Search PubMed⌕ Search

Biomedical subjects

M Bernstein

Publications and source records attributed to M Bernstein.

At least 181 records · Page 10Linked to original sources
PubMed1990

Recombinant IL-4 inhibits IL-6 synthesis by adherent peripheral blood cells in vitro.

IL-4 has been shown to participate in interregulatory networks with other cytokines including IL-2, IFN-gamma, IL-1 beta, and TNF-alpha. The ability of recombinant IL-4 (rIL-4) to modulate the synthesis and release of IL-6 was investigated in vitro. LPS-stimulated adherent cells (AC) from human peripheral blood secreted IL-6 as determined by ELISA and bioassay with the B9 hybridoma cell line. The secretion of IL-6 peaked between 12-16 h after LPS stimulation. The addition of rIL-4 inhibited LPS-induced IL-6 production measured at 8 h. The inhibitory effect of rIL-4 on IL-6 secretion was dose-dependent and occurred at doses as low as 0.001 U/ml (0.01 pg/ml). Recombinant IL-4 was added to the cultures for various periods and removed by aspiration of the medium and washing the cells. The subsequent LPS-induction of IL-6 secretion was reduced in cultures exposed to rIL-4 for as little as 5 minutes indicating that the effect of rIL-4 on the monocytes was rapid and irreversible. Northern blot analysis revealed that the effect of rIL4 on LPS-induced production of IL-6 by AC occurred at least in part at the level of transcription. In contrast, PMA-induced IL-6 gene transcription was not affected by rIL-4. These findings indicate that rIL-4 can regulate the synthesis of IL-6 by adherent peripheral blood mononuclear cells.

Acute-Phase Reaction↗
PubMed1989

Evening urine cortisol excretion and DST results in depression and anorexia nervosa.

Cortisol determination in a single one-hour urine sample collected between 2200 h and 2300 h has been shown to identify accurately patients with Cushing's disease. To examine the usefulness of this procedure for identifying psychiatric patients with a pituitary-adrenal disturbance, we studied 17 drug-free depressed patients, 6 euthymic anorectic patients and 10 healthy volunteers. We found that there was good agreement between DST results and evening urine cortisol excretion in this sample (when cortisol levels were expressed as ng of cortisol per mg of creatinine), and that adopting as a criterion a urine cortisol value two standard deviations above the mean cortisol value of the controls predicts 74% of the dexamethasone suppression test (DST) results. We would like to suggest that this measure deserves further study as a potentially useful and simple alternative to the DST for identifying psychiatric patients with a pituitary-adrenal disturbance.

Adolescent↗
PubMed1989

Sec59 encodes a membrane protein required for core glycosylation in Saccharomyces cerevisiae.

When incubated at a restrictive temperature, Saccharomyces cerevisiae sec59 mutant cells accumulate inactive and incompletely glycosylated forms of secretory proteins. Three different secretory polypeptides (invertase, pro-alpha-factor, and pro-carboxypeptidase Y) accumulated within a membrane-bounded organelle, presumably the endoplasmic reticulum, and resisted proteolytic degradation unless the membrane was permeabilized with detergent. Molecular cloning and DNA sequence analysis of the SEC59 gene predicted an extremely hydrophobic protein product of 59 kilodaltons. This prediction was confirmed by reconstitution of the sec59 defect in vitro. The alpha-factor precursor, which was translated in a soluble fraction from wild-type cells, was translocated into, but inefficiently glycosylated within, membranes from sec59 mutant cells. Residual glycosylation activity of membranes of sec59 cells was thermolabile compared with the activity of wild-type membranes. Partial restoration of glycosylation was obtained in reactions that were supplemented with mannose or GDP-mannose, but not those supplemented with other sugar nucleotides. These results were consistent with a role for the Sec59 protein in the transfer of mannose to dolichol-linked oligosaccharide.

Amino Acid Sequence↗
PubMed1989

Vinblastine, cisplatin and bleomycin as salvage therapy for refractory high-risk metastatic gestational trophoblastic disease.

