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Biomedical subjects

E Rosenberg

Publications and source records attributed to E Rosenberg.

At least 19 recordsLinked to original sources

Cholesterol screening of children at high risk: behavioural and psychological effects.

OBJECTIVE: To assess the behavioural and psychosocial effects of screening asymptomatic children at high risk for hyperlipidemia. DESIGN: Observational study involving prospective longitudinal and cross-sectional portions. SETTING: Two tertiary care pediatric lipid clinics in Montreal. SUBJECTS: Longitudinal portion: all children aged 4 to 17 years who presented for screening at the lipid clinics between April 1990 and June 1991. Of the 56 eligible children 52 (93%) (and their mothers) agreed to participate, 34 with hyperlipidemia (case subjects) and 18 without hyperlipidemia (control subjects). Thirty-five children (67%) completed 3 assessments over 12 months. Cross-sectional portion: all children aged 4 to 17 years in whom hyperlipidemia had been diagnosed 2 to 5 years earlier at one of the lipid clinics. Of the 58 eligible children 48 (83%) (and their mothers) participated. OUTCOME MEASURES: For children, mean scores on the Child Behavior Checklist (Behavior Problems subscale) (CBCL), the Children's Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC); for mothers, mean scores on the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). RESULTS: In the longitudinal portion of the study, there was no significant difference between the case and control subjects in the mean CDI or STAIC scores at 1 or 12 months. At 1 month after diagnosis the case subjects in the longitudinal portion had a significantly higher mean CBCL score than the children in the cross-sectional component (p = 0.01). With the control group as the reference group, the adjusted odds ratios for a high CBCL score (greater than 62) for the case subjects were 15.5 (95% confidence interval [CI] 2.4 to 99.8) at 1 month and 15.8 (95% CI 1.1 to 223.4) at 12 months. The corresponding values for the children in the cross-sectional component were 1.3 (95% CI 0.3 to 6.2) and 5.0 (95% CI 0.5 to 50.9). CONCLUSIONS: The observed behavioural problems in children with a recent diagnosis of hyperlipidemia were independent of other risk factors, such as age and sex of child and mother's age and BDI score. Our results suggest that identification of hyperlipidemia in children may have harmful psychological effects in the families involved. This evidence strengthens arguments for the exclusion of cholesterol measurement from the periodic health examination of children at moderately high risk.

Adolescent

Bioemulsans: microbial polymeric emulsifiers.

Bioemulsans are amphipathic proteins and/or polysaccharides that stabilize oil-in-water emulsions. Bioemulsans are produced by a wide diversity of microorganisms and have potential applications in the food, paper, paint, bioremediation, agriculture, detergent and cosmetics industries. The production of the RAG-1 emulsan has been studied in batch-fed fermentors via self-cycling fermentation and with immobilized cells using a Celite support matrix. Bioemulsans have several advantages over lower molecular weight emulsifiers presently used in industry. The last few years have seen a number of new bioemulsans described with commercial applications.

Azotobacter

A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common but little-studied disorder in the elderly that is infrequently recognized by physicians. Its prevalence in adults over 40 years of age is estimated at 3.8% for men and 2.6% for women. The present case-control study evaluated the history of pain and stiffness, radicular pain and enthesitis, physical findings on the musculoskeletal examination, and level of physical and psychologic disability in 130 persons: 56 patients with DISH, 43 control patients with spondylosis of the lumbar spine, and 31 healthy control patients. DISH patients were more likely to report a past history of upper extremity pain, medial epicondylitis of the elbow, enthesitis of the patella or heel, or dysphagia than spondylosis patients. They had more extremity and spinal stiffness and pain than healthy controls. DISH patients weighed more at a young age and their body mass index was greater at the time of the clinical evaluation than either spondylosis or healthy control patients. On musculoskeletal examination, DISH patients had a greater reduction in neck rotation and thoracic movements than either spondylosis patients or healthy controls, and had a greater reduction in lumbar movement than healthy controls. DISH patients had similar levels of spinal disability and physical disability overall, as measured by standardized indices, as spondylosis patients. No differences were found among the 3 groups of patients for the laboratory tests evaluated. DISH is clearly a distinct disorder with signs and symptoms that distinguish it from other causes of spinal complaint and from healthy individuals. It has the potential to cause major disability. Future studies need to address the natural history of DISH, pursue pathogenic mechanisms, and evaluate treatment modalities.

