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Biomedical subjects

M Goldberg

Publications and source records attributed to M Goldberg.

At least 109 records · Page 6Linked to original sources

Future trends in mortality of French men from mesothelioma.

OBJECTIVES: Previous projections of mortality from mesothelioma among French men have used the age-generation method, based on the Poisson regression model. In this study an alternative method to model mortality from mesothelioma was used to predict its future trend: this method was based on the risk function that links this mortality to past exposure to asbestos, combined with population exposure data. METHOD: Data on past French asbestos imports were used to model the overall past exposure to asbestos in men and assess two extreme scenarios (optimistic and pessimistic) for its future trends. The number of male deaths occurring between the ages of 50 and 79, from 1997-2050, was then calculated with the risk function for mesothelioma. RESULTS: The results showed that mortality from mesothelioma among French men aged 50-79 will continue to increase, reaching a peak averaging between 1140 (optimistic scenario) and 1300 deaths (pessimistic scenario) annually around the years 2030 and 2040, respectively. No preventive measures applied now will affect this trend before then. These results are similar to those of two other predictions of mortality from mesothelioma among French men: a peak around 2030 of 800-1600 deaths annually among men aged 25-89 years, and a peak around 2020 of 1550 deaths annually among men aged 40-84. CONCLUSIONS: Our results indicate that between 1997 and 2050, the most optimistic and pessimistic trends of future exposure will lead to the deaths from mesothelioma of between 44 480 and 57 020 men, with a corresponding loss of from 877 200 to 1 171 500 person-years of life.

Aged↗

Inositol hexasulphate, a casein kinase inhibitor, alters enamel formation in cultured embryonic mouse tooth germs.

Post-translational modification of enamel proteins is regulated by casein kinases (CK) and results in binding sites for calcium ions that subsequently play a key role during the initial stages of mineralization. Phosphorylation may also influence the secretion and extracellular organization of enamel proteins. Previous studies indicated that inositol hexasulphate inhibited the activity of CK-I and/or CK-II in mouse tooth germs (Torres-Quintana et al., 1998). We hypothesized that inositol hexasulphate would also inhibit the activity of the specific casein kinase(s) identified in secretory ameloblasts, and would prove useful for determination of the extent to which phosphorylation might influence the organization of enamel proteins at early stages of enamel formation. To test this hypothesis, we dissected mandibular first molars from 18-day-old mouse embryos and cultured them for 11 days in the presence of 0-0.1 mM inositol hexasulphate. Ultastructural analysis revealed that the formation of enamel was largely impaired at an inhibitor concentration > or = 0.08 mM. Quantitative radioautographic analysis of [33P]phosphate incorporation indicated that radiolabeled phosphate normally secreted into forming enamel was retained within ameloblasts. In contrast, no significant difference was observed between control and inositol-hexasulphate-treated tooth germs when cultures were labeled with [3H]serine and [3H]proline. SDS-PAGE and Western blot analysis confirmed that while inositol hexasulphate inhibited CK-mediated phosphorylation, it did not significantly alter protein synthesis. We conclude that impairment of phosphorylation leads to intracellular accumulation of [3H]phosphate-containing material by ameloblasts. We also conclude that when non-phosphorylated enamel matrix proteins are secreted, they are either unable to form an enamel matrix that supports mineralization, or they diffuse throughout a poorly mineralized dentin.

Ameloblasts↗

Brainstem auditory evoked response in newborns and infants.

Brainstem auditory evoked response studies were carried out on 105 neonates, with gestational ages ranging from 26 to 43 weeks. The mean chronologic and postconception ages of the subjects were 6.5 weeks and 40.6 weeks, respectively. Statistically significant relationships between brainstem auditory evoked response and gestational age, postconception age (gestational age plus chronologic age), and the 5-minute Apgar score, were demonstrated. Shortening of brainstem auditory evoked response as related to postconception age was demonstrated and this trend was statistically significant. However, of these factors a statistically significant shortening (maturation) of evoked response was demonstrated only in relation to postconception age.

Apgar Score↗

Asymmetric crying facies and associated congenital anomalies: prospective study and review of the literature.