Vinblastine, cisplatin and bleomycin (VPB) were utilized as salvage therapy in seven women with high-risk metastatic gestational trophoblastic tumors resistant to prior treatment with triple therapy (methotrexate, actinomycin D and cyclophosphamide) or the modified Bagshawe protocol. While four patients (57%) achieved sustained remission with VPB, surgery was performed on two of them to remove sites of resistant disease. The mean prognostic score for the patients who achieved remission was 10 versus 17 for those who died (P less than .05). Although severe hematologic toxicity occurred in five patients (71%), no deaths were attributable to toxicity. Since VPB has limited activity when used as salvage therapy, alternate chemotherapy protocols need to be developed for patients with refractory gestational trophoblastic disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Human chorionic gonadotropin and free subunits' serum levels in patients with partial and complete hydatidiform moles.

Serum levels of hCG and its free subunits were measured in patients with partial and complete hydatidiform moles and in women with normal 10-week pregnancies. whereas complete moles had higher levels of percent-free beta-hCG than partial moles (2.4 versus 1.0; P less than or equal to .005), partial moles had higher levels of percent-free alpha-hCG than complete moles (0.85 versus 0.17; P less than or equal to .005). Normal 10-week pregnancies had lower levels of both percent-free beta-hCG and percent-free alpha-hCG than partial moles (0.40 versus 1.0, P less than or equal to .005 and 0.27 versus 0.85, P less than or equal to .005, respectively). Percent-free beta-hCG and beta-hCG levels did not distinguish which patients with complete mole were more likely to develop persistent post-molar tumor. The trophoblastic cells in complete and partial moles differ significantly in the manner in which they secrete the free subunits of hCG.

Chorionic Gonadotropin↗
PubMed1989

Tranexamic acid in the treatment of Kasabach-Merritt syndrome in infants.

Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy, and, occasionally, microangiopathic hemolysis) is an infrequent but often lethal complication of giant capillary hemangiomas in the infant. We report the clinical course of an infant who came to us with this syndrome shortly after birth. She was successfully treated with transfusions of blood products, high-dose oral prednisone, and a fibrinolytic inhibitor, tranexamic acid. No complications of the treatment occurred. The hematological abnormalities resolved completely by 2 years of age. Although prednisone may have been necessary for stabilization and involution of the hemangioma, the addition of tranexamic acid allowed earlier tapering of the steroid therapy and fewer transfusions. Tranexamic acid was extremely well tolerated in this newborn.

Cyclohexanecarboxylic Acids↗
PubMed1988

Characterization of a component of the yeast secretion machinery: identification of the SEC18 gene product.

SEC18 gene function is required for secretory protein transport between the endoplasmic reticulum (ER) and the Golgi complex. We cloned the SEC18 gene by complementation of the sec18-1 mutation. Gene disruption has shown that SEC18 is essential for yeast cell growth. Sequence analysis of the gene revealed a 2,271-base-pair open reading frame which could code for a protein of 83.9 kilodaltons. The predicted protein sequence showed no significant similarity to other known protein sequences. In vitro transcription and translation of SEC18 led to the synthesis of two proteins of approximately 84 and 82 kilodaltons. Antisera raised against a Sec18-beta-galactosidase fusion protein also detected two proteins (collectively referred to as Sec18p) in extracts of 35S-labeled yeast cells identical in size to those seen by in vitro translation. Mapping of the 5' end of the SEC18 mRNA revealed only one major start site for transcription, which indicates that the multiple forms of Sec18p do not arise from mRNAs with different 5' ends. Results of pulse-chase experiments indicated that the two forms of Sec18p are not the result of posttranslational processing. We suggest that translation initiating at different in-frame AUG start codons is likely to account for the presence of two forms of Sec18p. Hydrophobicity analysis indicated that the proteins were hydrophilic in nature and lacked any region that would be predicted to serve as a signal sequence or transmembrane anchor. Although potential sites for N-linked glycosylation were present in the Sec18p sequence, the sizes of the in vivo SEC18 gene products were unaffected by the drug tunicamycin, indicating that Sec18p does not enter the secretory pathway. These results suggest that Sec18p resides in the cell cytoplasm. While preliminary cell fractionation studies showed that Sec18p is not associated with the ER or Golgi complex, association with a 100,000 x g pellet fraction was observed. This suggests that Sec18p may bind transiently to small vesicles such as those presumed to participate in secretory protein transport between ER and the Golgi complex.

Amino Acid Sequence↗
PubMed1988

Acute subdural hematoma from ruptured posterior communicating artery aneurysm.