Activities of Daily Living

The importance of the ERCC1/ERCC4[XPF] complex for hypoxic-cell radioresistance does not appear to derive from its participation in the nucleotide excision repair pathway.

The repair-deficient mutant rodent cell lines UV20 and UV41, which are defective in the ERCC1/ERCC4[XPF]-mediated 5'-endonuclease activity, are unusually sensitive to gamma-irradiation under hypoxic (but not oxic) conditions. Because this 5'-endonuclease appears to be involved in two distinct (but overlapping) DNA-repair pathways-the nucleotide excision repair pathway and the recombination-dependent pathway for the removal of DNA interstrand cross-links-it is unclear which of these defective activities is responsible for the hypoxic radiosensitivity of UV20 and UV41 cells. Accordingly, we have extended these measurements to the UV5 and UV24 lines which carry mutations in the ERCC2[XPD] and ERCC3[XPB] genes, respectively; both of these genes encode DNA helicases. These two mutants display a sensitivity to ultraviolet light that is similar to that of UV20 and UV41 cells, reflecting their defect in the incision step of the nucleotide excision repair pathway. However, neither UV5 nor UV24 cells are especially cross-sensitive to agents that produce DNA interstrand cross-links, suggesting that the ERCC2 and ERCC3 activities are not crucial for the repair of these lesions. We show that neither UV5 nor UV24 cells exhibit the unusual hypoxic radiosensitivity that characterizes UV20 and UV41 cells. Based on these data and on a comparison of the patterns of cross-sensitivity of these various mutants to other DNA-damaging agents, we conclude that the increased hypoxic radiosensitivity observed in the UV20 and UV41 mutants is due to a defect in the ERCC1/ERCC4-dependent pathway for the repair of DNA cross-links and not in the nucleotide excision repair pathway. The evidence suggests that this sensitivity may be mediated by some type of radiation-induced cross-links, possibly DNA-protein cross-links.

Alkylating Agents

Oil bioremediation using insoluble nitrogen source.

Oil bioremediation is limited by the availability of nitrogen and phosphorous, which are needed by the bacteria and not present in sufficient amounts in hydrocarbons. The supply of these two essential elements as water-soluble salts presents several problems. These include the rapid dilution of the salts in the large volumes of polluted land or water and their utilization by other bacteria that do not degrade oil. In addition, increasing the concentration of mobile nitrogen creates further environmental problems. The use of hydrophobic sources of nitrogen and phosphorous that have a low water solubility can overcome these problems. We have studied one such compound. F-1, that is not used by most bacteria but serves as a good nitrogen and phosphorous source for those bacterial strains that are capable of utilizing it. We have shown that bacteria using F-1 do not cross-feed other bacterial strains. Moreover, when the concentration of the pollutant is sufficiently reduced, the multiplication of the bacteria slows down until they become a negligible fraction of the bacterial population. Chemical analysis indicated that following a 28-day treatment of Alaskan crude oil, most of the hydrocarbons, including polycyclic aromatics, are degraded to undetectable levels. The C34 and C35 components were also degraded, although their degradation was not completed within this time period. In treatment of a sandy beach that was accidentally polluted with crude heavy oil, about 90% degradation was obtained within about 4 months at an outside average temperature of 5 -10 degrees C.

Biodegradation, Environmental

Cadmium binding by bacteria: screening and characterization of new isolates and mutants.

A fast and simple methodology was developed that enables screening of microbial strains for their ability to bind cadmium. It is based on the use of a radioisotope of cadmium (109Cd) for screening colonies and for evaluation of cadmium binding. The methods described here can be used to screen new environmental isolates or to obtain mutants with altered ability to bind cadmium. Examples for the two uses are described in the paper.

Bacteriological Techniques

ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.

