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Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 145 records · Page 8Linked to original sources
PubMed1998

Echocardiographic detection of pulmonary valve papillary fibroelastoma.

Papillary fibroelastomas of the heart are rare lesions usually discovered at autopsy or incidentally at surgery. Although these lesions are benign and generally asymptomatic, they can cause valvular dysfunction or embolize to vital structures. In this case report, we describe a pulmonary valve papillary fibroelastoma detected by echocardiography in an adult. Most of the 12 cases of pulmonary valve papillary fibroelastoma reported in the literature were discovered incidentally at autopsy or during surgery. To our knowledge, this is the first reported case of pulmonary valve papillary fibroelastoma detected by echocardiography. Rest imaging before exercise echocardiography for evaluation of atypical chest pain in a 42-year-old white female demonstrated a mass on the pulmonary valve. The mass was further characterized by transesophageal echocardiography and excised during open heart surgery. Pulmonary valve papillary fibroelastoma was diagnosed histopathologically. This case illustrates the additional diagnostic value of comprehensive 2D imaging in the rest phase before doing exercise echocardiography.

Adult↗
PubMed1997

Differential induction of DNA-binding activities following CD19 cross-linking in human B lineage cells.

The B cell-specific cell surface molecule CD19 is expressed at all stages of B cell development, including normal plasma cells, and mediates signal transduction via interaction with cytoplasmic effector proteins. Cross-linking CD19 on early human B lineage cells induces the formation of a CD19/Vav/phosphatidylinositol-3 kinase complex, tyrosine phosphorylation of CD19 and Vav, and activation of the Ras pathway. To further explore the ramifications of CD19 signaling, the current study examined whether phosphorylation of Elk-1, activation of activator protein-1 (AP-1), or activation of nuclear factor-kappaB (NF-kappaB) transcription factors occurred following CD19 cross-linking. The cells used were the BLIN-1 pre-B cell line expressing low levels of cell surface mu heavy chain associated with surrogate light chain and the 1E8 immature B cell line expressing cell surface mu/kappa. Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fusion protein in vitro, whereas no phosphorylation of Elk-1 fusion protein occurred using lysates from CD19 cross-linked BLIN-1 cells. An electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus oligonucleotides was used to demonstrate that AP-1 -binding activity increased, while constitutive NF-kappaB-binding activity was not enhanced, following 2 h of CD19 cross-linking in 1E8 cells. Supershift experiments revealed that JunD and c-Fos proteins mediated anti-CD19 induced AP-1-binding activity in 1E8 cells. In contrast, CD19 cross-linking in BLIN-1 cells resulted in the induction of NF-kappaB, but had no apparent effect on AP-1-binding activity. These data suggest that CD19-mediated signal transduction activates different transcription factors at juxtaposed stages of B cell development that may culminate in the activation or suppression of distinct sets of genes.

Antigens, CD19↗
PubMed1997

Constitutional inversion of chromosome 7 and hematologic cancers.

Nonrandom aberrations of chromosome 7 have been described in various hematopoietic disorders. We describe here two unrelated families with the same constitutional inversion of chromosome 7 [inv(7)(q11.2q22)]. The probands in both families had acute leukemia and cytogenetic analysis revealed that the inversion was the sole cytogenetic abnormality in the bone marrow at diagnosis. There is a history of hematologic diseases in one of these families that included a son who is a carrier of this constitutional inversion. The distal inversion breakpoint lies within the common region of chromosome loss identified in some myeloid diseases. These observations raise the possibility that this inherited chromosome rearrangement could result in a mutation of a tumor suppressor gene and possibly represent a predisposing event for the development of leukemia in these individuals.

Aged↗
PubMed1997

Activating mutations in the N- and K-ras oncogenes differentially affect the growth properties of the IL-6-dependent myeloma cell line ANBL6.

Although the underlying genetic defect in multiple myeloma is unknown, activating mutations in the N- and K-ras oncogenes are common. Recent studies have suggested that ras mutations are associated with disease progression. We have introduced an activated N-ras12, N-ras61, or K-ras12 cDNA into the interleukin 6 (IL-6)-dependent multiple myeloma cell line ANBL6 to determine the effect of N- and K-ras on the growth/death properties of ANBL6. All three transduced cell populations demonstrate a growth advantage over the parent ANBL6 when propagated on normal human bone marrow stromal cells. In the absence of bone marrow stromal cells, augmentation of growth was observed in all three mutant ras-expressing populations at optimal and suboptimal concentrations of IL-6. Furthermore, in the absence of IL-6, all mutant ras populations demonstrated an augmentation in DNA synthesis when compared to the parent ANBL6. However, growth of the K-ras12 population in the absence of IL-6 was significantly inhibited when compared to the mutant N-ras populations. This could be explained by the observation that in the absence of IL-6, N-ras12 and N-ras61 suppress apoptosis, whereas K-ras12 does not. We also found that mutant ras expression could result in early protection from glucocorticoid-induced apoptosis similar to that observed by the addition of IL-6. However, the combination of mutant ras and IL-6 could completely block the glucocorticoid induction of apoptosis in long-term cultures. These data suggest that mutations in different ras family members may have similar or distinct effects on myeloma tumor growth and death and may alter the response to glucocorticoid treatment.

