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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 73 records · Page 4Linked to original sources
PubMed2001

Circletail, a new mouse mutant with severe neural tube defects: chromosomal localization and interaction with the loop-tail mutation.

Circletail (Crc) is a new mouse mutant that exhibits a severe form of neural tube defect, craniorachischisis, in which almost the entire neural tube fails to close. This phenotype is seen in very few other mutants, the best characterized of which is loop-tail (Ltap(Lp), referred to hereafter as Lp). We tested the possibility of allelism between Lp and Crc by intercrossing Lp/+ and Crc/+mice. A proportion of double heterozygotes (Lp/+,Crc/+) exhibit craniorachischisis, revealing failure of complementation. However, genetic analysis shows that Crc is not linked to the markers that flank the Lp locus and cannot, therefore, be an allele of Lp. A genome-wide scan has localized the Crc gene to a region of 8.8 cM on central chromosome 15. Partial penetrance of the craniorachischisis phenotype in Crc/+,Lp/+double heterozygotes suggests the existence of a third, unlinked genetic locus that influences the interaction between Crc and Lp.

Alleles↗
PubMed2001

Hiv-associated nephropathy occurring before HIV antibody seroconversion.

It currently is thought that human immunodeficiency virus-associated nephropathy (HIVAN) occurs late in the course of HIV infection. Although HIVAN may be the presenting manifestation of acquired immunodeficiency syndrome (AIDS), it usually occurs after a prolonged period of viral infection often associated with high levels of HIV viremia. The patient described here developed HIVAN as a manifestation of acute retroviral syndrome. A 41-year-old black man presented with nephrotic range proteinuria, renal insufficiency, and acute gastrointestinal and pulmonary symptoms. He recently had been treated for primary syphilis. Two HIV serologic tests, performed 3 months apart, were negative. Renal biopsy was consistent with HIVAN. After the biopsy, the patient was discovered to have more than 700,000 viral copies per mL in his blood. CD4(+) count was greater than 500/mm(3). Six weeks later, enzyme-linked immunosorbent assay and Western blot analyses for HIV antibody became positive. HIVAN can occur early in the course of HIV infection, even during acute infection before seroconversion, and prolonged exposure to virus is not necessary for this renal involvement to occur in the susceptible host.

AIDS-Associated Nephropathy↗
PubMed2001

Stability after laser in situ keratomileusis in moderately and extremely myopic eyes.

OBJECTIVE: To evaluate the stability, mechanism, and degree of regression following laser in situ keratomileusis (LASIK) in cases with moderate to extreme myopia after 2 years of follow-up. SETTING: Single-center clinical trial. METHODS: Fifty-two eyes of 38 patients were enrolled in the study. One year follow-up was available for 47 eyes of 35 patients and 2 year follow-up for 39 eyes of 27 patients. Eyes were divided into 2 groups based on the level of preoperative myopia: Group 1, moderate to high myopia > or =15.0 diopters (D) (range -7.0 to -15.0 D, n = 24); Group 2, extreme myopia >15.0 D (range -15.3 to -25.8 D, n = 15). Laser in situ keratomileusis was performed using the Chiron Automated Corneal Shaper(R) microkeratome and the Summit OmniMed excimer laser. Manifest spherical equivalent, mean central keratometry, and central corneal thickness (CCT) were measured preoperatively and 12 and 24 months postoperatively. RESULTS: Group 1 exhibited a mild myopic shift (mean -0.07 +/- 0.28 D; P >.2) and a mild increase in keratometry (mean 0.05 +/- 0.46 D; P >.6), with an accompanying increase in CCT (mean 7.5 +/- 12.2 microm; (P =.006) at 24 months. Group 2 displayed a significant myopic shift (mean -0.7 +/- 0.7 D; P =.001) and a significant increase in keratometry (mean 0.4 +/- 0.5 D; P =.01), with a mild increase in CCT (mean 2.4 +/- 9.7 microm; P =.35) at 24 months. Corneal ectasia was evident in 1 eye in the extreme myopia group. CONCLUSION: The refractive effect of myopic LASIK up to -15.0 D remained reasonably stable during the second postoperative year. Significant regression of the refractive effect occurred in eyes with higher levels of myopia (>15.0 D), with the risk of progressive ectasia. Extreme caution is recommended when myopic LASIK is performed in eyes with higher levels of myopia.

Adult↗
PubMed2001

Identity and antibiotic susceptibility of enterobacterial flora of salad vegetables.

The enterobacterial flora from carrots (organic and non-organic) and salad vegetables has been identified and antibiotic susceptibilities determined. Pseudomonas fluorescens and Pantoea (formerly Enterobacter) agglomerans were the species most commonly found; the former was usually resistant to at least six of the antibiotics under test. Rahnella aquatilis (often producing beta-lactamase) was also found in carrots. There were no clear differences in flora from organic and non-organic carrots. Thus, uncooked vegetables are a potential source of highly resistant opportunistic pathogens.

