary tumors. METHODS: Population-based data from the North West Regional Cancer Registry of England regarding 4157 ovarian cancer cases diagnosed between 1980 and 1989 were analyzed to determine the relative risks (RR) of second primary breast and colorectal carcinomas. RESULTS: Elevated risks approaching significance were observed for breast and colorectal carcinoma subsequent to ovarian cancer. After stratification into groups for ovarian histopathologic characteristics and age at onset, significantly elevated risks were obtained for both breast and colorectal tumors after ovarian carcinoma for women younger than 60 years of age at onset and with serous histopathologic characteristics (breast RR, 2.68, P < 0.05; colorectal RR, 4.25, P < 0.05). CONCLUSIONS: These results emphasize the need for greater awareness of the possibility of development of additional cancer after ovarian carcinoma in high-risk groups. Overall, the study supports the theory that breast, colorectal, and ovarian tumors are related genetically.

Adult↗
PubMed1993

HLA-DQ, DR and complement C4 variants in systemic lupus erythematosus.

We have defined HLA-DQA, DQB, DR and complement C4 variants in 92 subjects with SLE and 73 controls. Subjects with SLE showed an increased frequency of HLA-DQA*0501 (P < 0.01 corrected, odds ratio (OR) = 4.97; 95% C.I. = 2.52-9.81), DR3 (P < 0.001, OR = 3.18; 95% C.I. = 1.67-6.04) and C4A*Q0 (P < 0.05, OR = 1.91; 95% C.I. = 0.999-3.65) vs controls. These increases were particularly marked in those subjects positive for antibodies to both Ro and La. HLA-DQB*0501 (P < 0.01 corrected, OR = 0.03), DQA*0101 (P = 0.0012 uncorrected, OR = 0.23) and DR7 (P = 0.0018 uncorrected, OR = 0.28) were decreased in frequency in SLE. SLE patients with disease onset prior to age 30 yr were more likely to possess a DR3-bearing haplotype (P < 0.05 corrected) than those with onset after age 30 yr. No significant associations were found in patients with circulating antibodies to double-stranded DNA, Ro alone, U1 RNP, Sm or in those SLE patients with renal disease or vasculitis. The different associations found in different clinical and immunological subsets of SLE support the concept that SLE contains a variety of immunogenetic subgroups. Analysis of the associations between SLE and DR3, DQA*0501 and C4A*Q0 using the empirical logistic test suggests that the association of SLE with HLA-DQA*0501 is likely to be primary to the associations with both DR3 and C4A*Q0 (P < 0.001). Our results therefore raise the possibility that genes within the HLA-DQ region may have a direct effect upon susceptibility to SLE.

Adolescent↗
PubMed1993

Power comparison of various sibship tests of association.

There are several tests available for use with family studies to test if there is significant evidence of association with a particular disease gene locus, especially of HLA. We have used large simulations to compare the powers of tests using criteria N, R, T, PR, WP and some new tests involving both affecteds and unaffecteds in a sibship. It was found that tests using both affected and unaffected siblings were often more powerful.

Genetic Diseases, Inborn↗
PubMed1993

Insulin and islet cell autoantibodies as time-dependent covariates in the development of insulin-dependent diabetes: a prospective study in relatives.

Using time-dependent methods, the temporal relationships between the detection of insulin and islet cell autoantibodies and the onset of insulin dependent diabetes (IDDM) were analyzed in a prospective study of 4694 nondiabetic relatives of 1929 patients with IDDM who had been followed for a median of 4 yr. Insulin autoantibodies were detected in 1.5% of relatives at their initial test whereas an additional 1.0% subsequently became positive for these antibodies during follow-up. Islet cell autoantibodies were detected in 2.6% of the relatives at the time of their first test and an additional 0.9% were observed to develop them during the follow-up period. The risk of developing IDDM was significantly higher (P = 0.0001) among those who were found to have one of these antibodies, but was highest among those under the age of 20 yr at inception of this study who tested positive for both. Among older relatives, the detection of insulin autoantibodies among those who were islet cell antibody positive did not convey an additional risk of IDDM. In a subset of relatives, the presence of either antibody was associated with a higher frequency (P < 0.001) of diabetes associated human leukocyte antigen-DR 3/4 heterozygotes. Islet cell autoantibodies were highly associated with elevated fasting and 60-min glucose concentrations (P = 0.0001) as well as decreased early phase (1 and 3 min) insulin response to an iv glucose tolerance test (P = 0.0001). Insulin antibodies were significantly associated with decreased early phase insulin response to iv glucose (P = 0.0003). These data confirm independent risks associated with each antibody and suggest that their temporal relationship may be an important reflection of the pathogenic process underlying IDDM observations which facilitate its predictability.