Congenital asymmetric crying facies, a minor congenital anomaly due to absence or hypoplasia of the depressor anguli oris muscle on one side of the mouth, is associated at times with major congenital anomalies, most commonly in the cardiovascular system. In a prospective study of 5532 infants born at the Assaf Harofeh Medical Center, Israel, during 12 months (January to December 1998), 17 infants (an incidence of 0.31%) had asymmetric crying facies. One of the affected infants had ventricular septal defect and another infant had VATER (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia) syndrome. No noxious obstetric perinatal factors could be identified. Family history was unremarkable in all cases. Diagnostic work-up performed in all of the affected infants failed to reveal an additional congenital malformation. Asymmetric crying facies is a minor isolated finding in most of the cases; however, a thorough search for other congenital malformations, especially of the cardiovascular system, should be performed.

Crying↗

Androgen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study.

Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. However, the mechanisms of bone loss caused by androgen deficiency are still unclear. In the present study, we sequentially investigated the skeletal and hormonal effects of androgen deficiency in aged orchiectomized (ORX) rats over a time period of 9 months. One hundred seventy 13-month-old male Fischer-344 rats were either ORX or sham-operated (SHAM). Eight rats served as baseline controls. After in vivo fluorochrome labeling, groups of 8-15 SHAM and ORX rats each were killed at 2 weeks and at 1, 2, 3, 4, 6, and 9 months postsurgery. As expected, ORX induced a fall in serum total and free testosterone levels, but also reduced serum estradiol concentrations. Cancellous bone area (BAr) in the proximal tibia but not in the first lumbar vertebral body showed an age-dependent decline in SHAM rats. Relative to SHAM controls, ORX rats had significantly reduced cancellous BAr after 2 weeks post-ORX in the tibia and after 2 months post-ORX in the vertebral body. Thereafter, vertebral and tibial cancellous BAr continued to decline in ORX animals throughout the study. Osteoclast number (NOc), osteoblast surface, bone formation rate (BFR), and activation frequency were increased in ORX animals from 1 month postsurgery until the end of the trial. Moreover, in close temporal association with the histomorphometric findings, serum osteocalcin and urinary excretion of collagen cross-links and calcium were elevated in ORX rats. In a stepwise model of multiple regression analysis using estradiol and free and total testosterone as independent variables, estradiol was the only significant predictor of histomorphometric indices of bone formation and bone resorption in SHAM and ORX rats. These data show that androgen deficiency induces substantial loss of cancellous bone in the axial and appendicular skeleton of aged male rats and that this osteopenia is associated with a sustained increase in bone turnover. Thus, the skeletal effects of androgen withdrawal in aged male rats appear to resemble those induced by estrogen withdrawal in female rats. Furthermore, our study suggests that estradiol may act as a physiological suppressor of bone remodeling in aged male rats.

Aging↗

Production of pheromones by artificially fed males of the tick Amblyomma maculatum (Acari: Ixodidae).

Aggregation-attachment pheromones are produced only by male ticks of the genus Amblyomma that have imbibed blood for at least 8 d from their mammalian hosts. This report demonstrates that production and release of aggregation-attachment pheromones by Amblyomma maculatum (Koch) males can be induced in vitro by using nonblood media, artificially introduced through capillary tubes, into the male ticks. The presence of these pheromones is demonstrated by using both biological observations on bovine hosts and in vitro experimentation with petri dishes. The attraction of unfed female ticks to the artificially fed males (using the petri dish method) was significantly higher (P < 0.001) than the attraction of unfed females to unfed males. Similarly, attraction and attachment were recorded on bovine hosts. Only 62.8 +/- 17.5% of the females released attached to the bovine host. Of these, 61.9 +/- 19.37% attached around artificially fed males that were placed on the bovine 24 h earlier. This percentage did not differ significantly from the 81.4 +/- 7.1% of the total that attached around males that fed naturally for 8 d. In comparison, only 33.3 +/- 21.9% of the total number of females placed on the host did so after being fed 1 d (control group). The possibility of using capillary feeding as a new tool for investigating the physiology and reproductive behavior of blood-sucking arthropods is discussed.

Animals↗

Past occupational exposure to asbestos among men in France.