In this study, the relationships between cellular oxygen enhancement ratios (OER) and nucleotide excision repair capability were examined using the UV20 mutant cell line (which has a defective ERCC1 gene). Using a clonogenic survival assay, the OER for the killing of wild-type AA8 cells was 3.2 +/- 0.1, whereas that for UV20 cells was only 2.35 +/- 0.05; the decreased OER of UV20 cells was the result of their significantly greater radiosensitivity relative to wild-type cells under hypoxic conditions. In AA8 cells, hypoxia protected against DNA double-strand break (dsb) induction (determined by pulsed-field gel electrophoresis) by a factor 3.5 +/- 0.3; i.e. to a similar extent that it modulated cell killing. However, this correlation was not apparent in UV20 cells, where hypoxia protected against dsb induction to a similar extent as in wild-type cells (approximately 3.2-fold). Stably transfected UV20 cells over-expressing a full-length ERCC1 cDNA clone displayed a normal OER (3.5 +/- 0.1) in addition to wild-type resistance to UV light. Our data suggest that the hypoxic radiosensitivity of UV20 cells is a direct result of their ERCC1 deficiency and reflects their inability to process some type of DNA damage (not dsbs) that is induced preferentially in hypoxic cells.

Animals

Correlation of expression of connexin mRNA isoforms with degree of cellular differentiation.

Examination of rat hepatic cell lines has revealed a correlation between the differentiated state of the cells and the gap junctional proteins, or connexins, they express. The cell lines RLC (Gershenson et al, 1970) and FTO.2B (Killary et al, 1984) were examined and compared to primary adult hepatocytes for expression of fetal and adult hepatic antigens under various tissue culture conditions. Maximal expression of fetal antigens was observed in cells grown in serum-supplemented medium, on either tissue culture plastic or type IV collagen. Maximal expression of adult specific antigens was seen in cells grown in a hormonally defined medium containing heparin, on type I or type IV collagen. The cell line RLC strongly expressed fetal antigens, while FTO.2B expressed both fetal and adult antigens. These cell lines and another poorly differentiated hepatic cell line, WB-F344 (Tsao et al., 1984) were used to assess the developmental profile of mRNAs encoding isoforms of gap junctions: connexins 26, 32, and 43. The cell lines each transcribed mRNAs of all three connexins, as determined by transcriptional elongation analysis. By contrast, only certain of the connexin mRNAs could be detected in specific cell lines by Northern analysis: RLC expressed only connexin 43 mRNA; WB-F344 expressed connexin 32 and 43 mRNAs. Selection among the connexin mRNAs appears to occur post-transcriptionally. Culture of the cell lines in hormonally defined medium vs. serum supplemented medium did not affect the patterns of connexin mRNA abundance. When the cell lines were cultured in hormonally defined medium containing heparin, however, the level of connexin mRNAs did vary: Connexin 26 mRNA increased in WB-F344 cells, and connexins 32 and 43 mRNAs increased in FTO.2B, but connexin 43 mRNA decreased in WB-F344 and RLC. The abundance of connexin mRNAs also varied when the cell lines were analyzed at different cell densities: connexin 43 mRNA increased with cell density in RLC and WB-F344, and connexin 26 mRNA peaked at an intermediate density and fell at higher cell densities in WB-F344. The differences in connexin mRNA expression among cell lines characteristic of different stages of hepatic differentiation, and the differences in regulation of connexin mRNAs in the hepatic cell lines, suggest distinct biological roles of the highly homologous proteins. Moreover, connexin gene expression may be a marker of hepatic development: as hepatocytes differentiate the proportions of connexin 43 then 26 mRNAs decrease while that of connexin 32 mRNA increases.

Animals

Primary-care quality improvement of mammography rates: a baseline study.

UNLABELLED: In order to improve mammography screening rates, a primary-care physician group in Hartford County studied mammogram compliance rates, and reasons for noncompliance, in a group of 722 women, aged 50 to 64 years. RESULTS: During the two-year study period, 598 (82.8%) of the patients had a mammogram and 16 were lost to follow-up. Of the 108 women without mammograms, six did not think that one was recommended. The test was not indicated for four. Forty did not follow through with recommendations, nine avoided mammograms out of fear, and 11 refused mammograms or physician visits. Thirty-seven others had a mammogram scheduled or performed during the next year. CONCLUSIONS: Several hypothetical strategies for improving compliance are suggested by these results: computer notification of patients of upcoming and overdue due dates, supportive exploration of patients' resistances and fears, phone reminders from primary care physician offices, preventive medicine "tickler files," and coordination across specialties.

Connecticut

The need for liver transplantation: a nationwide estimate based on consensus review.

