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Biomedical subjects

M Goldberg

Publications and source records attributed to M Goldberg.

At least 163 records · Page 9Linked to original sources

The effect of the OSHA lead exposure in construction standard on blood lead levels among iron workers employed in bridge rehabilitation.

Over 50,000 workers are at risk of occupational exposure to lead in the course of renovating the nation's deteriorating infrastructure. In mid-1993, to control exposure to lead in the construction setting OSHA promulgated a Lead in Construction Standard. In this study, we assessed the effect of the mandated changes in exposure conditions which followed the introduction of this new standard. We analyzed changes in baseline and maximum blood lead concentrations and in maximum increments in blood lead levels before and after introduction of the standard among iron workers employed in the renovation of a large, lead-painted, steel bridge in New York City. Results indicated that baseline and maximum blood lead levels fell significantly after the implementation of the provisions of the standard, as did maximum increments in blood lead concentrations. Seventy-six percent of the workers maintained blood lead concentrations below 20 micrograms/dl after the OSHA standard, as compared with 66% prior to its implementation. Increments of 20 micrograms/dl or more occurred considerably more frequently before introduction of the standard (13% before vs. 4% after; p = 0.01). Evidence of decreased exposure to lead was observed among iron workers who were present both before and after the introduction of the OSHA standard, as well as among iron workers newly hired after the OSHA provisions were put in place. These findings document the effectiveness of the OSHA construction lead standard in controlling exposure to lead in this complex and variable environment. The data indicate the utility of blood lead determinations in assessing the outcome of industrial hygiene interventions to reduce exposures to lead in the construction setting.

Adult↗

A task-based approach to assessing lead exposure among iron workers engaged in bridge rehabilitation.

The assessment of worker exposures to airborne contaminants in the dynamic environment present at most construction sites poses considerable challenges to the industrial hygienist. In this study, we applied a task-based approach to the assessment of lead exposure among structural steel iron workers engaged in a large, complex bridge rehabilitation project. We evaluated the usefulness of task-based exposure data for the development of worker protection programs. Task-specific and multitask samples were collected, and operation-specific and 8-hr time-weighted averages were calculated. The task-specific data showed significant differences in exposure levels among different tasks. Arithmetic mean exposures varied from 1,357 micrograms/m3 lead for torch cutting and 989 micrograms/m3 for scaling to 31 micrograms/m3 for reaming and 4 micrograms/m3 for drilling. Our task-specific data were compared with the task-based exposure levels presented by OSHA in its Lead Exposure in Construction-Interim Final Rule (29 CFR 1926). There was good general agreement between our results and OSHA's reported data. Task-based data were very useful in exposure assessment and much more precise than full-shift and operation-based measurements in guiding strategies for worker protection. These findings suggest that task-based data should routinely be collected in evaluating exposure to lead and perhaps other toxic substances in construction work.

Air Pollutants, Occupational↗

In vitro culture of human dental pulp cells: some aspects of cells emerging early from the explant.

Cells emerging from a dental pulp explant were studied in order to elucidate the origin of precursor cells implicated in the formation of reparative dentin in vivo. Such cells observed at the very early stage of culture (days 5-10) were different from fibroblast-like cells obtained after one subculture. These early cells were round or elongated, with thin spinous processes, highly mobile, and contained numerous lipid vesicles. Incorporation of 1-[14C]palmitic acid did not show an increased incorporation of radiolabeled total lipids or triglycerides into these early cells compared to cells after four subcultures or control skin fibroblasts, suggesting that the lipids in vesicles were not synthesized by the cells. Since these cells also show a high level of fluid phase uptake via macropinocytosis, it is suggested that these lipids originate from macropinocytosis. Between days 10 and 20, these cells spontaneously start conversion into cells that have a fibroblast-like morphology, are less mobile, and lack lipid vesicles. Their morphology, movement, and macropinocytosis suggest that these cells, which migrate from the pulp explants, are mesenchymal cells related to mononuclear phagocytes/histiocytes.

Adolescent↗

Morphometric analysis of collagen and elastic fibers in normal skin and gingiva in relation to age.