Adolescent↗
PubMed1993

A comparison of two registration techniques for digital subtraction radiography.

The dental radiograph is a diagnostic tool that is used to view internal structures without any invasive procedures. A difference radiograph, i.e. one showing the changes that occurred over time, is the best tool for diagnosing slow or small changes. The difficulty in creating a meaningful difference radiograph, or its digital image, is that the imaging geometry of the image pair must be identical. This paper addresses the problem of reproducing imaging geometry. A new technique for registering digital images of radiographs based on the correspondence of 3D anatomical structures (such as root apices and the cemento-enamel junction) was compared with a registration method using occlusal stents. In a pilot study of 30 volunteers, difference images were created by three different registration techniques (no registration, mathematical methods and occlusal stents). The standard deviations of the difference images were used to compare the registration techniques. The results show that this new mathematical technique applied to digital images of radiographs can be used to establish correspondence between pairs of clinical images taken at different projection angles and to produce reconstructed images comparable with images taken with occlusal stents.

Adult↗
PubMed1993

Sphingosines: antimicrobial barriers of the skin.

Among the factors that control the survival of microorganisms on human stratum corneum are skin lipids, including sphingosines. Because the antibacterial spectrum of sphinganine resembles that of cell wall antibiotics, electron microscopy of sphinganine-treated and untreated S. aureus was performed; the lipid induced multiple lesions of cell wall, membrane evaginations and loss of ribosomes. However, comparisons of minimal inhibitory concentration of sphinganine for coccal forms and L-forms of S. aureus, which lack cell walls, and of the respective dose-related reductions in colony-forming units demonstrated both the susceptibility of L-forms and their superior resistance. Therefore, cell wall lesions are sequelae of a probable membrane reaction. Candida albicans was susceptible to sphinganine, sphingosine, dimethylsphingosine, and to a lesser degree, stearylamine. Liquid assays of these lipids against Trichophyton mentagrophytes, T. tonsurans and Epidermatophyton floccosum established their high susceptibility to sphingosine and stearylamine. Sphinganine was the least effective, perhaps due to the presence of L isomers; T. tonsurans was the most sensitive. These four lipids were found to be fungistatic, preventing germination and retarding thalli. Antifungal efficacy was confirmed in vitro on stratum corneum.

Adult↗
PubMed1993

Characterization of fluid distribution through a porous substrate under dynamic g conditions.

Dedicated electronic hardware has been constructed to monitor fluid distributions inside a plant rooting/nutrient substrate (Rockwool). With this hardware the effect of dynamically varying gravity states, from enhanced 2g to reduced 0.01g, on solution distributions inside a cube of substrate was monitored aboard the NASA KC-135 reduced gravity research aircraft. The 8 vertices and the center of the cube were used to place sinusoidal voltage sources (electrodes), emitting different fixed frequencies, inside the substrate. Using another set of 9 electrodes the voltage fields were detected across all frequencies. Since the substrate cannot conduct, those frequencies which appeared on any detector (sensor) were indicative of the conductive liquid pathways inside the substrate. An analysis algorithm was developed to visualize the fluid distributions under g-level conditions. Even though the duration of the experiment was short, gravity induced changes in fluid position were readily and reliably detected. Since fluids carry the nutrients necessary for plant growth these data and techniques can lead to the development of a uniform nutrient supply system supportive of optimal plant growth in space.

