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M Sy

Publications and source records attributed to M Sy.

15 recordsLinked to original sources
PubMed2000

The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome.

Familial prion diseases are thought to result from a change in structure of the mutant prion protein (PrP), which takes a pathogenic conformation. We have examined the role of molecular chaperones in the folding of normal and mutant PrP Q217R (PrP(217)) in transfected neuroblastoma cells. In a previous report we showed that, although most of the PrP(217) forms escape the endoplasmic reticulum quality control system and aggregate in post-Golgi compartments, a significant proportion of PrP(217) retains the C-terminal glycosylphosphatidyl inositol signal peptide (PrP32), and does not exit the endoplasmic reticulum (Singh, N., Zanusso, G., Chen, S. G., Fujioka, H., Richardson, S., Gambetti, P., and Petersen, R. B. (1997) J. Biol. Chem. 272, 28461-28470). We have now studied the folding and turnover of PrP32 to understand the mechanism by which abnormal PrP forms cause cellular toxicity in our cell culture model and in the human brain carrying the Gerstmann-Sträussler-Scheinker disease Q217R mutation. In this report, we show that PrP32 remains associated with the chaperone BiP for an abnormally prolonged period of time and is degraded by the proteasomal pathway. This study is the first demonstration that BiP is chaperoning the folding of PrP and plays a role in maintaining the quality control in the PrP maturation pathway. Our data provide new insight into the diverse pathways of mutant PrP metabolism and neurotoxicity.

Amino Acid Substitution↗
PubMed1999

Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis.

Proteins involved in class I MHC (MHC-I) Ag processing, such as the TAP, are deficient in some human tumor cells. This suggests that antitumor responses by CD8 T cells provide selection pressure to favor outgrowth of cells with defective processing of tumor Ags. Nonetheless, this evidence is only correlative, and controlled in vivo experiments have been lacking to demonstrate that TAP deficiency promotes survival of tumor cells. To explore the role of Ag processing defects in tumor progression, matched panels of TAP1-positive and TAP1-negative tumor cell lines were generated from a parental transformed murine fibroblast line. Inoculation of C57BL/6 mice with TAP1-negative cells produced large and persistent tumors. In contrast, TAP1-positive cells did not generate lasting tumors, although small tumors were detected transiently and regressed spontaneously. Both TAP1-positive and TAP1-negative cells produced tumors in athymic mice, confirming that TAP-dependent differences in tumorigenicity were due to T cell-dependent immune responses. Inoculation of C57BL/6 mice with mixtures of TAP1-positive and TAP1-negative cells produced tumors composed exclusively of TAP1-negative cells, indicating in vivo selection for cells with TAP deficiency. Thus, loss of TAP function allows some tumor cells to avoid T cell-dependent elimination, resulting in selection for tumor cells with deficient Ag processing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Dual phase helical CT of a primary malignant fibrous histiocytoma of the right renal vein.

A case is reported of primary malignant fibrous histiocytoma of the right renal vein involving the ipsilateral kidney which showed early enhancement on dual phase helical CT. The correct diagnosis of a primary tumour of the renal vein involving the kidney was not made but in retrospect could have been achieved pre-operatively by considering several CT features.

Histiocytoma, Benign Fibrous↗
PubMed1998

Contribution of computed tomography to decision making in the management of adhesive small bowel obstruction.

BACKGROUND: In adhesive small bowel obstruction, the early recognition of complications such as strangulation or volvulus is essential to choose between surgical or conservative initial treatment. The objective of this study was to determine prospectively the contribution of computed tomography (CT) to decision making in the management of these patients. METHODS: Patients with suspected adhesive small bowel obstruction had CT at admission. Patients with CT signs of volvulus or strangulation and/or clinical signs of peritoneal irritation underwent urgent surgery; other patients had conservative initial treatment. RESULTS: Fifty-four patients were evaluated. CT demonstrated signs of strangulation or volvulus in 19 patients, including three with signs of peritoneal irritation. Within this group, urgent laparotomy was performed in 17 patients and confirmed the CT diagnosis in 16. Thirty-seven patients without clinical or CT signs of complications had initial conservative treatment; among them, seven of 12 with a distal obstruction determined by CT required a delayed operation for persisting obstruction, compared with two of 25 patients with a proximal obstruction (P < 0.01). CONCLUSION: CT is useful for the evaluation of adhesive small bowel obstruction, to detect accurately patients with complications who require urgent operation and to determine the location of the adhesion, which represents a significant prognostic factor for success of conservative treatment.

Adult↗
PubMed1996

Pulmonary emphysema: quantitative CT during expiration.

