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Biomedical subjects

S Sinha

Publications and source records attributed to S Sinha.

At least 343 records · Page 19Linked to original sources
PubMed1993

Serine phosphorylation of the secreted extracellular domain of APP.

The phosphorylation status of full-length APP (FL-APP) and secreted APP (s-APP) was investigated in stably transfected cells. 32P incorporation was detected in the mature full-length APP both in the absence and presence of phorbol ester. Surprisingly, 32P-phosphate was incorporated in the secreted ectodomain, and this was stable to treatment of the [32P]-phospho-s-APP with a large excess of PNGase F, suggesting that N-linked oligosaccharide sites do not account for phosphate incorporation. Phosphoamino acid analysis of the [32P]-phospho-s-APP resulted in the recovery of [32P]-phosphoserine as the preponderant species. Brefeldin A completely inhibited the release of [32P]-phospho s-APP, but did not inhibit the incorporation of 32P into the FL-APP, suggesting that phosphorylation occurs early in the central vacuolar pathway. It is possible that ectodomain phosphorylation by a novel luminal or extracellular protein kinase may play a role in regulating the metabolic fate of APP.

Amino Acids↗
PubMed1993

Adenosine diphosphate stimulation of cultured hematopoietic cell lines.

Adenosine diphosphate (ADP) plays a critical role in platelet activation both by exogenous stimulation and the release of endogenous intracellular stores. As the platelet ADP receptor is not well defined, we have chosen to identify and characterize several cell lines that possess functional receptors for this nucleotide. Rat promegakaryoblasts (RPM), human erythroleukemia cells (HEL), U937, and K562 leukemia cells responded to ADP, as measured by a rapid increase in intracellular calcium. In the case of RPM cells, ADP was the only naturally occurring platelet agonist capable of eliciting this response. Binding studies with [3H]ADP and fixed cells showed 3.99 +/- 1.77 x 10(5) binding sites/cell for RPM cells (apparent dissociation constant [kd] = 7.75 +/- 2.3 x 10(-8) mol/L), 8.19 +/- 3.25 x 10(5) sites/cell for HEL cells (kd = 2.15 +/- 0.84 x 10(-7) mol/L, 1.15 +/- 0.23 x 10(6) sites/cell for U937 cells (kd = 2.20 +/- 0.53 x 10(-7) mol/L) and 5.39 +/- 2.80 x 10(5) sites/cell for K562 cells (kd = 1.37 +/- 0.39 x 10(-7) mol/L), Inhibition studies with unlabeled nucleotides and analogues showed that binding was approximately 85% specific and the inhibitory pattern was similar to that seen with mature platelets. The purine base adenosine resulted in little or no inhibition. These studies indicate that both human and rat hematopoietic cell lines possess intact ADP receptors and may be useful tools in future studies of the structure and function of this important platelet-activation system.

Adenosine Diphosphate↗
PubMed1993

Regulated cleavage of Alzheimer beta-amyloid precursor protein in the absence of the cytoplasmic tail.

Alzheimer beta-amyloid precursor protein can be phosphorylated on residues Thr654, Ser655 and Thr668 on its cytoplasmic domain. Proteolytic cleavage of the amyloid precursor protein and release of the amyloid precursor protein ectodomain into the medium of cultured cells can be activated by phorbol esters which stimulate protein kinase C. In the present study, using mutated amyloid precursor protein, we show that phosphorylation of cytoplasmic residues is not required for the phorbol ester-activated cleavage and release of the amyloid precursor protein ectodomain. Remarkably, deletion of the entire amyloid precursor protein cytoplasmic tail had no effect on the phorbol ester-activated cleavage/release. The results indicate that activation of amyloid precursor protein cleavage/release by protein kinase C involves phosphorylation of some component of the processing pathway, instead of or in addition to the cytoplasmic tail of the amyloid precursor protein.

Amino Acid Sequence↗
PubMed1993

Cells with a familial Alzheimer's disease mutation produce authentic beta-peptide.

Cells overexpressing the beta-amyloid precursor protein possessing a mutation found in familial Alzheimer's disease overproduce beta-amyloid peptide (A beta). Because these findings were based on immunological identification, we have chemically characterized the peptides produced. Purified A beta fragments from the conditioned media of these cells were found to have N-terminal sequence consistent with the A beta found in cerebral plaques. Mass spectrometric data demonstrated a series of A beta fragments consistent with those found in Alzheimer's disease (AD); the major species corresponding to A beta(1-40). Significantly, a longer fragment corresponding to A beta(1-42) was found. These findings suggest that this cellular system may be useful for mechanistic studies of A beta generation and possibly for the development of therapeutic agents to treat AD.

Alzheimer Disease↗
PubMed1993

Definitive diagnosis of breast implant rupture using magnetic resonance imaging.

Breast implant rupture is an important complication of augmented and reconstructed breasts. Although several techniques such as mammography, xeromammography, ultrasound, thermography, and computed tomographic (CT) scanning have been proven to be useful to detect implant rupture, they have several disadvantages and lack specificity. In the current study, we have established magnetic resonance imaging (MRI) as a definitive, reliable, and reproducible technique to diagnose both intracapsular and extracapsular ruptures. The study was conducted in 100 symptomatic patients. Our imaging parameters were able to identify ruptures in implants with silicone shells. All the ruptures showed the presence of wavy lines, free-floating silicone shell within the gel ("free-floating loose-thread sign" or "linguine sign"). We had a 3.75 percent incidence of false-positive and false-negative results. The sensitivity for detection of silicone implant rupture was 76 percent, with a specificity of 97 percent. In addition, we also were able to identify the artifacts that may interfere with the definitive diagnosis of implant rupture.

Adult↗
PubMed1993

MR imaging of silicone breast implants: comparison of different coil arrays.

To determine the optimal coil and patient position for magnetic resonance imaging of patients with silicone breast implants, images obtained with body, circular surface, flexible, single shoulder, and dual shoulder coils in various numbers of patients were compared with regard to signal-to-noise ratio (S/N), decay of signal intensity, resolution, and key area coverage. Images obtained with the dual shoulder coil and prone position, with a customized positioning device, gave the best S/N, resolution, and coverage of the breasts and axillae.

Breast↗
PubMed1993

Methyl xanthine and altered biomembrane dynamics: demonstration of protein mobility and enzyme inhibition by caffeine in sperm model system.

Treatment of spermatozoa with 10 mM caffeine increases the rotational mobility of thiol-containing proteins in a defined micellar micro-environment. This is associated with inhibition of superoxide dismutase activity and augmented superoxide anion radical generation. Increased sperm competence in presence of caffeine in human oligospermia is explained by these observations. Inhibition of cyclic phosphodiesterase by caffeine is suggested to be part of the observed lattice-rearrangement.

Caffeine↗