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A Sobel

Publications and source records attributed to A Sobel.

At least 109 records · Page 6Linked to original sources
PubMed1989

Stathmin is a major phosphoprotein and cyclic AMP-dependent protein kinase substrate in mouse brain neurons but not in astrocytes in culture: regulation during ontogenesis.

Stathmin is a ubiquitous soluble protein (Mr approximately 19,000; pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. It is present in various tissues and cell types and has several nonphosphorylated and increasingly phosphorylated forms, and it is particularly abundant in brain. Very high concentrations of stathmin were also detected in mouse embryo striatal neurons grown in primary culture, whereas stathmin was barely detectable in astrocytes from the same source. Stathmin appeared in neurons as a major substrate for protein phosphorylation and, in particular, for the cyclic AMP (cAMP)-dependent protein kinase, because its phosphorylation was stimulated by cAMP in cell-free preparations and in intact cells by forskolin, a potent activator of adenylate cyclase. During brain ontogenesis, stathmin was first detected at embryonic day 12; its concentration increased until birth and then decreased from postnatal day 10 to adulthood. In parallel, its molecular forms shifted from the least phosphorylated to the more phosphorylated ones. This result may reflect the evolution of the activity of stathmin during development and the subsequent maturation of the brain. In conclusion, our results substantiate the likely role of stathmin as an intracellular relay of extracellular regulations, as they point out its specific importance related to neuronal functions and brain differentiation.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Phosphorylation of a group of proteins related to the physiological, multihormonal regulations of the various cell types in the anterior pituitary gland.

We previously identified a group of cytoplasmic phosphoproteins whose phosphorylation could be related to the multihormonal regulation of PRL in the homogeneous tumor-derived GH cell lines (set of proteins 1-11) and in heterogeneous normal anterior pituitary cells in culture (set of proteins 1-15). In normal cells, a mixture of hypothalamic hormones induced, like the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, stronger phosphorylation changes than TRH alone. Proteins of the set 1-15 are therefore likely to be present also in the nonmammotrophic anterior pituitary cell types, where their phosphorylation can be regulated by the hormones specific of the cell type considered. This interpretation is confirmed by the presence of the same proteins in cells of the corticotroph-like AtT-20/D16 cell line and the regulation of their phosphorylation by CRF. The same phosphoproteins were also detected in non dissociated anterior pituitary tissue from ovariectomized rats. Their phosphorylation was regulated by various hormones and other extracellular agents in a way similar to their regulation in anterior pituitary cells in culture. A 5-day estradiol implant pretreatment of the ovariectomized rats, which stimulates the anterior pituitary gland both directly and indirectly, resulted in a very high level of basal phosphorylation of proteins 1-15. Only very little further stimulation was achieved by the addition of exogenous hypothalamic hormones, indicating that the actual physiological regulatory pathways are the same as those unraveled in the various cell culture model systems. In conclusion, phosphorylation of proteins 1-15 1) can be related to the multihormonal regulation of the various anterior pituitary cell types in culture and 2) corresponds to intracellular molecular mechanisms actually involved in the physiological regulations of pituitary functions in the intact anterior pituitary gland.

Animals↗
PubMed1989

[Early relaparotomy in postoperative peritonitis].

The most frequent reason for relaparotomy is peritonitis, followed by mechanical ileus and secondary hemorrhage. The most common cause of postoperative peritonitis is insufficient anastomosis. The relative proportion of cases of localized peritonitis is increasing. Diffuse peritonitis is still treated by operation, according to instructions of Kirschner 1926, whereas localized peritonitis is more and more treated by percutaneous puncture. The prognosis of postoperative peritonitis is poor.

Aged↗
PubMed1989

[AIDS in 1989].

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Complications of plasma exchange in the treatment of polyarteritis nodosa and Churg-Strauss angiitis and the contribution of adjuvant immunosuppressive therapy: a randomized trial in 72 patients.