The morphometric parameters of the human gingival elastic fiber network were determined by image analysis and compared with human skin elastic fibers in relation to age. Similarly, collagen fibers were also investigated in both tissues. In this study, 47 healthy patients, 10-75 years old were studied for gingiva and another 50 patients in the same age range were included for skin biopsies. Three groups were compared: group 1 from the age of 10-24 years, group 2 from 25 to 49 years, and group 3 from 50 to 75 years. The diameters of the oxytalan fibers were invariable in both tissues, whatever the age considered. On the other hand, the diameters of elastic fibers increased regularly with age in the gingiva (P < 0.01) and in the skin (P < 0.01) between each age group. The area fraction occupied by the oxytalan fibers decreased significantly in both tissues (P < 0.01) for the skin and (P < 0.001) for the gingiva. The area fraction occupied by the gingival elastic fibers remained constant with age while the skin elastic fibers increased significantly with age between groups 2 and 1 (P < 0.01) and between groups 3 and 2 (P < 0.001). In the mid-dermis and in the mid-gingiva, the diameters of the collagen fibers increased strongly with age, between groups 2 and 1 (P < 0.01) and between groups 3 and 2 (P < 0.001). The area fraction occupied by the collagen bundles increased regularly with age in the mid-gingival (P < 0.05 between each age group), while a significant decrease was observed in the mid-dermis from the age of 50-75 years (P < 0.05). The results obtained contribute to a better understanding of some modifications which dermis and gingiva undergo with aging and provide data to perfect diagnosis and therapy in odontology and dermatology.

Adolescent↗

Pleural cytologies in lung cancer without pleural effusions.

BACKGROUND: Malignant pleural effusions significantly increase the stage of lung cancer with attendant worsening of prognosis. There is a paucity of literature evaluating malignant pleural lavage cytology in patients without pleural effusions. We propose to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for lung cancer and to identify any predictive risk factors for positive cytology. METHODS: Seventy-eight patients underwent curative resection for lung cancer. Lavage was performed before lung manipulation and after resection and cytologically evaluated. RESULTS: Twelve pneumonectomies, 64 lobectomies, and 2 wedge resections were performed on 40 men and 38 women with an average age of 65.7 years. Fourteen percent had positive lavage cytology before lung resection with an 11% (6 of 53) incidence in stage I. A significant correlation to adenocarcinoma compared with squamous cell was found (p = 0.03) but not to stage, T or N status, grade, pleural invasion, or preoperative transthoracic needle biopsy. CONCLUSIONS: The incidence of positive pleural cytology in otherwise stage I patients is disconcertingly high. Positive cytology may be a prognosticator of a more aggressive tumor biology.

Adult↗

Coordinate induction of tetrahydrobiopterin synthesis and nitric oxide synthase activity in chicken macrophages: upregulation of GTP-cyclohydrolase I activity.

Biosynthesis of nitric oxide (NO) and tetrahydrobiopterin (BH4) was investigated during cytokine-mediated activation of chicken macrophages. Monocyte derived macrophages and HD11 cells, a chicken macrophage cell line, constitutively synthesize BH4. Treatment of these cells with chicken macrophage activation factor (ChMAF) causes up to 10-fold increases of intracellular BH4 and of nitrite concentrations in the cell culture supernatant. Elevated BH4 levels correlate with an increase in GTP-cyclohydrolase I (GTP-CH) activity. Kinetic studies show a joint upregulation of GTP-CH activity and NO synthase activity first detectable 4 hr after stimulation. A corresponding increase in the mRNA for GTP-CH was detected by Northern blot analysis with a chicken GTP-CH specific cDNA probe. These results demonstrate that cytokine-induced BH4 synthesis by chicken macrophages is at least partially regulated through increased GTP-CH gene expression. The functional relevance of BH4 formation for NO production is shown by experiments using 2,4-diamino-6-hydroxypyrimidine (DAHP) as a specific inhibitor of GTP-CH. Monocyte derived macrophages stimulated in the presence of DAHP show a significant decrease in NO synthesis. The effect of DAHP was reversed by adding sepiapterin, which allows synthesis of BH4 through a salvage pathway.

Animals↗

Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni.

