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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 91 records · Page 5Linked to original sources
PubMed1993

The appearance of Kaposi sarcoma during corticosteroid therapy.

BACKGROUND: Four epidemiologic types of Kaposi sarcoma (KS) are known: classic KS, endemic African KS, epidemic or acquired immunodeficiency syndrome-related KS, and KS associated with immunosuppressive therapy. In most of the latter patients, KS was reported to have developed after organ transplantation, particularly renal transplantation. Thirty-nine patients who have not had a transplant have been reported to have KS associated with corticosteroid therapy. METHODS: The authors studied 10 patients with the appearance of KS during corticosteroid therapy (6 men, 4 women; age range, 42-79 years) who were treated with corticosteroids for autoimmune disorders (5 patients), lymphoproliferative disorders (2 patients), and diseases unrelated to the immune system (3 patients). RESULTS: Genetically programmed susceptibility to corticosteroid-related KS was suggested by the descent of the study patients as well as most of those reported previously. The prognosis was guarded in all the study patients. CONCLUSIONS: Corticosteroids should be withdrawn to achieve clinical remission.

Adult↗
PubMed1993

In vitro activation of the transcription factor ISGF3 by interferon alpha involves a membrane-associated tyrosine phosphatase and tyrosine kinase.

Interaction of interferon alpha (IFN alpha) with its cell surface receptor rapidly activates the formation of the transcription complex ISGF3, which subsequently translocates to the nucleus and stimulates the expression of a variety of early response genes. We have recently developed a cell-free system where IFN alpha can activate the formation of ISGF3 in vitro. This system has enabled us to demonstrate that the component of the ISGF3 transcription complex which is modified by IFN alpha treatment (ISGF3 alpha) is membrane-associated and that its activation involves a protein kinase. Using a combination of specific tyrosine kinase and phosphatase inhibitors and monoclonal anti-phosphotyrosine antibodies we now are able to demonstrate that IFN alpha-activated transcription involves at least a two-step process where a membrane-associated tyrosine phosphatase and a tyrosine kinase lead to modification of ISGF3 alpha and subsequent formation of the complete complex. Furthermore, formation of the ISGF3 complex is specifically disrupted by protein tyrosine phosphatase and can be reversibly dissociated by the phosphotyrosine analogue phenylphosphate. The latter observation suggested that SH2 and/or SH3 domains may be required for the stable formation of this transcription complex.

Base Sequence↗
PubMed1993

Effects of the antioxidant butylated hydroxyanisole on cytosolic free calcium concentration.

The effect of the antioxidant butylated hydroxyanisole on free intracellular calcium was investigated in rat cardiomyocytes, rat pituitary cells, human umbilical vein endothelial cells, granulocytes and BHK-cells. The effects of incubation time and butylated hydroxyanisole (BHA) concentrations were examined with respect to the extracellular calcium concentration. Butylated hydroxyanisole increased the free cytosolic calcium concentration in a dose- and time-dependent manner irrespective of the presence of extracellular calcium. Differences between all cell types were observed in the sequel of the re-uptake of the calcium ions released by BHA. Dependence on the concentration of extracellular calcium on the extent of sequestration was seen in rat pituitary cells and cardiomyocytes only.

Animals↗
PubMed1993

Dose-dependent induction or depression of cysteine conjugate beta-lyase in rat kidney by N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine.

The influence of N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine (NAc-PCBD) on cysteine conjugate beta-lyase in female rat kidney has been examined. After a single, non-nephrotoxic dose of NAc-PCBD (3 mg/kg), cytosolic beta-lyase enzyme activity was increased 1.5 to 3-fold commensurate with a corresponding increase in enzyme protein levels as assessed by both Western blot and ELISA analyses. Using a cDNA probe for beta-lyase, this induction was found to be accompanied by an increase in the cognate mRNA. In contrast, a higher, nephrotoxic dose of NAc-PCBD (10 mg/kg) decreased all the above parameters. These effects appeared to be specific to the cytosolic form of the enzyme as no changes in kidney mitochondrial beta-lyase or enzyme protein levels were observed. Repeated dosing with the lower dose level (3 mg/kg) resulted in either no change, or in some instances, a reduction in the above parameters, suggesting an accumulation of the xenobiotic and a masking of the induction phenomenon. The molecular mechanisms underlying these observations are discussed in terms of the nephrotoxicity of halogenated xenobiotics.

Acetylcysteine↗
PubMed1993

Sensory evaluation and nutrient composition of weaning food from pregelatinized maize-sweet potato mixtures.