Anti-Bacterial Agents↗
PubMed2001

Interactions between 23S rRNA and tRNA in the ribosomal E site.

Interactions between tRNA or its analogs and 23S rRNA in the large ribosomal subunit were analyzed by RNA footprinting and by modification-interference selection. In the E site, tRNA protected bases G2112, A2392, and C2394 of 23S rRNA. Truncated tRNA, lacking the anticodon stem-loop, protected A2392 and C2394, but not G2112, and tRNA derivatives with a shortened 3' end protected only G2112, but not A2392 or C2394. Modification interference revealed C2394 as the only accessible nucleotide in 23S rRNA whose modification interferes with binding of tRNA in the large ribosomal subunit E site. The results suggest a direct contact between A76 of tRNA A76 and C2394 of 23S rRNA. Protections at G2112 may reflect interaction of this 23S rRNA region with the tRNA central fold.

Anticodon↗
PubMed2001

Isolation and characterization of an unusual 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase gene from Enterobacter cloacae UW4.

A genomic library of the 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-containing plant growth-promoting bacterium Enterobacter cloacae UW4 in pUC19 in Escherichia coli was screened for the ability to utilize ACC as a sole source of nitrogen. One of the clones that was isolated contained a plasmid with an insert of approximately 0.8 kb that conferred ACC deaminase activity. Sequence analysis revealed that this DNA fragment contains an open-reading frame of 696 nucleotides predicted to encode a protein of 232 amino acids, a member of the amidohydrolase protein superfamily, i.e., a deaminase that contains a mononuclear or binuclear metal center as compared to the canonical ACC deaminase which contains pyridoxal phosphate as a co-factor.

Amino Acid Sequence↗
PubMed2001

The differential effect of injecting estradiol-17beta, testosterone, and hydrocortisone during the immune adaptive period on the fertility of female mice.

PROBLEM: Female mice injected with estradiol-17beta (E2) and testosterone during the immune adaptive period are infertile as adults. Study 1 examined the effect of the day of injection of E2 and testosterone on the incidence of infertility in two strains of mice. Study 2 examined the effect of hydrocortisone on E2-induced infertility. METHOD OF STUDY: Study 1: Neonatal (C57BL/6J x A/J)F1 B6A and (C3H/HeJ x 129J)F1 C31 female mice were injected from 0 to 3 and from 3 to 6 days of age with either 20 microg E2 or 20 microg testosterone. Animals were tested for fertility by mating with fertile males. Study 2: Neonatal B6A females were injected with 20 microg E2 with/without 1000 microg hydrocortisone on days 1, 3, 5, 7, and 10. At adulthood, ovaries were examined for the presence of corpora lutea (CLs). RESULTS: Study 1: The incidence of E2-induced infertility in adult B6A and C31 females decreased over three consecutive matings. In contrast, the incidence of testosterone-induced infertility in adult B6A and C31 females increased. E2 caused the highest incidence of infertility in C31 females when injected prior to 3 days of age. In B6A mice, E2 caused the highest incidence of infertility when injected after 3 days of age. Study 2: When hydrocortisone was injected with E2, 90% of the B6A females had ovaries with CLs at 100 days of age. Without hydrocortisone, only 16% of the B6A females injected with E2 had ovaries with CLs. CONCLUSION: Study 1: The incidence of infertility caused by injections of E2 is dependent on the strain of mice and the day(s) injected. The incidence of infertility caused by injections of testosterone is independent of the strain of mice. Study 2: Hydrocortisone prevents E2-induced infertility. It is proposed that injections of E2 during the immune adaptive period alter T-cell maturation, which contributes to E2-induced infertility.

Adaptation, Physiological↗
PubMed2001

Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells.

Chronic lymphocytic leukemia (CLL) is associated with impaired immunoglobulin (Ig) class-switching from IgM to IgG and IgA, a defect that leads to recurrent infections. When activated in the presence of leukemic CLL B cells, T cells rapidly up-regulate CD30 through an OX40 ligand and interleukin 4 (IL-4)-dependent mechanism. These leukemia-induced CD30+ T cells inhibit CD40 ligand (CD40L)-mediated S mu-->S gamma and S mu-->S alpha class-switch DNA recombination (CSR) by engaging CD30 ligand (CD30L), a molecule that interferes with the assembly of the CD40-tumor necrosis factor receptor-associated factor (TRAF) complex in nonmalignant IgD+ B cells. In addition, engagement of T cell CD30 by CD30L on neoplastic CLL B cells down-regulates the CD3-induced expression of CD40L. These findings indicate that, in CLL, abnormal CD30-CD30L interaction impairs IgG and IgA production by interfering with the CD40-mediated differentiation of nonmalignant B cells.