To investigate the role of tegumental glycoprotein Sm25 in protective immunity against schistosomiasis, codons 43-182 of its gene (GP22) were amplified by PCR and cloned in the pET 15b bacterial expression system. Recombinant protein r140 was inducibly expressed in the presence of rifampicin and purified by Ni-affinity chromatography. In different vaccination trials, Balb/c mice and Fischer rats repeatedly immunized with r140 in combination with one of several adjuvants (alum, cholera toxin or complexed into proteosomes) produced high titre anti-r140 responses. These antibodies detected an N-glycanase sensitive. 25 kDa antigen in a detergent solubilized worm fraction using Western immunoblotting. The choice of adjuvant affected the isotype distribution of the specific anti-r140 antibodies. Despite the presence of high antibody titres and isotypes which have been shown to correlate with protective immunity, protection against subsequent cercarial challenge was not observed. In addition, no appreciable effects on worm sex ratios or liver egg yields were detected in mice. Studies involving biotin labelling of membrane proteins in live worms showed that the majority of anti-r140 reactive molecules present in adult schistosomes are biotinylated after permeabilization of the parasite surface. Several possibilities to account for the lack of protective immunity are analysed.

Adjuvants, Immunologic↗

Nuclear membrane vesicle targeting to chromatin in a Drosophila embryo cell-free system.

A Drosophila cell-free system was used to characterize proteins that are required for targeting vesicles to chromatin and for fusion of vesicles to form nuclear envelopes. Treatment of vesicles with 1 M NaCl abolished their ability to bind to chromatin. Binding of salt-treated vesicles to chromatin could be restored by adding the dialyzed salt extract. Lamin Dm is one of the peripheral proteins whose activity was required, since supplying interphase lamin isoforms Dm1, and Dm2 to the assembly extract restored binding. As opposed to the findings in Xenopus, okadaic acid had no effect on vesicle binding. Trypsin digestion of the salt-stripped vesicles eliminated their association with chromatin even in the presence of the dialyzed salt extract. One vesicles attached to chromatin surface, fusion events took place were found to be sensitive to guanosine 5'-[gamma-thio]triphosphate (GTP gamma S). These chromatin-attached vesicles contained lamin Dm and otefin but not gp210. Thus, these results show that in Drosophila there are two populations of nuclear vesicles. The population that interacts first with chromatin contains lamin and otefin and requires both peripheral and integral membrane proteins, whereas fusion of vesicles requires GTPase activity.

Animals↗

Evidence for attachment pheromones in the Cayenne tick (Acari:Ixodidae).

Evidence is presented for the existence of male-produced attachment pheromones in the tick Amblyomma cajennense (F). Unfed males and females attached significantly faster to shaved sides on bovine hosts where preattached males were present than did adult ticks released in control areas. Attached ticks did not form clusters around the preattached males as described for other species of Amblyomma. They attached in areas under bags where they had been released, but were not necessarily close to the feeding males. Males apparently required at least 4 d of feeding before producing the pheromones. Males that fed for < 3 d failed to induce attachment. A significant increase in attachment of newly introduced males and females was observed only on day 4 after the feeding of the preattached male started. This response increased on days 5 and 6 after feeding had commenced. An evolutionary trend in the production of tick pheromones was suggested.

Animals↗

Cyclosporin A-induced alterations of dentinogenesis in rat molars.

Cyclosporin A (CsA), a widely used immunosuppressive drug, induces gingival overgrowth and modifications of bone remodelling. The scope of this study was to investigate the possible effect of CsA on dentin. Thirty mg/kg/day of CsA were administered orally to male Sprague-Dawley rats for nineteen weeks. The same number of control rats received oil-based vehicle solution. Rats were anesthetized, and tissues were fixed by an intracardiac perfusion of fixative solution. Mandibles were dissected, demineralized, and processed for Epon embedding. Semi-thin sections of the first molars revealed alterations at the secondary dentin-pulp interface in four out of six experimental animals. The changes consisted of the formation of: 1) osteodentin spurs, in which the volume and interface with the secondary dentin varied from about 25,000 to 75,000 microns 3 and from 1400 to 3530 microns 2, respectively; 2) abnormally shaped and irregularly spaced incremental lines; and 3) numerous globular formations embedded in dentin or free in the pulp. These results indicate that CsA induces abnormal mineralized matrix formation in dentin and in the peripheral part of the pulp in rat molars.