Pregelatinized maize-sweet potato mix, fortified with soybeans and groundnut flours, was evaluated for its acceptability as a weaning food and for nutrient composition. An acceptable product had 14.3, 6.4, 2.4 and 67.4%, respectively, for its protein, fat, ash and carbohydrate contents. Values for calcium, phosphorus and and iron contents were 59.6, 187.5 and 2.4 mg/100 g, respectively, while the most predominant fatty acids were linoleic, oleic and palmitic acids. The product, which had a chemical score of 85.34 for its protein value, was limiting in threonine.

Calcium↗
PubMed1993

Quantitative and qualitative assessment of plasma von Willebrand factor in classic Kaposi's sarcoma.

BACKGROUND: von Willebrand factor (vWF) is synthesized almost exclusively by endothelial cells and is stored there as ultra-high-molecular-weight multimers. The vWF multimers that are detected in the plasma are smaller than those stored within the endothelium. In two previous studies, comprising small series of cases with classic Kaposi's sarcoma (KS), an endothelium-derived tumor, increased levels of plasma von Willebrand factor antigen (VWF:Ag, the antigenic structure) were reported, suggesting that vWF:Ag may be a marker of endothelium proliferation. OBJECTIVE: Our purpose was to investigate the quantitative as well as qualitative alterations of plasma vWF in a large series of patients with classic KS at various stages of the disease. METHODS: Levels of plasma vWF:Ag were studied in 38 patients with classic KS confined to the skin at various stages of the disease and compared with a control group. Thirty-three patients had active KS (i.e., with skin lesions) and five were in remission. In five patients with active KS multimeric analysis of plasma vWF was also performed. RESULTS: The levels of vWF:Ag were significantly higher among KS patients than in the control group (n = 29, p < 0.01). Levels of vWF:Ag were also significantly higher in patients with active disease as compared with those in remission (p < 0.05). No correlation was found between vWF:Ag levels and the extent of KS. Analysis of the multimeric pattern of plasma vWF showed enhanced staining of all bands, particularly the intermediate and high molecular weight forms, which resemble the endothelial forms as opposed to normal circulating vWF multimers. CONCLUSION: Quantitative as well as qualitative alterations in plasma vWF were found in patients with KS, which may reflect the destruction or activation of endothelial cells within the lesions. vWF:Ag may serve as a marker of disease activity in classic KS; however, it is not a good marker for the extent of the disease.

Aged↗
PubMed1993

Kaposi's sarcoma with visceral involvement after intraarticular and epidural injections of corticosteroids.

Kaposi's sarcoma has been reported in patients receiving immunosuppressive therapy, most of whom are organ transplant recipients. The development of Kaposi's sarcoma after treatment with corticosteroids has been reported in only 38 patients who have not had acquired immunodeficiency syndrome or undergone organ transplantation. Cutaneous Kaposi's sarcoma developed 2 months after intraarticular steroid injections in a man with ulnar nerve entrapment. The lesions regressed spontaneously after 3 months but reappeared with visceral involvement 18 months later, shortly after initiation of a course of epidural steroid injections for treatment of low back pain. The cutaneous lesions and some visceral lesions rapidly regressed after cessation of treatment.

Administration, Topical↗
PubMed1993

Prenatal diagnosis and treatment of 21-hydroxylase deficiency.

Prenatal diagnosis of 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia (CAH), has benefited from the advances in endocrinologic and molecular genetic studies. In 1976, prenatal diagnosis of the disease was first attempted by measuring 17-hydroxyprogesterone in the amniotic fluid in the second trimester of pregnancy. Discovery of a close linkage between HLA and the disease gave a second approach for prenatal diagnosis, the latter being made by linkage study of the haplotypes of the index case in a given family. Diagnosis was later made directly by molecular biology. Currently, the studies of the C4-CYP21B gene locus by Southern blotting and the CYP21B gene mutations by PCR methods simplify the diagnostic procedure of an early and accurate prenatal diagnosis in the first trimester. In these conditions all families are now informative. Moreover, using a direct genetic analysis associated with the possibility of detecting the heterozygotes in a non-related CAH population, a prenatal diagnosis can be done in a family without a previously CAH affected child. From our results in a series of 274 pregnancies at risk for CAH in whom prenatal diagnosis has been made by these different approaches, it can be concluded that steroid analysis in the amniotic fluid is an accurate method but provides only a late (second trimester) diagnosis, while an early and accurate diagnosis now relies on adequate molecular genetic studies on chorion villus biopsies. In the aim to prevent the virilization of the external genitalia in CAH female fetuses, prenatal treatment was instituted in our group in 1979 by giving dexamethasone to the mother. This prenatal treatment appears safe for the fetus and the child and is effective in preventing virilization of CAH affected females. Although the degree of prevention is not always complete in all cases, the advantages of prenatal treatment are prevailing over the complications observed in a few mothers.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Pregnancy loss and work schedule during pregnancy.