Acute spontaneous subdural hematoma is infrequent in association with rupture of intracranial saccular aneurysm. In the majority of cases, aneurysms of the middle cerebral artery along the convexity or of the anterior cerebral artery along the interhemispheric fissure are found to be the culprits. We present two recent cases of internal carotid-posterior communicating artery aneurysms causing acute subdural hematoma with little or no subarachnoid hemorrhage and discuss the possible mechanisms for this occurrence.

Acute Disease↗
PubMed1988

Symptomatic arterial luminal narrowing presenting months after subarachnoid hemorrhage and aneurysm clipping.

The authors describe three cases of clinical cerebral ischemia associated with angiographic evidence of cerebral arterial luminal narrowing presenting 7, 14, and 52 weeks after subarachnoid hemorrhage (SAH) and aneurysm clipping. Delayed vasospasm, in its usual time setting 1 or 2 weeks after hemorrhage, did not occur symptomatically in these patients. No evidence for aneurysm clip migration or rebleed was present. All patients responded favorably to volume expansion and elevation of blood pressure. This unusual occurrence of a very delayed vasospasm may further the understanding of the vasospastic process. The symptomatic onset of arterial luminal narrowing months after SAH may suggest that a proliferative vasculopathy more accurately explains the observed vessel narrowing, rather than conventional active constriction of vascular smooth muscle.

Adult↗
PubMed1987

Corticosteroid (methylprednisolone sodium succinate) pulse therapy in five dogs with autoimmune skin disease.

Corticosteroid pulse therapy is the parenteral administration of suprapharmacologic doses of methylprednisolone sodium succinate for short periods. Five dogs diagnosed as having autoimmune skin disease were treated, using pulse therapy, with subsequent dramatic and rapid improvement of skin lesions. The dogs had no adverse clinical signs attributable to the treatment. All dogs had a relapse of clinical signs after a maintenance protocol (0.5 mg/kg, q 48 h) of orally administered prednisone was started. Skin lesions on 4 of 5 dogs eventually were controlled by prednisone, azathioprine, or gold therapy.

Animals↗
PubMed1987

Product of SEC53 is required for folding and glycosylation of secretory proteins in the lumen of the yeast endoplasmic reticulum.

Yeast secretory mutant sec53 cells accumulate inactive secretory glycoprotein precursors that remain associated with the endoplasmic reticulum (ER) at the restrictive temperature (37 degrees C). The possibility that precursor polypeptides fail to penetrate completely into the ER lumen was tested by examining the protease accessibility of accumulated invertase, mating pheromone precursor prepro-alpha-factor and the vacuolar protein precursor procarboxypeptidase Y in cell lysates. In all three cases, the secretory protein precursors are protected from the action of exogenous protease unless the membrane is permeabilized by including Triton X-100 or saponin in the incubation. These results suggest that the sec53 defect allows complete polypeptide translocation. Consistent with this interpretation, the precursor of invertase accumulates in a signal peptide-processed form. In addition, invertase and prepro-alpha-factor precursors contain a small amount of possibly aberrant carbohydrate. In mutant cells or in wild type cells treated with tunicamycin, a 10-kDa fragment of the N terminus of mature invertase assumes a conformation that is resistant to trypsin with or without detergent. This domain may be associated with an ER protein or may simply assume an unusual conformation as a consequence of deficient glycosyl modification.

Carboxypeptidases↗
PubMed1987

Feasibility of chemical screening of urine for neuroblastoma case finding in infancy in Quebec.

Neuroblastoma is the most common fatal solid tumour of childhood. Studies in Japan suggest that screening urine at 6 months for tumour-derived metabolites greatly improves early case finding and prognosis. The incidence rate of neuroblastoma in Quebec is at least 1 per 10,330 live births, higher than that of all other diseases responding to early treatment except congenital hypothyroidism screened for in the Quebec Network of Genetic Medicine. The feasibility of chemical screening of urine for elevated levels of homovanillic acid and vanillylmandelic acid in Quebec was assessed. The cost-effectiveness of screening 100,000 infants per year would be high (cost-benefit ratio 2.4), with a net saving of about $280,000 and eight lives per year. The estimated cost of adding neuroblastoma screening to the existing urine metabolite screening program is $70,700. The apparent sensitivity of the proposed test is 0.859 and the rate of false-positive results about 0.1%, both acceptable values. The attitude of potential participants toward the present urine screening program and the addition of a "tumour test" was positive. The results indicate that a pilot study of neuroblastoma screening in Quebec could be undertaken.

Attitude to Health↗