OBJECTIVES: This study aimed at reconstructing changes in the frequency and levels of occupational asbestos exposure in France over the past century. METHODS: Work histories were collected during 11 population-based case-referent studies recently carried out in France, and an asbestos-specific job-exposure matrix including 10 625 jobs was used to estimate indices of past occupational asbestos exposure. The results were estimated from a sample of 4287 subjects, bootstrapped 200 times. RESULTS: The distribution of socioeconomic categories within the sample was compared with that of the general population in 1954, 1962, 1968, 1975, and 1982. The proportion of blue-collar workers was similar. The highest proportion of exposed subjects was found between 1950 and 1980. Around 10% of each 10-year age class was exposed to asbestos. For those born in 1930-1939, 15.2% was exposed between the ages of 20 and 29 years. For each age class born in 190-1939, the proportion exposed at least once by 60 years of age ranged from 18.2% to 24.5 % and, of those exposed, the cumulative duration of exposure ranged from 11.3 to 15.4 years by the age of 60 years. A population exposure index showed that the heaviest exposure occurred between 1960 and 1970 and that the age classes born between 1920 and 1929 were the most heavily exposed. Time trends showed that the mean value of this index for the men aged 20-59 years reached a peak in the 1960s and then decreased. CONCLUSIONS: This study presents data of reasonable validity about occupational asbestos exposure in France and its trends over the past century; the data are being used to forecast the development of male mortality from mesothelioma in France.

Adolescent↗

Autistic savants. [correction of artistic].

OBJECTIVE: The objectives of this study were to examine common patterns in the lives and artwork of five artistic savants previously described and to report on the clinical, neuropsychological, and neuroimaging findings from one newly diagnosed artistic savant. BACKGROUND: The artistic savant syndrome has been recognized for centuries, although its neuroanatomic basis remains a mystery. METHODS: The cardinal features, strengths, and weaknesses of the work of these six savants were analyzed and compared with those of children with autism in whom artistic talent was absent. An anatomic substrate for these behaviors was considered in the context of newly emerging theories related to paradoxical functional facilitation, visual thinking, and multiple intelligences. RESULTS: The artists had features of "pervasive developmental disorder," including impairment in social interaction and communication as well as restricted repetitive and stereotyped patterns of behavior, interest, and activities. All six demonstrated a strong preference for a single art medium and showed a restricted variation in artistic themes. None understood art theory. Some autistic features contributed to their success, including attention to visual detail, a tendency toward ritualistic compulsive repetition, the ability to focus on one topic at the expense of other interests, and intact memory and visuospatial skills. CONCLUSIONS: The artistic savant syndrome remains rare and mysterious in origin. Savants exhibit extraordinary visual talents along with profound linguistic and social impairment. The intense focus on and ability to remember visual detail contributes to the artistic product of the savant. The anatomic substrate for the savant syndrome may involve loss of function in the left temporal lobe with enhanced function of the posterior neocortex.

Adolescent↗

Surgical treatment of metastatic pulmonary soft-tissue sarcoma.

The lung is the most frequent site of metastasis from soft-tissue sarcomas. Due to the relative resistance of sarcoma to either chemotherapy or radiotherapy, compared to other solid tumors, surgical management of pulmonary metastases has been a pivotal therapy in this disease. With decades of experience in numerous centers, criteria for patient selection have been ascertained and documented. We review the current literature on the use of pulmonary metastasectomy in patients with soft-tissue sarcoma, as well as survival data after such treatment. Osteogenic sarcoma is not included in this discussion.

Biomarkers, Tumor↗

[Psychometric properties of the French version of the Effort-Reward Imbalance model].

BACKGROUND: Two main models are currently used to evaluate psychosocial factors at work: the Job Strain model developed by Karasek and the Effort-Reward Imbalance model. A French version of the first model has been validated for the dimensions of psychological demands and decision latitude. As regards the second one evaluating three dimensions (extrinsic effort, reward, and intrinsic effort), there are several versions in different languages, but until recently there was no validated French version. The objective of this study was to explore the psychometric properties of the French version of the Effort-Reward Imbalance model in terms of internal consistency, factorial validity, and discriminant validity. METHODS: The present study was based on the GAZEL cohort and included the 10 174 subjects who were working at the French national electric and gas company (EDF-GDF) and answered the questionnaire in 1998. A French version of Effort-Reward Imbalance was included in this questionnaire. This version was obtained by a standard forward/backward translation procedure. RESULTS: Internal consistency was satisfactory for the three scales of extrinsic effort, reward, and intrinsic effort: Cronbach's Alpha coefficients higher than 0.7 were observed. A one-factor solution was retained for the factor analysis of the scale of extrinsic effort. A three-factor solution was retained for the factor analysis of reward, and these dimensions were interpreted as the factor analysis of intrinsic effort did not support the expected four-dimension structure. The analysis of discriminant validity displayed significant associations between measures of Effort-Reward Imbalance and the variables of sex, age, education level, and occupational grade. CONCLUSION: This study is the first one supporting satisfactory psychometric properties of the French version of the Effort-Reward Imbalance model. However, the factorial validity of intrinsic effort could be questioned. Furthermore, as most previous studies were based on male samples working in specific occupations, the present one is also one of the first to show strong associations between measures of this model and social class variables in a population of men and women employed in various occupations.