Apoptosis↗
PubMed1997

Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjögren syndrome.

Nonobese diabetic (NOD) mice develop an anti-exocrine gland pathology similar to human Sjögren syndrome. Recently, we demonstrated that NOD-scid mice develop severe loss of submandibular acinar cells with concomitant appearance of abnormal isoforms of salivary proteins suggesting de novo enzymatic cleavage. Because these changes may indicate activation of apoptotic proteases, we examined saliva and salivary tissue for cysteine protease activity. Cysteine protease activities were elevated in saliva and gland lysates from 20-week-old NOD and NOD-scid mice as compared with age- and sex-matched BALB/c or 8-week-old NOD mice. This activity appeared in the submandibular glands, but not in the parotid glands. Western blot analyses using antibodies directed against specific apoptotic proteases (interleukin 1beta converting enzyme, Nedd-2, and Apopain/CPP 32) confirmed these findings. Submandibular glands from NOD-scid mice exhibited the greatest increase in proteolytic activity, indicating that infiltrating leukocytes are not responsible for these changes. Western blot analyses also failed to reveal changes in the levels of cystatins (saliva proteins that inhibit protease activity). Thus, increased cysteine protease activity appears to be directly related to submandibular acinar cell loss in NOD-scid mice involving the apoptotic pathway. Additional protease activity in saliva and gland lysates of older NOD and NOD-scid mice, apparently mutually distinct from cysteine proteases, generated an enzymatically cleaved parotid secretory protein. We suggest, therefore, that proteolytic enzyme activity contributes to loss of exocrine gland tolerance by generating abnormally processed protein constituents.

Aging↗
PubMed1997

Antisocial personality disorder and aggression in recently abstinent cocaine dependent subjects.

To study the relationship between cocaine abstinence symptoms, personality, and aggression, we used the Point Subtraction Aggression Paradigm (PSAP) to measure aggression in 18 subjects admitted for the treatment of cocaine dependence. Eight subjects met criteria for antisocial personality disorder (ASPD). There was a significant correlation between presence of ASPD and frequency of aggressive responding by stepwise multiple regression. When presence of ASPD was factored out of the correlations, there was no significant relationship between aggressive responding and cocaine craving, withdrawal symptoms, amount of cocaine used, or length of time since use. These preliminary results suggest that in cocaine dependent individuals seeking treatment, current aggression is most dependent on the individual's previous aggressive behavior.

Adult↗
PubMed1997

Intradural drop metastases in oligodendrogliomas.

The case history is presented of a patient with primary intracerebral oligodendroglioma, who received multiple therapies for local recurrence. Four years following the initial diagnosis, the patient presented with spinal cord compression due to intradural metastases. The patterns of recurrence and metastases in oligodendroglioma are discussed.

Adult↗
PubMed1997

The FMR1 and FMR2 mutations are not common etiologies of academic difficulty among school-age children.

The prevalence of the fragile X mental retardation (FMR) 1 and FMR2 full mutations (fM) was examined among 1014 school-age children with academic difficulties but without mental retardation. Both Southern blot and polymerase chain reaction analyses for FMR1 and FMR2 were performed on samples obtained from these children. No fM genes were found, and one FMR1 premutation was identified. The distribution of allele sizes for both genes was comparable to those reported for other clinical and normal population samples. These results suggest that neither the FMR1 nor the FMR2 mutation is a common etiology of academic failure among school-age children without mental retardation and that the prevalence of the FMR1 premutation is no more frequent in children with academic failure than it is in the general population.

Alleles↗
PubMed1997

Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair.

The human immunodeficiency virus type 1 (HIV-1) vpr gene is an evolutionarily conserved gene among the primate lentiviruses HIV-1, HIV-2, and simian immunodeficiency viruses. One of the unique functions attributed to the vpr gene product is the arrest of cells in the G2 phase of the cell cycle. Here we demonstrate that Vpr interacts physically with HHR23A, one member of an evolutionarily conserved gene family involved in nucleotide excision repair. Interaction of Vpr with HHR23A was initially identified through a yeast two-hybrid screen and was confirmed by the demonstration of direct binding between bacterially expressed recombinant and transiently expressed or chemically synthesized protein products. Visualization of HHR23A and Vpr by indirect immunofluorescence and confocal microscopy indicates that the two proteins colocalize at or about the nuclear membrane. We also map the Vpr-binding domain in HHR23A to a C-terminal 45-amino-acid region of the protein previously shown to have homology to members of the ubiquitination pathway. Overexpression of HHR23A and a truncated derivative which includes the Vpr-binding domain results in a partial alleviation of the G2 arrest induced by Vpr, suggesting that the interaction between Vpr and HHR23A is critical for cell cycle arrest induced by Vpr. These results provide further support for the hypothesis that Vpr interferes with the normal function of a protein or proteins involved in the DNA repair process and, thus, in the transmission of signals that allow cells to transit from the G2 to the M phase of the cell cycle.