Administration, Oral↗

Localization and posttranslational modifications of otefin, a protein required for vesicle attachment to chromatin, during Drosophila melanogaster development.

Otefin is a peripheral protein of the inner nuclear membrane in Drosophila melanogaster. Here we show that during nuclear assembly in vitro, it is required for the attachment of membrane vesicles to chromatin. With the exception of sperm cells, otefin colocalizes with lamin Dm0 derivatives in situ and presumably in vivo and is present in all somatic cells examined during the different stages of Drosophila development. In the egg chamber, otefin accumulates in the cytoplasm, in the nuclear periphery, and within the nucleoplasm of the oocyte, in a pattern similar to that of lamin Dm0 derivatives. There is a relatively large nonnuclear pool of otefin present from stages 6 to 7 of egg chamber maturation through 6 to 8 h of embryonic development at 25 degrees C. In this pool, otefin is peripherally associated with a fraction containing the membrane vesicles. This association is biochemically different from the association of otefin with the nuclear envelope. Otefin is a phosphoprotein in vivo and is a substrate for in vitro phosphorylation by cdc2 kinase and cyclic AMP-dependent protein kinase. A major site for cdc2 kinase phosphorylation in vitro was mapped to serine 36 of otefin. Together, our data suggest an essential role for otefin in the assembly of the Drosophila nuclear envelope.

Animals↗

Management of carcinoma of the superior pulmonary sulcus.

Tumors of the superior pulmonary sulcus (Pancoast tumors) are bronchogenic carcinomas that occur at the thoracic inlet and typically involve, by direct extension, the lower trunks of the brachial plexus, the intercostal nerves, the stellate ganglion, and adjacent ribs and vertebrae. These tumors are rare, comprising 5% of all lung cancers. Treatment of Pancoast tumors has traditionally consisted of preoperative radiation to a dose of 3,000 to 4,500 cGy followed by surgical resection. Overall 5-year survival rates range from 30% to 50%. Even if treatment achieves local disease control, distant failure (brain or bone) is common. Recent treatment efforts have focused on the use of induction chemoradiation followed by surgery and further chemotherapy. This combined-modality approach may become the new treatment paradigm for Pancoast tumors.

Biopsy, Needle↗

Combined-modality therapy for esophageal cancer: phase I trial of escalating doses of paclitaxel in combination with cisplatin, 5-fluorouracil, and high-dose radiation before esophagectomy.

Several recent reports support administering preoperative chemotherapy and radiotherapy to improve the outcome of patients with resectable esophageal malignancies. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), 5-fluorouracil (5-FU), and cisplatin are known radiosensitizers, and paclitaxel has demonstrated single-agent activity in patients with metastatic esophageal cancer. This study sought to define the maximum tolerated dose of paclitaxel given with 5-FU, cisplatin, and 60 Gy radiotherapy before esophagectomy to patients with potentially resectable lesions. Seventeen patients so treated underwent esophagectomy. Three patients with metastatic disease, treated to obtain more information about the toxicity of the combined-modality regimen, did not undergo surgery. Over 6 weeks, 60 Gy radiation was administered in 2-Gy fractions. During radiation treatment, continuous intravenous infusions of 5-FU 225 mg/m2/d were administered, with paclitaxel given weekly as a 1-hour intravenous infusion immediately preceding a 1-hour cisplatin infusion. Surgery was performed 4 to 6 weeks after the completion of radiotherapy. The 27 patients, one of whom was a woman, had a median age of 58 years and an Eastern Cooperative Oncology Group performance status of 0 (10 patients) or 1. Three patients had a squamous cell histology, while 22 had adenocarcinoma; two had other histologies. The paclitaxel dose levels were 25 mg/m2 in four patients, 40 mg/m2 in five patients, 60 mg/m2 in nine patients, and paclitaxel 50 mg/m2 with 5-FU reduced to 200 mg/m2 in nine patients. The latter proved to be the maximum tolerated dose combination, with cisplatin held constant at 25 mg/m2. This level represents weekly dose intensities of 9.6 Gy radiation, 48 mg/m2 paclitaxel, 24 mg/m2 cisplatin, and 192 mg/m2 5-FU. Diarrhea in four patients, mucositis and dehydration in seven, electrolyte wasting in two, gram-positive catheter-related infection in three, and neuropathy in one proved dose limiting. Hematologic toxicity was relatively mild, with three episodes of nonneutropenic bacteremia, one of which was fatal. Postoperative chemotherapy consisting of four cycles of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75 mg/m2 over 1 hour every 3 weeks was planned but rarely feasible due to postoperative morbidity and poor tolerability of postoperative chemotherapy. Therefore, the use of two induction cycles of this regimen given before the combined-modality study regimen is currently being investigated. Of 17 patients whose surgical specimens were assessed pathologically, three had complete remissions and 14 had partial remissions, five of which were characterized as very good, showing only microscopic foci and marked radiation effects. The median follow-up of the 17 patients who underwent surgery is 50 weeks (range, 5 to 111 weeks). Three relapses occurred at 26, 33, and 43 weeks. We conclude that this is an intense combined-modality preoperative regimen for patients with esophageal cancer. Determining the efficacy of this regimen will require further follow-up and the performance of phase II trials.