Adult↗

Lung cancer. Diagnostic tools.

Early diagnosis of lung cancer represents the best method for improving survival rates. The diagnostic aids available have improved exponentially on old and new techniques over the past 20 years. The greatest impact has been in computed tomography and positron emission tomography scanning imaging techniques. In the future, these techniques will improve, and others such as monoclonal antibody scans and antisense imaging techniques will certainly further enhance the physician's ability to diagnose earlier, and thereby, treat earlier.

Biopsy, Needle↗

The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.

During apoptosis, an important pathway leading to caspase activation involves the release of cytochrome c from the intermembrane space of mitochondria. Using a cell-free system based on Xenopus egg extracts, we examined changes in the outer mitochondrial membrane accompanying cytochrome c efflux. The pro-apoptotic proteins, Bid and Bax, as well as factors present in Xenopus egg cytosol, each induced cytochrome c release when incubated with isolated mitochondria. These factors caused a permeabilization of the outer membrane that allowed the corelease of multiple intermembrane space proteins: cytochrome c, adenylate kinase and sulfite oxidase. The efflux process is thus nonspecific. None of the cytochrome c-releasing factors caused detectable mitochondrial swelling, arguing that matrix swelling is not required for outer membrane permeability in this system. Bid and Bax caused complete release of cytochrome c but only a limited permeabilization of the outer membrane, as measured by the accessibility of inner membrane-associated respiratory complexes III and IV to exogenously added cytochrome c. However, outer membrane permeability was strikingly increased by a macromolecular cytosolic factor, termed PEF (permeability enhancing factor). We hypothesize that PEF activity could help determine whether cells can recover from mitochondrial cytochrome c release.

Adenylate Kinase↗

Energetics and topology of CzcA, a cation/proton antiporter of the resistance-nodulation-cell division protein family.

The membrane-bound CzcA protein, a member of the resistance-nodulation-cell division (RND) permease superfamily, is part of the CzcCB(2)A complex that mediates heavy metal resistance in Ralstonia sp. CH34 by an active cation efflux mechanism driven by cation/proton antiport. CzcA was purified to homogeneity after expression in Escherichia coli, reconstituted into proteoliposomes, and the kinetics of heavy metal transport by CzcA was determined. CzcA is composed of 12 transmembrane alpha-helices and two large periplasmic domains. Two conserved aspartate and a glutamate residue in one of these transmembrane spans are essential for heavy metal resistance and proton/cation antiport but not for facilitated diffusion of cations. Generalization of the resulting model for the function of CzcA as a two-channel pump might help to explain the functions of other RND proteins in bacteria and eukaryotes.

Amino Acid Sequence↗

The tail domain of lamin Dm0 binds histones H2A and H2B.

In multicellular organisms, the higher order organization of chromatin during interphase and the reassembly of the nuclear envelope during mitosis are thought to involve an interaction between the nuclear lamina and chromatin. The nuclear distribution of lamins and of peripheral chromatin is highly correlated in vivo, and lamins bind specifically to chromatin in vitro. Deletion mutants of Drosophila lamin Dm0 were expressed to map regions of the protein that are required for its binding to chromosomes. The binding activity requires two regions in the lamin Dm0 tail domain. The apparent Kd of binding of the lamin Dm0 tail domain was found to be approximately 1 microM. Chromatin subfractions were examined to search for possible target molecules for the binding of lamin Dm0. Isolated polynucleosomes, nucleosomes, histone octamer, histone H2A/H2B dimer, and histones H2A or H2B displaced the binding of lamin Dm0 tail to chromosomes. This displacement was specific, because polyamines or proteins such as histones H1, H3, or H4 did not displace the binding of the lamin Dm0 tail to chromosomes. In addition, DNA sequences, including M/SARs, did not interfere with the binding of lamin Dm0 tail domain to chromosomes. Taken together, these results suggest that the interaction between the tail domain of lamin Dm0 and histones H2A and H2B may mediate the attachment of the nuclear lamina to chromosomes in vivo.

Amino Acid Sequence↗

Temporal differences in the appearance of NEP-B78 and an LBR-like protein during Xenopus nuclear envelope reassembly reflect the ordered recruitment of functionally discrete vesicle types.

