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M Goldberg

Publications and source records attributed to M Goldberg.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Asbestos and risk of cancer: exposure-effect relationships for occupationally exposed populations].

For high levels of exposure (> 1 f/ml), the risk of lung cancer increases linearly with the cumulative exposure, and is the same for all types of asbestos; the risk of mesothelioma increases linearly with the level of exposure, is time dependent and higher for amphiboles. The effects of asbestos and smoking for lung cancer are independent, and the probability that a cancer is due to asbestos is the same among smokers and non-smokers. There is no scientific method for quantifying directly the risks associated to low levels of exposure (< 1 f/ml). The only possible approach is to extrapolate from the risks observed at high levels to low levels. Proportionality without threshold between dose and risk is not certain, but is the most plausible model. Using this model, one can expect about 30 additional cases of cancer for 10,000 men exposed at the level of 0.1 f/ml from 20 to 65 years, and about 16 additional cases for 10,000 women. These are high figures compared to other health hazards.

Adult↗
PubMed1998

H-7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells.

Protein kinase inhibitor H-7 was reported to stimulate desmosome formation in normal keratinocytes and to inhibit proliferation of neural cell lines. In the present study, the effects of this inhibitor on adhesion and growth of KB human oral carcinoma cells were investigated. H-7 was found to enhance desmosome assembly, as evidenced by an increased punctate labeling for the major desmosomal markers. Immunogold labeling confirmed the formation of desmosomes both at the cell surface and in the cytoplasm. In order to assess cell proliferation and possible correlation with adhesion, confluent cultures were treated and both adherert and detached cell fractions were counted. Under serum-free conditions, H-7 significantly reduced cell detachment. In contrast, EGF stimulated cell detachment, and this effect was abolished when cells were simultaneously treated with both EGF and H-7. Total cell counts were also significantly reduced by H-7, both in the presence and absence of EGF. Using the TUNEL technique, labeled cells were increased after H-7 treatment, thus implicating protein kinase inhibition in cell death. These results indicate that H-7 inhibits growth and stimulates adhesion of KB carcinoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Treatment of feline leukemia virus-infected cats with paramunity inducer.

Two placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of the paramunity inducer, Baypamun in feline leukemia virus (FeLV)-infected cats under controlled conditions. In the first study, 120 cats were involved; 60 cats were treated with Baypamun and 60 with a placebo preparation of virus-free cell culture medium. Dosage and administration of the drug over a 7-week period were performed according to the instructions given by the company. Remission of viremia occurred in 12% and 7% of the cats treated with Baypamun and placebo, respectively. This difference was not statistically significant. In the second study, 30 naturally infected cats were treated in a placebo-controlled double-blind trial. In total, 20 immunological, clinical, laboratory, and virological parameters were examined. No statistically significant differences could be demonstrated between Baypamun and placebo application. Therefore, FeLV infection was not influenced by Baypamun treatment.

Adjuvants, Immunologic↗
PubMed1998

Progesterone withdrawal. II: insensitivity to the sedative effects of a benzodiazepine.

Previous results from this lab have demonstrated that the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) exhibits withdrawal properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897-904.] and seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J. M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we have demonstrated that withdrawal from P produces insensitivity to the potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl- current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M. H. ffrench-Mullen, Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74 (1995) 464-469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.], assessed using whole cell patch clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. The purpose of the present study was to examine the withdrawal effects of P on the sedative potency of LZM, tested behaviorally as the ability to maintain position on a variable speed treadmill following LZM administration (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal) as well as discontinuous (multiple P injection, multiple withdrawal) paradigms were tested. Longer continuous release paradigms were more effective in abolishing the sedative effects of LZM, without producing a change in baseline response. The LZM insensitivity observed following the multiple withdrawal paradigm was prevented by prior intraventricular administration of antisense oligonucleotide against the alpha4 subunit of the GABAA receptor. These results support the hypothesis that withdrawal from P decreases the behavioral response to LZM as a direct result of increases in the alpha4 subunit of the GABAA receptor. Withdrawal from P occurs endogenously during pre-menstrual and post-partum periods, when decreased response to BDZ has been reported.

Analysis of Variance↗
PubMed1998

Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus.

The acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated for their efficacy and side effects in a double-blind placebo-controlled trial using naturally occurring feline immunodeficiency virus (FIV)-infected cats. This natural retrovirus animal model is considered highly relevant for the pathogenesis and chemotherapy of HIV in humans. Both PMEA and FPMPA proved effective in ameliorating the clinical symptoms of FIV-infected cats, as measured by several clinical parameters including the incidence and severity of stomatitis, Karnofsky's score, immunologic parameters such as relative and absolute CD4+ lymphocyte counts, and virologic parameters including proviral DNA levels in peripheral blood mononuclear cells (PBMC) of drug-treated animals. In contrast with PMEA, FPMPA showed no hematologic side effects at a dose that was 2.5-fold higher than PMEA.

Adenine↗
PubMed1998

Effects of inositol hexasulphate, a casein kinase inhibitor, on dentine phosphorylated proteins in organ culture of mouse tooth germs.

To study the effects of impaired protein phosphorylation on dentine formation and mineralization, inositol hexasulphate, an intracellular type I and type II casein kinase inhibitor, was used in an in vitro organotypic culture system. Mandibular first molar tooth germs were dissected from 18-day-old mouse embryos and cultured for 11 days with and without inositol hexasulphate at different concentrations. At 0.04-0.08 mM inhibitor, cellular alterations were not detected. Dentine displayed the characteristic purple-blue colour when Stains all, a specific stain for extracellular phosphoproteins, was used. At 0.1 mM, dentine failed to stain and mineralization did not occur, as seen from the von Kossa method. The presence of numerous lysosome-like vesicles inside cells indicated that the experiment was at the limits of cytotoxicity; higher concentrations induced severe cellular alterations. Therefore, quantitative radioautography was carried out on germs treated or not with the inhibitor at 0.1 mM. [33P]-phosphate incorporation showed that grain density in inhibited germs compared with that in control germs was about double in odontoblasts and half in the predentine/dentine compartment. In the presence of inositol hexasulphate the incorporation of [3H]serine into odontoblast cell bodies was unchanged between 2 and 24 h while in predentine/dentine, grain density was higher between 1 and 4 h, and reduced at 24 h. Both with [33P]phosphate and [3H]serine, labelling was seen throughout the porous dentine formed in vitro and not as a band located at the predentine/dentine junction, as is the case in vivo. With [3H]proline, in the presence of the inhibitor, a small reduction of grain density occurred in cell bodies, no significant difference was seen between 1 and 4 h in predentine/dentine, and more silver grains were present after 24 h both in cells and in the matrix. The radioautographic data support the view that the inhibitor interacts mostly with post-transductional phosphorylation and does not alter significantly other cell synthetic pathways and functions. Finally, the experiments presented here confirm that phophorylated proteins have a key role in dentine mineralization.

Analysis of Variance↗
PubMed1998

Quantitative immunohistochemical evidence of a functional gradient of chondroitin 4-sulphate/dermatan sulphate, developmentally regulated in the predentine of rat incisor.

A quantitative examination was carried out on the early and mature stages of dentinogenesis in the rat incisor, using a post-embedding immunogold labelling with an anti-chondroitin 4 sulphate/dermatan sulphate antibody (2B6). At a very early stage of predentine formation, before polarizing odontoblasts have established junctional complexes, immunolabelling was weak. In contrast, when polarized odontoblasts established distal junctional complexes, immunolabelling in predentine was uniform and threefold denser than in initial predentine. The same gold particle density was found in the non-mineralized mantle dentine. During circumpulpal dentine formation, a gradient was seen in predentine, a larger number of gold particles being scored in the proximal zone compared with the distal region adjacent to the mineralization front. In circumpulpal dentine, some labelling was found within the lumen of the tubules and in the bordering dentine around the tubules. A few particles were also detected in intertubular matrix after demineralization. Together, these data provide evidence for a developmentally regulated gradient during the transition between mantle and circumpulpal dentine, and also in a more mature part of the tooth, a functional gradient that probably plays a role in the process of mineralization.

Animals↗
PubMed1998

Regional disparities in cardiovascular risk factors in France: a five-year analysis of the GAZEL cohort.

OBJECTIVES: the study was set up to explore regional disparities in France in the annual prevalence of cardiovascular risk factors (hypertension, high lipids, obesity, diabetes and tobacco consumption) and protective factors (alcohol intake) in members of the GAZEL Cohort and to determine which, if any, risk factors followed the same north-south gradient as the one known for cardiovascular mortality. METHODS: the population studied comprised 18,070 subjects aged from 35 to 50 years, employed by the French national gas and electricity company. Every year from 1989 to 1993 they received a self-administered questionnaire by mail. From the replies, differences in risk factor prevalence were evaluated by an odds ratio adjusted for sex and age, using a marginal model. RESULTS: a regional effect was found (p < 0.001) for arterial hypertension, with high odds ratios in northern France and low ratios in the south east, for high lipids, with high odds ratios in Champagne, the Loire region and Upper Normandy and low ratios in the south east and the Paris area, and for obesity, with high odds ratios in the north and north east and low ratios in the south, south east and west. CONCLUSION: these results show a gradient between the north and south east for hypertension, obesity, and to a lesser degree high lipids. This gradient corresponds to the known regional disparities for cardiovascular mortality.