Amino Acid Sequence↗
PubMed1997

Radiographic evaluation of penetration by the femoral head into the polyethylene liner over time.

UNLABELLED: We examined the pattern of temporal penetration by thirty-two-millimeter-diameter femoral heads into polyethylene liners in a group of 105 hips (103 patients) in which an Arthropor metal-backed cup had been implanted. Each patient was evaluated radiographically and clinically at a minimum of four different postoperative intervals. The initial evaluation was performed a mean of 2.9 weeks (range, one to fifteen weeks) postoperatively, and the latest evaluation was performed a mean of 7.9 years (range, five to ten years) postoperatively. Two-dimensional wear - that is, penetration by the femoral head into the ultra-high molecular weight polyethylene liner - was determined from anteroposterior radiographs of the pelvis with a computer analysis system that calculated the change in the position of the center of the head relative to the center of the cup. Three new findings are reported. First, there was a large difference (mean, 1.1 millimeters) between the center of the head and that of the cup as measured on the initial postoperative radiographs. This difference underscores the need for researchers to consider the initial displacement of the head when measuring and reporting polyethylene wear. Second, although there was wide variation in responses among individuals, temporal examination of the data revealed a trend toward a decreasing rate of penetration with time. Moreover, the rate of penetration appeared to reach a steady-state value after the sixth postoperative year and remained nearly constant until the ninth postoperative year. Third, by comparing the subsets of patients who had the greatest and the least initial penetration by the head, we found that penetration behavior, although remarkably different between the groups in the first three years postoperatively, became similar with time. CLINICAL RELEVANCE: When making decisions regarding individual patients or hip systems that demonstrate penetration by the femoral head into the polyethylene liner, clinicians should consider the patterns of penetration over time. Measurements of the amount and rate of penetration that are based solely on the most recent radiograph do not represent the full clinical picture. We advocate more frequent radiographic follow-up and, when available, analysis of serial radiographs for patients who have excessive penetration by the femoral head into the acetabular liner.

Adult↗
PubMed1996

Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays.

Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.

Amino Acid Sequence↗
PubMed1996

Inhibition of nitric oxide synthesis does not improve interleukin-2-mediated antitumor effects in vivo.

Nitric oxide (NO) decreases cytotoxicity and proliferation of cytotoxic lymphocytes (CTLs) in vitro. Both can be prevented by inhibitors of the NO synthase (NOS). To elucidate whether inhibition of the IL-2-induced NOS could boost efficacy of IL-2-stimulated CTLs in vivo, we assessed lung metastases in mice injected with IL-2, the NOS inhibitor aminoguanidine (AG), their combination and the diluent. No improvement was observed for IL-2 + AG compared to IL-2 while NO production was normalized. Since NO causes one of the two major side effects of IL-2 treatment, hypotension, we further studied whether capillary leak could be attributed to NO, too. While IL-2-inducible NO was reduced to control levels by AG, pulmonary edema was unaffected. Thus a decrease in NO does not improve antitumor effects of IL-2-stimulated CTLs nor does it attenuate IL-2-associated capillary leak.

Animals↗
PubMed1996

The importance of thrombus organization and stellate cell phenotype in collagen I gene expression in human, coronary atherosclerotic and restenotic lesions.

OBJECTIVES: Collagen synthesis is one of the major mechanisms of primary atherosclerotic plaque growth and is likely to be similarly important in restenosis. The patterns of collagen gene expression in human restenosis and associations with thrombosis/hemorrhage have not been described. METHODS: Using human coronary artery samples obtained via the atherectomy catheter, we compared primary plaques (40 specimens) and restenotic lesions (41 specimens) for type I collagen gene expression using immunocytochemistry (SPI.D8 antibody to type I procollagen, an intracellular precursor of mature collagen) with subsequent computer image analysis. RESULTS: Scattered positive cells were identified in specific, non-random patterns. According to logistic regression analyses, type I procollagen gene expression seems to be more closely associated with certain morphological features (organized thrombus, microvessels, regions enriched with stellate cells) than with belonging to a primary vs. a restenotic sample. However, there may be a tendency for restenotic tissue to have slightly higher numbers of type I procollagen-positive cells than primary lesion tissue. CONCLUSIONS: Symptomatic primary and restenotic lesions exhibit similar patterns of type I collagen gene expression. Plaque microvessels and thrombi/hemorrhages (common features of both kinds of advanced lesions) might stimulate collagen synthesis equally well irrelevant to the nature of the lesion.

Adult↗