Adenocarcinoma↗

[Comparative investigation of the efficacy of two nucleocapsid analogs in FIV infected cats].

Antiviral activity of the acyclic nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) against feline immunodeficiency virus (FIV) was investigated in field cats. The study was designed as a placebo-controlled double-blind study enrolling 27 FIV infected cats. Nine cats received PMEA at a dosage of 10 mg/kg body weight, nine cats received FPMPA at a dosage of 25 mg/kg body weight. A variety of parameters were established to evaluate the therapeutic efficacy of the compounds. The improvement was monitored by different aspects: clinical status, index of Karnofsky modified for the cat, laboratory parameters, immunological parameters, surrogate markers, and a virological parameter. Concerning the clinical and immunological parameters cats of both treatment groups disclosed a relevant improvement. Efficacy of antiviral treatment was a little bit higher in the cats treated with PMEA than in the animals injected with FPMPA. However, side effects were also more prominent in the PMEA treated group.

Adenine↗

Exposure to 50-Hz electric field and incidence of leukemia, brain tumors, and other cancers among French electric utility workers.

Recent studies on the association between exposure to 50- to 60-Hz fields and cancer carried out among electric utility workers have focused mainly on the magnetic field component of exposure. The authors have investigated tumor risks specifically associated with electric fields, as this exposure is distinct from magnetic fields. The study design is a case-control study nested within a cohort of 170,000 workers employed at Electricité de France-Gaz de France (EDF) between 1978 and 1989. All incident cases of cancer and benign tumor of the brain diagnosed in 1978-1989 among workers before the age of retirement were included. Four randomly selected controls were individually matched to each case by year of birth. The exposure to electric fields was assessed from measurements collected in 850 EDF workers for a full work week. Arithmetic and geometric mean exposures were included in a job-exposure matrix to determine the cumulative exposure of the cases and the controls. Exposures to potentially carcinogenic chemicals found at the workplace were also evaluated through expert judgment. The analysis by site of tumor did not show any increased risk for leukemia (72 cases). An odds ratio of 3.08 (95% confidence interval 1.08-8.74) was observed for all brain tumors (69 cases) for exposure above the 90th percentile (> or = 387 V/m-year), and there was some indication of a dose-response relation, although the risk did not increase monotonically with exposure. No confounding from magnetic fields or from other potentially carcinogenic hazards was apparent. The observed association was somewhat stronger after allowing a 5-year latency period before diagnosis (odds ratio = 3.69, 95% confidence interval 1.10-12.43) for exposure above the 90th percentile. However, the risk of brain tumor could not be linked to a specific type of tumor. An unexpected association was also observed for colon cancer, using geometric indexes of exposure, but no other association was seen for any other type of cancer. Our study indicates that electric fields may have a specific effect on the risk of brain tumor, and that this should be taken into account in future analyses on the carcinogenic effects of 50- to 60-Hz fields.

Brain Neoplasms↗