We recorded side effects and other complications of 813 plasma exchanges used in early treatment of polyarteritis nodosa and Churg-Strauss angiitis in a prospective study of 72 patients (22-75 years old). All the patients were also treated with a corticosteroid (1 mg/kg/day), and half were included in a randomized trial of cyclophosphamide (2 mg/kg/day during 1 year). Centrifugation was used in 678 plasma exchange sessions (83.4%) and filtration in 128 (15.7%) (no data were available about the technique used in seven cases). The replacement fluid in 745 sessions was 4% albumin and in 115 was fresh-frozen plasma; eight patients received both (47 sessions). Two hundred and fifty-one complications were reported in 60 patients during 206 (25.3%) of the 813 completed exchanges; 47 sessions (5.8%) were temporarily stopped as a result of complications. The most common problems were technical difficulties (in 90 sessions), moderate or severe hypotension (in 52), and allergy to the replacement fluid (in 51). Hepatitis B antigen appeared in one patient. In four patients, plasma exchange was stopped permanently because of the severe side effects. No patient died during a session. Twelve of the 72 patients died during the study, six in each of the two groups. In the group treated by a combination of corticosteroid and plasma exchange, deaths were related to the deleterious effects of the disease itself and occurred after 12.8 +/- 11.1 months (1-26 months). In the group treated by the same combination plus cyclophosphamide, four of the six deaths were due to severe infections, which were related to leukopenia in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Phosphorylation of intracellular proteins related to the multihormonal regulation of prolactin: comparison of normal anterior pituitary cells in culture with the tumor-derived GH cell lines.

We have previously identified a group of cytoplasmic phosphoproteins (proteins 1-11) whose phosphorylation could be related, on a pharmacological basis, to the multihormonal regulation of PRL synthesis and release in the anterior pituitary tumor-derived GH cell lines. Phosphoproteins with identical migration properties on two-dimensional electrophoresis gels were also detectable in normal rat anterior pituitary cells in culture. We designed appropriate culture and [32P] phosphate-labeling conditions allowing to analyze the regulation of the phosphorylation of these proteins in normal pituitary cells. TRH, 12-O-tetradecanoylphorbol-13-acetate, and vasoactive intestinal peptide induced the same qualitative changes in phosphorylation of proteins 1-11 in normal as in GH cells. Quantitative differences observed are most likely due to the heterogeneity of primary pituitary cultures. Phosphorylation changes affecting proteins 14-16, not previously detected in GH cells, were also observed with normal anterior pituitary cells. GH cell lines have lost the sensitivity of pituitary lactotrophs for dopamine, an important physiological inhibitor of PRL synthesis and release. In normal anterior pituitary cells in culture, dopamine inhibited also the TRH-stimulated phosphorylation of proteins 1-10, thus strengthening the correlation between phosphorylation of these proteins and multihormonal regulation of pituitary cell functions. Our results indicate: 1) that the same phosphoproteins as in GH cells are related to the multihormonal regulation of nontumoral, normal anterior pituitary cells in culture; 2) that dopamine acts by interfering with the phosphorylation of these proteins. The phosphoproteins described here are therefore likely to be part, in normal anterior pituitary cells and possibly in other cell types, of the intracellular machinery involved in the cascade of transducing events leading from the binding of extracellular signals to the regulation of their target biological functions.

Animals↗
PubMed1988

[Prognosis and treatment of glomerulonephritis of periarteritis nodosa. The role of plasma exchange].

Fourteen patients with polyarteritis nodosa complicated by histologically confirmed glomerulopathies were included in a prospective multi-center study comparing corticotherapy (group 1, n = 8) with combined cyclophosphamide and steroids (group 2, n = 6). Plasma exchanges were associated on a routine basis. The two groups were comparable apart from initially more severe renal impairment in group 1 (p less than 0.05). Initial control of the disease was obtained in 11 patients (7 from group 1, 4 from group 2) including the patients with oligoanuria. Six patients recovered, 3 had recurrence requiring chronic hemodialysis and 5 patients died from group 1 (p less than 0.05). These preliminary findings suggest that plasma exchange can contribute to control of polyarteritis nodosa with renal complications.

Adrenal Cortex Hormones↗
PubMed1988

[Treatment of AL amyloidosis without myeloma].