Adult↗
PubMed1998

Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group.

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

Female↗
PubMed1998

Interactions among Drosophila nuclear envelope proteins lamin, otefin, and YA.

The nuclear envelope plays many roles, including organizing nuclear structure and regulating nuclear events. Molecular associations of nuclear envelope proteins may contribute to the implementation of these functions. Lamin, otefin, and YA are the three Drosophila nuclear envelope proteins known in early embryos. We used the yeast two-hybrid system to explore the interactions between pairs of these proteins. The ubiquitous major lamina protein, lamin Dm, interacts with both otefin, a peripheral protein of the inner nuclear membrane, and YA, an essential, developmentally regulated protein of the nuclear lamina. In agreement with this interaction, lamin and otefin can be coimmunoprecipitated from the vesicle fraction of Drosophila embryos and colocalize in nuclear envelopes of Drosophila larval salivary gland nuclei. The two-hybrid system was further used to map the domains of interaction among lamin, otefin, and YA. Lamin's rod domain interacts with the complete otefin protein, with otefin's hydrophilic NH2-terminal domain, and with two different fragments derived from this domain. Analogous probing of the interaction between lamin and YA showed that the lamin rod and tail plus part of its head domain are needed for interaction with full-length YA in the two-hybrid system. YA's COOH-terminal region is necessary and sufficient for interaction with lamin. Our results suggest that interactions with lamin might mediate or stabilize the localization of otefin and YA in the nuclear lamina. They also suggest that the need for both otefin and lamin in mediating association of vesicles with chromatin might reflect the function of a protein complex that includes these two proteins.

Animals↗
PubMed1998

Psychosocial work environment and cardiovascular risk factors in an occupational cohort in France.

STUDY OBJECTIVE: Concordant results have been reported in several studies for the effects of job stress on cardiovascular disease, but the potential mechanisms of these effects have seldom been explored. The aim of this study was therefore to examine, in women and men, the cross sectional relations between psychosocial work variables (psychological demands, decision latitude, and social support) and cardiovascular risk factors (hypertension, hyperlipidaemia, diabetes, overweight, smoking, and alcohol consumption). PARTICIPANTS: The original cohort comprised 20,625 volunteers (men aged from 40 to 50 and women from 35 to 50) employed by the French Company Electricité De France-Gaz De France and followed up yearly since 1989. The study was restricted to the 13,226 volunteers in the cohort who were still working and answered a self administered questionnaire on psychosocial work factors in 1995. DESIGN: Data were based on replies to this questionnaire. Three psychosocial work environment exposure scores were used to assess psychological demands, decision latitude, and social support at work respectively. The main outcome measures were the prevalence of hypertension, hyperlipidaemia, and diabetes within the previous 12 months, overweight, smoking, and alcohol consumption. MAIN RESULTS: Psychosocial work factors were significantly associated with hypertension, hyperlipidaemia, overweight, smoking, and alcohol consumption, but not with diabetes. In men, low decision latitude was associated with hypertension, high decision latitude and high social support with overweight, low decision latitude with alcohol consumption. Moreover, the risk of hyperlipidaemia increased in men exposed to both high psychological demands and low social support. In women, low decision latitude was related to hyperlipidaemia, high psychological demands with overweight, high psychological demands and high decision latitude with smoking, and low social support with alcohol consumption. CONCLUSIONS: These cross sectional results underline the potential effects of psychosocial work characteristics on cardiovascular risk factors and the differences between the effects of job stress in men and women, and confirm the direct mechanisms (through physiological variables) and indirect mechanisms (through behavioural risk factors) potentially involved in the relation between psychosocial work characteristics and cardiovascular disease.

Adult↗
PubMed1998

Psychosocial factors at work and sickness absence in the Gazel cohort: a prospective study.