PURPOSE: To determine whether measurement of the relative area of lung with attenuation coefficients lower than a certain threshold on thin-section computed tomographic (CT) scans obtained during expiration is a valuable method of quantifying the extent of pulmonary emphysema. MATERIALS AND METHODS: Eighty-nine patients underwent CT (with 1-mm collimation) preoperatively during inspiration and expiration. Relative areas of lung with attenuation coefficients lower than various thresholds were calculated. These relative areas were compared with areas found macroscopically to have emphysema (59 patients [51 men, eight women; aged 40-77 years]) and with two microscopic indices (35 patients [29 men, six women; aged 42-77 years]) assessed on the resected specimens. RESULTS: The valid expiratory CT thresholds were found to be -820 and 910 HU for microscopic and macroscopic emphysema, respectively. However, results of stepwise multiple regression analyses showed that the inspiratory threshold of -950 HU was superior for both macroscopically and microscopically quantified emphysema. The correlation coefficients in expiratory CT were higher for the pulmonary volumes but similar for the diffusing capacity. CONCLUSION: Expiratory quantitative CT is not as accurate as inspiratory CT for quantifying pulmonary emphysema and probably reflects air trapping more than reduction in the alveolar wall surface.

Adult↗
PubMed1996

Case report: Renal pseudotumours mimicking tumour recurrence after partial nephrectomy.

Partial nephrectomy and tumour enucleation are increasingly accepted as an organ sparing approach for small renal cell carcinomas. Repeated computed tomography or sonography for the early detection of tumour recurrence are mandatory during the follow-up. We report two cases of renal pseudotumour mimicking a tumour recurrence: one case is related to the pseudotumoral appearance on sonography of a tumour defect filled by a fatty flap, and the other to the relative migration of an accessory spleen into the site of the cuneiform nephrectomy. The recognition of renal pseudotumours following partial nephrectomy prevents confusion with tumour recurrence on follow-up examinations.

Adult↗
PubMed1995

[Clinical role of spiral tomodensitometry in pulmonary disorders].

Spiral CT of the lungs has taken the place of conventional CT in most indications. Until now, some specific indications, concerning the detection of lung nodules, the detection of central pulmonary thromboembolism and the description of the angioarchitecture of pulmonary arteriovenous malformations have been reported. This paper provides an overview of the clinical utility of this new technique.

Angiography↗
PubMed1994

Putative preneoplastic foci in the human prostate.

Our knowledge of prostate cancer is less well-defined than our knowledge of cancers of other organs. In the colon, for example, morphological criteria to identify carcinomas in situ and some putative preneoplastic lesions are clear; phenotypic differences in the expression of enzymes and antigens are documented in experimental models and are starting to be defined in humans. Experimental models of cancer of the liver and colon show evidence that "enzyme-altered foci" are preneoplastic. In these organs, the "normal" context is much clearer than in the prostate. In contrast, in the prostates of men in the same age range as those who develop prostate cancer, morphological aberrations are almost always present, diverse, and poorly understood. Murphy and Gaeta said that, "in the study of prostatic disease..., almost every aspect remains controversial...[and].... many of the 'known facts' concerning prostatic disease are poorly documented..." While being aware that the definitions of all benign and malignant lesions of the prostate are based on complex morphological criteria which must form the contemporary context for comparisons, our laboratory is searching for markers that will permit the identification of putative preneoplastic lesions in the prostate. In our opinion, these changes will not be found most efficiently, if they are present at all, in long established cell lines, advanced carcinomas, or serially transplantable xenografts of primary prostatic carcinomas. Our preliminary data suggest that several enzyme histochemical and immunohistochemical approaches are worthy of study. Markers that show promise include acid phosphatase, 5'-nucleotidase, leucine aminopeptidase, and CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1983

[Hemodynamic studies at rest and under stress in patients with coronary heart disease after administration of carteolol].

In 17 patients with coronary heart disease the influence of the beta-blocking agent 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone-hydrochloride) (carteolol hydrochloride, Endak, Endak mite) (0.4 mg i.v.) on heart rate, blood pressure, cardiac index, stroke volume index and pulmonary artery pressure at rest and during exercise was investigated. During exercise heart rate and cardiac index decrease significantly (p less than 0.005 and p less than 0.05, respectively). The differences in the stroke volume indices are not significant. The relationship between stroke volume index and mean pressure in the pulmonary artery shows a slight decrease after administration of carteolol at rest and a small increase of the mean pressure in the pulmonary artery during exercise. In patients with coronary heart disease left ventricular function does not change significantly at rest and during exercise after administration of carteolol.

Adult↗
PubMed1976

[Peculiarities of acute appendicitis in women].

A complete documentation of the clinical and operative findings and a comparison of these with the histologic diagnosis in nearly 900 appendectomy patients from a period of more than two years is presented. In this publication an account of the specific results of nearly 500 women is given. The influences of age, menstruation, and gynecologic illnesses are reported in detail. Sixty-five percent of all women were treated unnecessarily with appendectomy. However, the indications for this operation should not be limited on these grounds.

Acute Disease↗