AL amyloidosis is a serious complication of monoclonal gammopathy. The therapeutic strategy in amyloidosis associated with myeloma is to decrease the amyloidogenic precursor synthetised by the monoclonal plasmocytic proliferation. However, when systemic amyloidosis complicates a so called "benign" monoclonal gammopathy, this therapeutic approach is debatable. We report 10 cases of AL amyloidosis without myeloma treated by chemotherapy. Eight patients were initially given alkylating agents (cyclophosphamide or melphalan) which had no effect on the clinical progression of their systemic amyloidosis or on the plasma concentrations of the precursor. A limited open clinical trial including 4 patients was then undertaken based on the Vincristine, Adriamycine, Dexamethasone combination recently proposed for cases of resistant myeloma. A 50% reduction in the serum monoclonal protein was observed in 2 patients with this treatment. However, the mean survival of the 10 patients (25 months) was not longer than that previously reported for patients receiving more conventional treatment. The results of this limited trial indicate the need for further controlled therapeutic trials with larger numbers of patients in order to assess the effect of polychemotherapy in patients with AL amyloidosis.

Adult↗
PubMed1988

[The cost of care related to AIDS at the Henri Mondor Hospital].

A retrospective analysis of the cost of hospital care related to AIDS was undertaken at Henri Mondor hospital, Créteil, to prepare the hospital budget for 1988. Eight representative cases of the type of medical care were thoroughly evaluated with inventories of all direct expenses (medico-technical, pharmaceutical, accommodation) incurred between the first hospital admission of each patient and June 1987 or the patient's death. The study comprises 17 hospital stays of over 24 hours or 439 days of diagnosis and treatment. The total daily direct expenditure varied from 979 to 1119 FF/day (depending on whether the drug Zidovudine was used), that is to say an increase of 7 to 23% compared with the previous average daily cost in the same hospital unit (909 FF/day). The density of personnel is lower than recommended for units receiving patients with advanced AIDS. This lack of personnel is responsible for an underevaluation of total cost of about 10%. Should the number of admissions with this disease increase, the hospital personnel budget would suffer the most, even if hospital admission for AIDS continues to substitute for other decreased or abandoned activities and do not therefore appear in total overexpenditure.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Plasma exchange in polyradiculoneuritis in AIDS].

Plasma exchange was used in three cases of peripheral neuropathy of polyradiculoneuritis type in patients with AIDS. The neurologic lesion in the first case was due to a cytomegalovirus, and plasma exchange appeared to provide additional benefits (to antiviral treatment) during the first attack of polyradiculoneuritis. The peripheral neurologic disorders were probably related to the HIV itself in the other two cases, and plasma exchange was carried out only briefly because of the seriousness of the situation, which was unaffected. Although plasma exchange is possible, if particular technical precautions are taken, in patients with AIDS, the present series is too small for valid scientific evaluation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Altered C1 inhibitor genes in type I hereditary angioedema.

Hereditary angioedema is an inherited disease transmitted as an autosomal dominant trait and characterized by deficient activity of C1 inhibitor, a glycoprotein that limits intravascular activation of complement. The unavailability of markers for the C1 inhibitor locus has so far precluded access to the genetic bases of the disorder. Using a recombinant-DNA probe for the C1 inhibitor gene, we identified a cluster of four distinctive DNA restriction sites in a multigeneration family. The strict cosegregation of these markers with a low C1 inhibitor level supports the conclusion that a defective structural gene is responsible for the disease. The occurrence of distinct DNA markers in patients from unrelated kinships indicates that, like forms of the condition displaying dysfunctional C1 inhibitor variants, those characterized by protein deficiency are also genetically heterogeneous. Although multiple restriction-site changes in the C1 inhibitor gene are carried by certain patients, DNA markers for this locus are strikingly infrequent among normal persons. These findings indicate that the gene alterations responsible for hereditary angioedema arise more often from DNA rearrangements than from nucleotide substitutions. Such variations in the structure of the C1 inhibitor gene may provide the basis for early and direct identification of persons at risk.

Angioedema↗
PubMed1987

[Hereditary angioneurotic edema. Treatment of a pseudosurgical digestive attack with C1 inhibitor concentrate].

Although anabolic androgens can be used to prevent acute attacks of hereditary angioneurotic oedema, these are still observed. When they are severe, and even more so when they involve the larynx or the abdominal viscera, an emergency treatment is necessary, ideally with the purified C1-inhibitor (C1-INH) administered by intravenous infusion. In a case with pseudo-surgical abdominal symptoms, this treatment was followed by an unusually dramatic regression of all symptoms. Serial laboratory examinations showed an increase in C1-INH and C2 plasma levels and in the number of basophils within less than 30 minutes; the increase in C4 levels occurred later. Thus, C1-INH is very effective in the treatment of acute hereditary angioneurotic oedema, but the product is not widely available; it should be reserved to severe forms affecting the larynx and the viscera.

