Search PubMed⌕ Search

Biomedical subjects

M Schwab

Publications and source records attributed to M Schwab.

At least 181 records · Page 10Linked to original sources
PubMed1994

Personal exposure to nitrogen dioxide in the Los Angeles Basin.

A large scale study of human exposure to nitrogen dioxide (NO2) was conducted in the Los Angeles Basin, the only metropolitan area in the United States that exceeds the NO2 NAAQS. Data are available for a population representative sample of 482 households and 682 individuals. Personal exposures, as well as indoor and outdoor home levels, were monitored using passive time-integrating filter badges. Monitoring extended over a one-year period (May 1987 to May 1988), with each individual providing two consecutive days of data. Information was also collected on activity patterns, household and personal characteristics, and spatial and temporal variables. This paper describes the study design, summarizes the sample characteristics and representativeness, and presents the distribution of personal, indoor, and outdoor NO2 concentrations recorded by the monitors. Over the entire sample, median personal and outdoor levels were 35 ppb; median indoor levels were 24 ppb. Personal exposures for those in homes with gas ranges with pilot lights average 10 ppb greater than those with electric ranges, and 4 ppb greater than those with gas ranges without pilot lights. Forty percent of the variation in indoor concentrations is explained by outdoor levels; 59 percent of the variation in personal exposures is explained by indoor levels; and 48 percent of the variation in personal exposures is explained by outdoor levels.

Adolescent↗
PubMed1994

Where pathology meets molecular biology: N-myc amplification in human neuroblastoma as a paradigm for the clinical use of an oncogene alteration.

Increase of the dosage of cellular oncogenes by DNA amplification is a frequent genetic alteration of cancer cells. The presence of amplified cellular oncogenes is usually signalled by conspicuous chromosomal abnormalities, "double minutes" (DMs) or "homogeneously staining chromosomal regions" (HSRs). Some human cancers carry a specific amplified oncogene at high incidence. In neuroblastomas the amplification of N-myc has been found associated with aggressively growing cancers and is an indicator for poor prognosis. N-myc amplification is of predictive value for identifying neuroblastoma patients that require specific therapeutic regimens and for identifying patients that do not benefit from chemotherapy.

Animals↗
PubMed1994

Nitrogen dioxide and respiratory illness in children. Part III: Quality assurance in an epidemiologic study.

This report describes the quality assurance and quality control program developed for the previously reported epidemiologic study of nitrogen dioxide (NO2) and respiratory illness in children (Health Effects Institute Research Report 58, Parts I and II). The specific aims of the program were to make certain that data were sufficiently accurate, complete, verifiable, and retrievable. The quality assurance and quality control program consisted of: a written protocol, standard operating procedures, written records, a project management system, appropriate data processing, data verification, and data analysis planning, and was staffed by qualified and appropriately trained personnel. Within the activities of the overall program, two focused quality assurance studies were conducted. During the first of these focused studies, parents maintained a calendar-diary of their child's daily respiratory symptoms. Telephone interviews were conducted at intervals of two weeks, and parents used the calendars to report on symptom occurrence since the previous call. To assess the comparability of illness events based on symptom reports from the parents with usual clinical diagnostic methods, nurse practitioners examined children during illness, and office and clinic records of outpatient visits were reviewed. Using the parent reports, respiratory illnesses were defined as symptom episodes of at least two consecutive days; lower respiratory illnesses included at least one day of either wet cough or wheeze. Runny or stuffy nose was reported for 93% of illnesses; and wet cough for 33% and wheeze for 6% of illnesses. In comparison with the diagnoses made by a nurse practitioner, parent reports of wet cough or wheeze were sensitive (93.4%) for detecting lower respiratory illnesses, but nonspecific (with specificity of only 24.2%). The majority of the false-positive lower respiratory illnesses had the symptom of wet cough. The comparison of parent reports with outpatient records provided similar findings. These findings indicate that standardized reporting of respiratory illnesses can be achieved with regular telephone interviews, but the classification of specific illnesses from the observations of parents' information may differ from diagnoses made by clinicians. The second focused quality assurance study evaluated the measurement error associated with the parents' use of passive diffusion samplers for NO2. Midway through the study, technicians conducted home visits to assess compliance with stated procedures, and to make independent measurements of NO2. Based on criteria for placement and use of the samplers, conditions of noncompliance were observed on about 40% of visits.(ABSTRACT TRUNCATED AT 400 WORDS)

Data Collection↗
PubMed1994

Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells.

Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). We report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the integration of fragments into various marker chromosomes. As a consequence, 17q material can increase over 17p material. The nonrandom frequency of 1;17 translocations appears to indicate an as-yet-undefined contribution to neuroblastoma development.