Orthotopic liver transplantation (OLT) is widely practised in developed countries. The procedure is costly, the supply of donor organs limited, and it is not known how many patients need transplantation. A community-wide estimate of the needs for OLT was performed over two years in all general hospitals in Israel. Records of 1851 patients with liver disease were screened to identify those who might eventually need OLT. The annual estimate of transplantation needs in the country was 10-15.5 per million population, with equal numbers of males and females. The addition of patients with nonreformed alcoholism and end-stage liver disease, originally set as an exclusion criteria, would have added 20% to this estimate. 37% of potential candidates were under 40 years of age at diagnosis, and about 50% were 55-64 years old. Almost 80% of patients had cirrhosis of the liver and 13.6% had fulminant hepatitis. These findings provide a basis for a national plan of OLT in Israel, and similar studies might be useful in other countries.

Adolescent

Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?

An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins (PBPs) with approximate molecular sizes of 94, 82, 52, and 37 kDa were detected by fluorography of [3H]penicillin-radiolabeled membrane proteins prepared from M. tuberculosis H37Ra. The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics. Therefore, ampicillin affinity chromatography was used to purify these four PBPs from crude membranes in order to assay the binding affinities of beta-lactam antibiotics. Ampicillin, amoxicillin, and imipenem, beta-lactam antibiotics previously reported to be active in vitro against M. tuberculosis, bound to M. tuberculosis PBPs at therapeutically achievable concentrations. Binding of the 94-, 82-, and 52-kDa PBPs, but not the 37-kDa PBP, was associated with antibacterial activity, suggesting that these PBPs are the critical targets. Studies of mycobacterial cell wall permeability, which was assayed with a panel of reference cephalosporins and penicillins with different charge positivities, indicated that the rate of penetration of beta-lactam antibiotics to the target PBPs could not account for resistance. Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M. tuberculosis resistance to beta-lactam antibiotics. These findings confirm in vitro data that M. tuberculosis is susceptible to some beta-lactam antibiotics. Further evaluation of these drugs for the treatment of tuberculosis in animal models and in clinical trials is warranted.

Animals

Alasan, a new bioemulsifier from Acinetobacter radioresistens.

Acinetobacter radioresistens KA53, isolated by enrichment culture, was found to produce an extracellular, nondialyzable emulsifying agent (referred to as alasan) when grown on ethanol medium in a batch-fed reactor. The crude emulsifier was concentrated from the cell-free culture fluid by ammonium sulfate precipitation to yield 2.2 g of emulsifier per liter. Alasan stabilized a variety of oil-in-water emulsions, including n-alkanes with chain lengths of 10 or higher, alkyl aromatics, liquid paraffin, soybean and coconut oils, and crude oil. Alasan was 2.5 to 3.0 times more active after being heated at 100 degrees C under neutral or alkaline conditions. Emulsifying activity was observed over the entire pH range studied (pH 3.3 to 9.2), with a clear maximum at pH 5.0. Magnesium ions stimulated the activity both below (pH 3.3 to 4.5) and above (pH 5.5 to 9.3) the pH optimum. Alasan activity was higher in 20 mM citrate than in 20 mM acetate or Tris-HCl buffer. Preliminary chemical characterization of alasan indicated that it is a complex of an anionic, high-molecular-weight, alanine-containing heteropolysaccharide and protein.

Acinetobacter

Correlation of expression of transcription factor C/EBP alpha and surfactant protein genes in lung cells.

C/EBP alpha is a transcription factor which can stimulate expression of genes in lipid-metabolizing epithelial cells. We have detected an increase in mRNA for C/EBP alpha in lungs of fetal rats between days 18 and 20 of gestation, correlating with events occurring during the maturation of the surfactant system, such as an increase in the amount of surfactant protein A mRNA. We have found that C/EBP alpha mRNA levels are substantially enriched in type II alveolar epithelial cells purified from adult lung and that the C/EBP alpha protein is present in type II cell nuclei. When the type II cells are removed from the lung and purified, the protein is rapidly lost. However, both surfactant protein gene expression and C/EBP alpha reappear when cells are plated on Matrigel. Levels of C/EBP alpha mRNA from purified cells decline much more slowly than the protein and are still detectable 48 h after cells have been plated on standard tissue culture plastic. We have also detected the C/EBP alpha protein in nuclear extracts of NCI-H441, a lung-derived cell line that expresses surfactant proteins A and B, but not in A549, a lung-derived cell line which does not express the surfactant proteins. Our data suggest that C/EBP alpha is involved in the development and maintenance of the surfactant system in lung type II cells.

Animals