B-Lymphocytes↗
PubMed2001

IpaC from Shigella and SipC from Salmonella possess similar biochemical properties but are functionally distinct.

Invasion plasmid antigen C (IpaC) is secreted via the type III secretion system (TTSS) of Shigella flexneri and serves as an essential effector molecule for epithelial cell invasion. The only homologue of IpaC identified thus far is Salmonella invasion protein C (SipC/SspC), which is essential for enterocyte invasion by Salmonella typhimurium. To explore the biochemical and functional relatedness of IpaC and SipC, recombinant derivatives of both proteins were purified so that their in vitro biochemical properties could be compared. Both proteins were found to: (i) enhance the entry of wild-type S. flexneri and S. typhimurium into cultured cells; (ii) interact with phospholipid membranes; and (iii) oligomerize in solution; however, IpaC appeared to be more efficient in carrying out several of the biochemical properties examined. Overall, the data indicate that purified IpaC and SipC are biochemically similar, although not identical with respect to their in vitro activities. To extend these observations, complementation analyses were conducted using S. flexneri SF621 and S. typhimurium SB220, neither of which is capable of invading epithelial cells because of non-polar null mutations in ipaC and sipC respectively. Interestingly, both ipaC and sipC restored invasiveness to SB220 whereas only ipaC restored invasiveness to SF621, suggesting that SipC lacks an activity possessed by IpaC. This functional difference is not at the level of secretion because IpaC and SipC are both secreted by SF621 and it does not appear to be because of SipC dependency on this native chaperone as coexpression of sipC and sicA in SF621 still failed to restore detectable invasiveness. Taken together, the data suggest that IpaC and SipC differ in either their ability to be translocated into host cells or in their function as effectors of host cell invasion. Because IpaB shares significant sequence homology with the YopB translocator of Yersinia species, the ability for IpaC and SipC to associate with this protein was explored as a potential indicator of translocation function. Both proteins were found to bind to purified IpaB with an apparent dissociation constant in the nanomolar range, suggesting that they may differ with respect to effector function. Interestingly, whereas SB220 expressing sipC behaved like wild-type Salmonella, in that it remained within its membrane-bound vacuole following entry into host cells, SB220 expressing ipaC was found in the cytoplasm of host cells. This observation indicates that IpaC and SipC are responsible for a major difference in the invasion strategies of Shigella and Salmonella, that is, they escape into the host cell cytoplasm. The implications of the role of each protein's biochemistry relative to its in vivo function is discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Adverse metabolic and cardiovascular risk following treatment of acute lymphoblastic leukaemia in childhood; two case reports and a literature review.

We report two patients who survived childhood acute lymphoblastic leukaemia (ALL) following treatment with chemotherapy, total body irradiation (TBI) and bone marrow transplantation (BMT). The first case presented with an acute cerebral infarction at 23 years of age and was found to have non-ketotic diabetes and gross mixed hyperlipidaemia; the second presented with non-ketotic diabetes, hypertension, proteinuria and dyslipidaemia at age 16 years. The association of glucose intolerance with other vascular risk factors in young adult survivors of BMT was recently highlighted in a follow-up study of 23 survivors of BMT [1], but none presented with such gross mixed hyperlipidaemia. The improving survival rates of childhood malignancy over the last two decades will present adult physicians with patients who have accelerated vascular risk at a young age who will require early treatment to modify it.

Adolescent↗
PubMed2001

Role of iron in progressive renal disease.

The importance of iron in renal injury is derived from the ease with which iron is reversibly oxidized or reduced, enabling it to participate in the production of free radicals. Experimental evidence for the role of oxidants and iron in progressive renal disease falls into two broad categories. First, considerable data implicate oxidants in the proteinuria of glomerular disease. To the extent that proteinuria is an important determinant of progression, reduction of proteinuria would result in retardation of progression. Evidence also suggests a role of oxidants and iron in diabetic nephropathy, a major cause of end-stage kidney disease. Second, more direct studies have examined the role of oxidants and iron in models of progressive renal disease. These studies include the demonstration of increased iron in the kidney in models of progressive kidney disease; enhanced generation of oxidants, providing a mechanism by which iron can be mobilized; and more direct evidence of the beneficial effect of iron-deficient diets and iron chelators. Although the collective information on the role of oxidants and iron derived from in vitro studies and animal models of glomerular disease and progressive renal failure is impressive, control studies of patients are needed to show the efficacy of antioxidants and/or iron chelators in retarding the progression of renal failure and may offer an important therapeutic modality to patients with renal disease.

Animals↗
PubMed2001

Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.

Adult↗