Chromosome Banding↗
PubMed1993

Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin.

The human fibroblast activation protein (FAP), defined by monoclonal antibody F19, is expressed in vivo in reactive stromal fibroblasts of epithelial cancers, subsets of bone and soft tissue sarcomas, and granulation tissue of healing wounds. FAP is generally absent from the stroma of benign epithelial tumors and normal adult tissues. In vitro FAP induction is observed in proliferating cultured fibroblasts and in melanocytes grown with fibroblast growth factor and phorbol ester. In the present study, we show that fibroblast and melanocyte FAP is a cell surface protein comprising noncovalently linked M(r) 95,000 (p95) and M(r) 105,000 (p105) subunits. In contrast, cultured sarcoma and melanoma cell lines express only p95 or are FAP negative. Immunoblot experiments show that p95, but not p105, carries the epitope defined by monoclonal antibody F19. Furthermore, peptide maps of purified p95 and p105 differ, suggesting that they may be distinct gene products. Loss of FAP or a change from p95/p105 to p95 expression accompanies the acquisition of growth factor independence and tumorigenicity in several in vitro test systems, including simian virus 40 transformation of normal fibroblasts, Ha-ras transformation of normal melanocytes, supertransformation of osteosarcoma cells, and enhanced N-MYC expression in variant neuroblastoma cells, whereas serum-starved normal fibroblasts continue to express p95/p105. Thus, fAP expression appears to be linked to the growth factor-dependent proliferative capacity of normal cells and is not merely a secondary event in proliferating cells; furthermore, FAP expression is inversely correlated with growth factor independence and tumorigenicity in transformed cell lines. This distribution pattern is consistent with a role for p95/p105 in mediating extrinsic, growth regulatory signals in normal cells, possibly as a heteromeric cell surface receptor. Such a physiological function may be obviated when oncogenes with cytoplasmic or nuclear sites of action are activated, reducing extrinsic growth factor dependence and permitting down-regulation of FAP in certain transformed cells.

Antigens, Neoplasm↗
PubMed1993

Respiratory and irritant health effects of ambient volatile organic compounds. The Kanawha County Health Study.

Kanawha County, West Virginia, is one of the largest chemical manufacturing centers in the United States. In 1988, a survey of respiratory and irritant symptoms was administered to all third grade to fifth grade children attending 74 elementary schools in Kanawha County, and concentrations of 15 volatile organic compounds were measured at each school. Exposures were characterized by school location, by the sum of the concentrations of five petroleum-related compounds, and by the sum of the concentrations of 10 compounds more specific to industrial processes. Children enrolled in schools within the valley had higher rates of doctor-diagnosed asthma (odds ratio (OR) = 1.27, 95% confidence interval (CI) 1.09-1.48) and a higher score on a composite indicator of five chronic lower respiratory symptoms (OR = 1.13, 95% CI 1.02-1.26) than children who were enrolled in schools outside of the valley. The incidence of chronic respiratory symptoms was also positively associated with the concentrations of volatile organic compounds. The estimated change in the odds ratio for chronic lower respiratory symptoms associated with a 2-micrograms/m3 change in process-related compounds was 1.08 (95% CI 1.02-1.14). No consistent pattern was found between acute irritant symptoms in the 2 weeks preceding questionnaire administration and either proximity to industry or exposure to volatile organic compounds. The authors conclude that exposure to volatile organic compounds, including emissions from chemical manufacturing plants, is associated with increased rates of chronic respiratory symptoms characteristic of reactive airways.

Air Pollutants↗
PubMed1993

Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system.

A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.

Adolescent↗
PubMed1993

DNA amplification in human gastric carcinomas.

We recently identified a genomic domain at chromosome 10q26 that is highly amplified in the gastric carcinoma cell lines KATO III and SNU-16 and contains the BEK/K-sam gene, which encodes several growth factor receptors. A contiguous segment of 200 kb spanning this gene was amplified in five of 139 (3.6%) primary gastric carcinomas, all of them classified as poorly differentiated tumors. There was no amplification of this genomic region in a variety of other solid tumors. The overall frequency of gene amplification among the gastric carcinomas rose to 19.4% when MYC, ERBB2, and INT2 were included in the analysis, with significant association with advanced tumor stage. Amplification of various genomic regions in solid tumors may be more frequent than previously estimated.

Carcinoma↗
PubMed1993

TraM of plasmid R1 regulates its own expression.