Algorithms↗
PubMed1993

Cardiac transplantation in New Jersey.

Heart transplantation is an effective treatment for end-stage congestive heart failure resulting in a one-year survival of 80 percent and a return to normal function in 90 percent of survivors. Refinements in the pre- and postoperative medical management of transplant recipients portend further benefits.

Actuarial Analysis↗
PubMed1992

Perinatal cocaine exposure and functional brainstem development in the rat.

Rat pups exposed to cocaine via maternal intromission throughout gestation and lactation displayed significantly prolonged auditory brainstem response component latencies and interwave intervals. Longitudinal analysis revealed that this effect was most pronounced on the 22nd postnatal day. Increasing the rate of stimulation further impaired neurosensory transmission in the caudal auditory pathway. These results indicate that both axonal and synaptic events may be affected to some degree and the timing (age) of optimum cocaine influence suggests that delayed myelination may be involved. The corresponding retardation in general development of the cocaine exposed pups further implicates maternal, fetal and postnatal utilization of nutritional resources as the basis for this outcome.

Analysis of Variance↗
PubMed1992

Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response.

Secretory IgA (sIgA) present at mucosal surfaces such as the lungs and intestine plays an important role in resistance to infection occurring at these anatomic sites. Because IL-2 and IL-4 can augment B cell proliferation and Ig production, we investigated possible adjuvant effects of these cytokines on bacterial polysaccharide-specific pulmonary sIgA generation. As shown in previous studies, intranasal immunization with liposomes containing bacterial polysaccharide from Aerobacter levanicum and Pseudomonas aeruginosa resulted in increased numbers of bacterial polysaccharide-specific pulmonary plasma cells and sIgA titers, compared with those found in unimmunized mice. Inclusion of IL-2, but not IL-4, into the intranasally administered liposomes further increased titers of bacterial polysaccharide specific sIgA and pulmonary plasma cells. Intranasal vaccination with liposomes containing bacterial polysaccharide and 10 micrograms/kg IL-2 increased bacterial polysaccharide-specific pulmonary plasma cell numbers by more than 80-fold compared with the response in mice immunized with liposomes containing bacterial polysaccharide, but without IL-2. The percentage of pulmonary plasma cells producing antibody to polysaccharide from A. levanicum rose from 0.14% in mice intranasally immunized with liposomes containing only polysaccharide to 4.1% in animals vaccinated with liposomes containing polysaccharide and IL-2. Intranasal immunization with liposomes containing P. aeruginosa polysaccharide and IL-2 significantly reduced mortality from P. aeruginosa pneumonia. These results demonstrate that IL-2 has potent adjuvant effects on bacterial Ag-specific sIgA production in the lungs when included in intranasally administered liposomes.

Adjuvants, Immunologic↗
PubMed1992

Proton uptake accompanies formation of the ternary complex of citrate synthase, oxaloacetate, and the transition-state analog inhibitor, carboxymethyl-CoA. Evidence that a neutral enol is the activated form of acetyl-CoA in the citrate synthase reaction.

Citrate synthase complexes with the transition-state analog inhibitor, carboxymethyl-CoA (CM-CoA), are believed to mimic those with the activated form of acetyl-CoA. The X-ray structure [Karpusas, M., Branchaud, B., & Remington, S.J. (1990) Biochemistry 29, 2213] of the ternary complex of the enzyme, oxaloacetate, and CMCoA has been used as the basis for a proposal that a neutral enol of acetyl-CoA is that activated form. Since the inhibitor carboxyl has a pKa of 3.90, analogy with an enolic acetyl-CoA intermediate leads to the prediction that a proton should be taken up from solution upon formation of the analog complex so that the transition-state analog carboxyl is protonated when bound. We have obtained evidence in solution for this proposal by comparing the isoelectric points and the pH dependence of the dissociation constants of the ternary complexes of the pig heart enzyme with the neutral ground-state analog inhibitor, acetonyl-CoA (KCoA), and the anionic transition-state analog inhibitor (CMCoA) and by studying the NMR spectra of the transition-state analog complexes of allosteric (Escherichia coli) and nonallosteric (pig heart) enzymes. The pH dependence of the dissociation constant of the ground-state analog indicates no proton uptake, while that for the transition-state analog indicates that 0.55 +/- 0.04 proton is taken up when the analog binds to the citrate synthase-oxaloacetate binary complex. The overall charges of ternary complexes of the pig heart enzyme with the transition-state and ground-state analog inhibitors are the same, as monitored by their isoelectric points.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗
PubMed1992