OBJECTIVE: To test whether psychosocial factors at work are predictors of rates of sickness absence. METHODS: The study population consisted of middle aged men and women employed by the French national electricity and gas company (EDF-GDF) in various occupations and followed up since 1989 by annual self administered questionnaires and independent data obtained from the medical and personnel departments of EDF-GDF. The 1995 questionnaire provided information about three psychosocial work factors: psychological demands, decision latitude, and social support at work. Sick-ness absence data were provided by the company's social security department. The occurrence of spells and days of absence in the 12 months after completion of the 1995 questionnaire was studied. Potential confounding variables were age, smoking, alcohol, and marital status, assessed in the 1995 questionnaire, and educational level and occupation, assessed from data provided by the personnel department. This study was restricted to the 12,555 subjects of the initial cohort who were still working and answered the self administered questionnaire in 1995. RESULTS: Low levels of decision latitude were associated with more frequent and longer sickness absences among men and women. Low levels of social support at work increased the numbers of spells and days of absence among men only. These associations weakened after adjustment for potential confounding factors, but remained significant. CONCLUSION: The study indicates that psychosocial factors at work, especially decision latitude, are predictive of sickness absence.

Adult↗
PubMed1998

Psychosocial factors at work and subsequent depressive symptoms in the Gazel cohort.

OBJECTIVE: This study attempted to establish whether psychosocial factors at work are predictors of depressive symptoms in a prospective cohort of men and women employed in a wide variety of occupations by the French national company Electricité De France - Gaz De France (EDF-GDF). METHODS: This prospective cohort study followed the Gazel cohort by means of annual self-administered questionnaires and independent data obtained from the medical and personnel departments of the company. The self-administered questionnaire, in 1995, provided information about the psychosocial work environment characteristics, psychological job demands, decision latitude, and social support at work. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) Scale in the 1996 questionnaire. Potential confounding variables were age, marital status, and number of children, assessed in the 1995 questionnaire, stressful personal and occupational events during the previous 12 months, assessed in the 1996 questionnaire, and educational level, occupation and previous absenteeism for mental disorders, assessed from the independent data provided by EDF-GDF. The subjects were 11 552 workers (8422 men aged 46-56 years in 1995 and 3130 women aged 41-56 years) who answered the 1995 and 1996 questionnaires and were working during this period. RESULTS: High levels of psychological demands, low levels of decision latitude, and low levels of social support at work were significant predictors of subsequent depressive symptoms in both the men and the women. These results were unchanged after adjustment for potential confounding variables. CONCLUSIONS: The results strongly support the possibility that psychosocial factors at work are predictive of depressive symptoms.

Adaptation, Psychological↗
PubMed1997

Hypoxia alters the subcellular distribution of protein kinase C isoforms in neonatal rat ventricular myocytes.

Cardiac myocytes coexpress multiple protein kinase C (PKC) isoforms which likely play distinct roles in signaling pathways leading to changes in contractility, hypertrophy, and ischemic preconditioning. Although PKC has been reported to be activated during myocardial ischemia, the effect of ischemia/hypoxia on individual PKC isoforms has not been determined. This study examines the effect of hypoxia on the subcellular distribution of individual PKC isoforms in cultured neonatal rat ventricular myocytes. Hypoxia induces the redistribution of PKC alpha and PKC epsilon from the soluble to the particulate compartment. This effect (which is presumed to represent activation of PKC alpha and PKC epsilon) is detectable by 1 h, sustained for up to 24 h, and reversible within 1 h of reoxygenation. Inhibition of phospholipase C with tricyclodecan-9-yl-xanthogenate (D609) prevents the hypoxia-induced redistribution of PKC alpha and PKC epsilon, whereas chelation of intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) blocks the redistribution of PKC alpha, but not PKC epsilon; D609 and BAPTA do not influence the partitioning of PKC alpha and PKC epsilon in normoxic myocytes. Hypoxia, in contrast, decreases the membrane association of PKC delta via a mechanism that is distinct from the hypoxia-induced translocation/activation of PKC alpha/PKC epsilon, since the response is slower in onset, slowly reversible upon reoxygenation, and not blocked by D609 or BAPTA. The hypoxia-induced shift of PKC delta to the soluble compartment does not prevent subsequent 4-beta phorbol 12-myristate-13-acetate-dependent translocation/activation of PKC delta. Hypoxia does not alter the abundance of any PKC isoform nor does it alter the subcellular distribution of PKC lambda. The selective hypoxia-induced activation of PKC isoforms through a pathway involving phospholipase C (PKC alpha/PKC epsilon) and intracellular calcium (PKC alpha) may critically influence cardiac myocyte contractility, gene expression, and/or tolerance to ischemia.

Animals↗