Shift work has been associated with many health complaints, but its relation with pregnancy loss has rarely been studied. We compared the work schedule during pregnancy of 331 women with a pregnancy loss with that of 993 pregnant women matched on gestational age. The risk of pregnancy loss was four times higher among women with fixed evening work schedules in comparison with women on a fixed day schedule (odds ratio = 4.17; 95% confidence interval = 2.19-7.92), and more than twice as high among those on a fixed night schedule (odds ratio = 2.68; 95% confidence interval = 0.53-13.43).

Cross-Sectional Studies↗
PubMed1993

The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma.

Interferon alpha-2a, which has antineoplastic, antiviral, immunomodulatory, and antiangiogenic effects, was evaluated in a prospective study, treating 10 lesions of patients with classical Kaposi's sarcoma. Ten patients received injections of interferon alpha-2a intralesionally in a dose of 3 million units three times weekly for 4 weeks, and in a variable dose for 4 more weeks. Two of the patients had a complete response, and in one of these, distant lesions also responded. Seven had a partial response, and one did not respond. The treatment was generally well tolerated. The results of our study support the use of interferon in the therapy of classical Kaposi's sarcoma, although it would appear that to achieve maximum efficacy, a longer period of treatment is needed.

Adult↗
PubMed1993

In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor.

Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin-2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose-dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment.

Adult↗
PubMed1993

Oxygen-regulated in vitro transcription of Rhizobium meliloti nifA and fixK genes.

Oxygen concentration regulates the expression of nitrogen fixation genes in the symbiotic bacterium Rhizobium meliloti. We demonstrate that two proteins, FixL and FixJ, that belong to the two-component family of regulatory proteins are necessary and sufficient for oxygen-regulated in vitro transcription of the two key regulatory genes, nifA and fixK. We show directly that FixJ is a transcriptional activator, working in conjunction with the RNA polymerase sigma 70 holoenzyme. Addition of FixL122, a soluble form of the sensor FixL protein, to the transcription assay enhanced FixJ transcriptional activity in response to low oxygen concentration. This enhancement of FixJ activity was correlated with FixJ phosphorylation.

Bacterial Proteins↗
PubMed1993

A nuclear tyrosine phosphatase downregulates interferon-induced gene expression.

Alpha and gamma interferons rapidly induce several early response genes in primary human diploid fibroblasts. The transcription rates of these genes are maximal after 1 h of interferon treatment and return to basal levels within 8 h. Three different interferon-activated DNA-binding complexes (ISGF3, GAF, and FcRF gamma) that are responsible for transcriptional activation of cellular genes have been characterized. Assembly of these complexes requires tyrosine phosphorylation of one or more of the protein components. In this report, we demonstrate that a nuclear tyrosine phosphatase is responsible for the deactivation of these interferon-regulated transcription factors and the subsequent transcriptional downregulation of the corresponding genes. Furthermore, tyrosine phosphorylation is required for nuclear localization of the 91-kDa protein that is part of all three interferon-induced transcription complexes. These results provide the first evidence for a nuclear tyrosine phosphatase activity as a mechanism of transcriptional regulation.

Base Sequence↗
PubMed1993

In vitro activation of the transcription factor gamma interferon activation factor by gamma interferon: evidence for a tyrosine phosphatase/kinase signaling cascade.

Although it has been well documented that the biological activities of gamma interferon (IFN-gamma) are initiated through interaction with its cell surface receptor, the signal transduction mechanisms which mediate the effects of this cytokine have remained unclear. In order to facilitate a better understanding of IFN-gamma signaling, we have designed an assay using human fibroblast cell homogenates in which IFN-gamma activates the formation of the IFN-gamma activation factor (GAF) transcription complex. GAF mediates the rapid transcriptional activation of the guanylate-binding protein gene by IFN-gamma. Activation of GAF in homogenates required ATP, but not Ca2+ or GTP. Fractionation of homogenates indicated that both the pellet (18,000 x g) and the remaining cytoplasmic fraction were required for GAF activation by IFN-gamma. In intact cells and cell homogenates, the activation of GAF was prevented by the specific tyrosine kinase inhibitor genistein. Treatment of GAF-containing nuclear extracts with either monoclonal antiphosphotyrosine antibody or protein tyrosine phosphatase prevented the assembly of the transcription complex, indicating that its formation required phosphorylation of tyrosine residues. Furthermore, the tyrosine phosphatase inhibitors phenylarsine oxide and zinc chloride also inhibited GAF formation in vitro, but only if these agents were added to cell homogenates before IFN-gamma was added. The addition of either agent 5 min after IFN-gamma had no effect. These results provide the first evidence for an IFN-gamma-regulated tyrosine phosphatase/kinase signaling cascade that permits this cytokine to activate the transcription of an early-response gene.

Antibodies, Monoclonal↗