n-butyrate reduces the expression of beta-galactoside alpha 2,6-sialyltransferase in Hep G2 cells.

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.

Antigens, CD↗
PubMed1992

Late results of suprarenal Greenfield vena cava filter placement.

Placement of the Greenfield filter above the renal veins was necessary in 71 (9%) of 821 total patients in the filter registries of two institutions. The status of 60 patients (85%) could be verified, with follow-up data ranging from 18 months to 16 years (average, 53 months). Of 24 deaths (34%), none was from recurrent embolism or renal failure; death was most commonly associated with a malignant neoplasm. The recurrent embolism rate was 4%, identical to the infrarenal experience. Duplex evaluation of the filters in 22 patients, representing the majority (61%) of living patients, showed that all the filters were patent. Sixteen patients (41%) had lower-extremity edema that predated filter insertion, and in no patient did the results of noninvasive venous studies worsen. Filter fracture (two patients) or distal migration (two patients) had no clinical sequelae, and there was no evidence of renal dysfunction. For thrombus extending to the level of the renal veins or within them and for pregnant patients or women of childbearing age, suprarenal placement of the Greenfield filter is safe and effective, with no filter obstruction seen in follow-up extending to 16 years.

Adolescent↗
PubMed1992

Early evidence of beneficial effects of chordal preservation in mitral valve replacement on left ventricular dimensions.

Earlier authors have shown the improved left ventricular (LV) function after chordae-preserving mitral valve replacement (MVR) in follow-up studies. Seventy-nine consecutive patients undergoing MVR were studied preoperatively and pre-discharge with M-mode and two-dimensional Color Doppler echocardiography for early LV morphometric changes. Conventional MVR was performed in 42 patients (Group 1) and the posterior leaflet-chordae-papillary muscle complex was preserved in 37 patients (Group 2). Both cohorts were similar in age, sex, preoperative NYHA class and valve pathology. Four St. Jude bioprostheses, 9 Medtronic and 66 Sorin prostheses were implanted. The intraoperative and perioperative management protocol was uniform for both groups. The median left atrial dimension in both groups decreased to better physiological levels (53 to 46 mm in group 1, 52.5 to 46 mm in group 2). The median LV enddiastolic dimension increased from 47 to 48 mm in group 1 while it decreased from 56.5 to 49 min in group 2. The median LV endsystolic dimension remained unchanged in group 1 but decreased in group 2 (37.6 to 36 mm). Echocardiographic documentation of such early changes in the LV dimensions after modified MVR indicates that the beneficial effects of chordal preservation become evident early in the postoperative period and may explain the improved perioperative LV function after modified MVR compared to conventional MVR.

Adolescent↗
PubMed1992

In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria.

A study of the in-vitro activity of RP 59500, a semisynthetic derivative of pristinamycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococci (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect. The activity against MRSA, and against erythromycin-resistant strains of all species was particularly interesting.

Erythromycin↗
PubMed1992

The power of the N-test of haplotype concordance.

The N-test of haplotype concordance among siblings affected by some disease under investigation is used to decide whether there is a disease susceptibility gene linked to a marker locus or chromosomal region. The use of this test and appropriate modifications of it is briefly reviewed. The power of the ordinary N-test is then derived as a function of several parameters. The sample size needed to attain a given power is then derived. Some of the parameters are specified and the required sample sizes are given in tables for different values of the main unknown parameters.

Algorithms↗