Abdomen, Acute↗
PubMed1987

Protein phosphorylation in response to the tumor promoter TPA is dependent on the state of differentiation of muscle cells.

We have shown previously (A. Sobel and A. H. Tashjian, Jr. (1983). J. Biol. Chem. 258, 10,312-10,324;A. Sobel and M.C. Boutterin (1985). Neurochem. Int. 7, 995-1006) that, in the pituitary-derived GH4C1 cells, thyrotropin-releasing hormone or the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) stimulates the phosphorylation of two sets of cytoplasmic proteins related to the regulation of prolactin synthesis and release, respectively. Interestingly, phosphoproteins with identical electrophoretic migration properties on two-dimensional gels were detected in cultured neonate or adult mouse muscle cells and in the L6 and C2 myogenic cell lines. In addition TPA, which is known to have many actions on muscle cell functions, proliferation, and differentiation, stimulated the phosphorylation of these same proteins in myoblasts in culture. After fusion of the proliferating myoblasts into differentiated myotubes, this TPA-induced stimulation was strongly reduced in normal muscle cell cultures where some mononucleate muscle and non-muscle cells remained present. It was totally abolished in the homogeneous L6 and C2 cell lines. These observations suggest that the same phosphoproteins may be related to the intracellular mechanisms involved in the transduction of extracellular regulatory signals in such distinct differentiated environments as those of pituitary and muscle cells. In muscle cells themselves, the regulation of the phosphorylation of these proteins is function of the cell's state of differentiation.

Animals↗
PubMed1987

Relapses of idiopathic diffuse crescentic glomerulonephritis without immune deposits: report of 6 cases.

Idiopathic diffuse crescentic glomerulonephritis without immune deposits is a variant of rapidly progressive glomerulonephritis which can account for up to 40% of crescentic nephritis. The prognosis may depend on both the severity of histological injury at presentation and the efficacy of treatment. Recent advances in therapy have improved the outlook further, and prolonged stable remissions with mild renal failure can occur which contrast with the previously common evolution towards end-stage renal failure within a few weeks. However, relapses in otherwise stable remission may be seen, and we describe a series of 6 acute relapses interrupting such prolonged remissions. The relapses were defined by clinical and histological means. This modification of the natural history of some crescentic glomerulonephritis may reflect new therapeutic strategies, and the relapses may reflect a cyclical nature to the disease evolution which was previously hidden by hemodialysis. The possibility of successive flares suggests that kidney biopsies should be repeated when a rapid deterioration of renal function occurs, since treatment such as high-dose steroids and/or plasma exchange can be again effective if started early.

Adult↗
PubMed1987

[Circulating anticoagulant of the antiprothrombinase type. Retrospective study of 134 cases].

A retrospective study of 134 cases of circulating "lupus anticoagulant" (LA) observed between 1975 and 1985 in the haemostasis laboratory of Henri Mondor Hospital is reported. In 66 p. 100 of cases the circulating anticoagulant was discovered fortuitously and auto-immune diseases were associated with the inhibitor only in 25 p. 100 of cases (mainly systemic lupus erythematosus). Thrombosis (venous, arterial or both) was found in 26 p. 100 of cases when auto-immune diseases were present and in 13.5 p. 100 of cases in the absence of these diseases. Spontaneous abortion was observed in 42 p. 100 of the women when the anticoagulant occurred in the course of an auto-immune disease and in 4 p. 100 when another or no underlying disease were identified. False-positive VDRL and thrombocytopenia were found associated with LA mainly in auto immune diseases. Anticardiolipin antibodies were positive in 37 p. 100 of 32 patients without any difference between auto-immune diseases and other pathologies. These results show that the "lupus anticoagulant" is a frequent coagulation abnormality even when auto-immune diseases are absent. The differences observed between auto-immune diseases and other pathologies in respect to clinical manifestations and biological findings associated with lupus anticoagulant suggest that the so-called "lupus anticoagulant" represents a group of antibodies with probably different specificities but which act in a similar manner in "in vitro" coagulation tests.

Abortion, Spontaneous↗