In this work, we have used novel mAbs against two proteins of the endoplasmic reticulum and outer nuclear membrane, termed NEP-B78 and p65, in addition to a polyclonal antibody against the inner nuclear membrane protein LBR (lamin B receptor), to study the order and dynamics of NE reassembly in the Xenopus cell-free system. Using these reagents, we demonstrate differences in the timing of recruitment of their cognate membrane proteins to the surface of decondensing chromatin in both the cell-free system and XLK-2 cells. We show unequivocally that, in the cell-free system, two functionally and biochemically distinct vesicle types are necessary for NE assembly. We find that the process of distinct vesicle recruitment to chromatin is an ordered one and that NEP-B78 defines a vesicle population involved in the earliest events of reassembly in this system. Finally, we present evidence that NEP-B78 may be required for the targeting of these vesicles to the surface of decondensing chromatin in this system. The results have important implications for the understanding of the mechanisms of nuclear envelope disassembly and reassembly during mitosis and for the development of systems to identify novel molecules that control these processes.

Animals↗

Factors responsible for pulp cell cytotoxicity induced by resin-modified glass ionomer cements.

Resin-modified glass ionomer cements (RM-GICs) are the last generation of GICs commonly used in restorative dentistry. They contain various resins that improve their mechanical properties. These modifications, however, may also affect their biocompatibility. We compared the cytotoxicity of seven biomaterials (five RM-GICs, one metal-reinforced GIC (M-GIC), and a zinc-oxyphosphate cement) using an assay of pulp cell viability in vitro (MTT assay). The most toxic materials appeared to be the M-GIC Hi-Dense and the RM-GIC Vitremer. The less toxic ones appeared to be the RM-GICs Compoglass and Photac-Fil. Attempts made to identify the factors responsible for their cytotoxicity indicated that in vitro cytotoxicity did not seem to be caused by any change in pH of the biomaterial eluates. Adsorption of biomaterial eluates on dentin powder significantly reduced the cytotoxicity of all biomaterials. The concentration of F-, Sr2+, and Al3+ (major ionic elements present in GICs) in the eluate of six glass ionomer containing biomaterials was too low to be cytotoxic. However, Cu2+ and Ag+ (present in alloys of M-GIC) were present in toxic concentrations in Hi-Dense eluates. Unpolymerized monomers leached from resins were identified by Fourier transform IR spectroscopy in biomaterial eluates. The monomers hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA), and poly(acrylic) acid were identified in eluates of Vitremer, Compoglass, and Hi-Dense, respectively. After ethanol elution of HEMA and TEGDMA from Vitremer and Compoglass, respectively, the cytotoxicity of these two RM-GICs was drastically reduced. Our results suggest that the principal compounds responsible for cytotoxicity are unpolymerized resin monomers in the two RM-GICs and Cu2+ and Ag+ in the M-GIC.

Adolescent↗

[3H]choline uptake and turnover into membrane and extracellular matrix phospholipids, visualized by radioautography in rat incisor dentin and enamel.

In order to study the uptake and fate of [3H]choline into cellular and extracellular phospholipids in the forming part of mandibular rat incisors, radioautography was carried out after treatment with the iodoplatinate reaction which retains phospholipids. Thirty minutes and 1 hour after the intravenous injection of the radiolabeled precursor, grain density in secretory odontoblasts and ameloblasts was not significantly above background labeling whereas dentin was actually labeled. Therefore, at this early period, odontoblasts cannot be responsible for the secretion of phospholipids incorporated into dentin, and intercellular diffusion of components originating from blood could explain this early dentin labeling. After 2 hours, odontoblasts and ameloblasts were labeled. In cells, grain density reached a maximum at 4 hours, reduced at 24 hours, and strongly decreased at 4 days. In predentin and enamel, grain density peaked at 24 hours and diminished at 4 days. However, in the forming enamel 4 days after the injection, labeling was twice as high as in any other compartment. Altogether, the results highlighted two distinct pathways for phospholipids in dental mineralized dental tissues: a first one shows evidence of early incorporation of [3H]choline into dentin resulting from intercellular diffusion independently from odontoblasts secretion, whereas inside the forming enamel, higher labeling and longer retention of choline-containing membrane components were detected between 4 hours and 4 days. This suggests an accumulation of membranes that are not subjected to rapid turnover in contrast with other dental compartments.

Ameloblasts↗