Regulation of the traM gene, which encodes a factor essential for conjugation of resistance plasmid R1, was studied in vivo using translational gene fusion. traM"lacZ fusion constructs were transferred to the chromosome via the recombinant phage lambda RZ5. The level of beta-galactosidase expressed by the lysogens indicates that the traM promoters are very active. Expression of traM was diminished five- to sixfold when the single-copy plasmids R1 or R1-19 were present in trans. When recombinant plasmids carrying traM were present at higher copy numbers, traM expression was reduced as much as 45-fold. The negative effect of R1 plasmids on traM expression in trans, which we interpret as autoregulation, was observed regardless of whether the plasmids were conjugatively repressed or derepressed. Site-specific mutagenesis of the region encoding the N-terminus of the TraM protein eliminated the autoregulative effect indicating that the N-terminal amino acids of the protein are important to its DNA-binding function. The autoregulatory behaviour of TraM is allele specific. R1- or P307-encoded TraM molecules were found to recognize only the cognate DNA.

Amino Acid Sequence↗
PubMed1993

Nitrogen dioxide and respiratory illnesses in infants.

Nitrogen dioxide is an oxidant gas that contaminates outdoor air and indoor air in homes with unvented gas appliances. A prospective cohort study was carried out to test the hypothesis that residential exposure to NO2 increases incidence and severity of respiratory illnesses during the first 18 months of life. A cohort of 1,205 healthy infants from homes without smokers was enrolled. The daily occurrence of respiratory symptoms and illnesses was reported by the mothers every 2 wk. Illnesses with wheezing or wet cough were classified as lower respiratory tract. Indoor NO2 concentrations were serially measured with passive samplers place in the subjects' bedrooms. In stratified analyses, illness incidence rates did not consistently increase with exposure to NO2 or stove type. In multivariate analyses that adjusted for potential confounding factors, odds ratios were not significantly elevated for current or lagged NO2 exposures, or stove type. Illness duration, a measure of illness severity, was not associated with NO2 exposure. The findings can be extended to homes with gas stoves in regions of the United States where the outdoor air is not heavily polluted by NO2.

Air Pollutants↗
PubMed1993

Nitrogen dioxide and respiratory illness in children. Part I: Health outcomes.

We have carried out a prospective cohort study to test the hypothesis that exposure to nitrogen dioxide increases the incidence and severity of respiratory infections during the first 18 months of life. Between January 1988 and June 1990, 1,315 infants were enrolled into the study at birth and followed with prospective surveillance for the occurrence of respiratory infections and monitoring of nitrogen dioxide concentrations in their homes. The subjects were healthy infants from homes without smokers; they were selected with stratification by type of cooking stove at a ratio of four to one for gas and electric stoves. Illness experience was monitored by a daily diary of symptoms completed by the mother and a telephone interview conducted every two weeks. Illnesses with wheezing or wet cough were classified as involving the lower respiratory tract; all other respiratory illnesses were designated as involving the upper respiratory tract. Exposure to nitrogen dioxide was estimated by two-week average concentrations measured in the subjects' bedrooms with passive samplers. This analysis is limited to the 1,205 subjects completing at least one month of observation; of these, 823 completed the full protocol, contributing 82.8% of the total number of days during which the subjects were under observation. Incidence rates for all respiratory illnesses, all upper respiratory illness, all lower respiratory illnesses, and lower respiratory illness further divided into those with any wheezing, or wet cough without wheezing, were examined within strata of nitrogen dioxide exposure at the time of the illness, nitrogen dioxide exposure during the prior month, and type of cooking stove. Consistent trends of increasing illness incidence rates with increasing exposure to nitrogen dioxide were not evident for either the lagged or unlagged exposure variables. The effect of nitrogen dioxide exposure on illness occurrence during at-risk intervals of two weeks' duration was examined using the generalized estimating equation approach. In these multivariate analyses, none of the odds ratios was significantly elevated for unlagged nitrogen dioxide exposures, lagged nitrogen dioxide exposures, or stove type. Duration of illness was assessed in relation to the same exposure variables; illness duration and nitrogen dioxide exposure were not associated. We have found that indoor exposure to nitrogen dioxide is associated with neither the incidence nor the duration of respiratory illnesses. The study was designed to have sufficient power to detect effects of nitrogen dioxide exposure of magnitudes previously reported and in a range relevant to public health concern; the lack of association cannot be attributed to potential bias from misclassification of outcome or exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants↗
PubMed1993

Nitrogen dioxide and respiratory illness in children. Part II: Assessment of exposure to nitrogen dioxide.

Repeated measurements of nitrogen dioxide were obtained from 1988 to 1991 in the homes of 1,205 infants living in Albuquerque, NM. Passive diffusion samplers were used to obtain a series of two-week integrated measurements from the home of each infant for use in a cohort study of the relation of residential exposure to nitrogen dioxide and respiratory illnesses. Information on stove use and time spent inside the residence was collected at two-week and two-month intervals, respectively. During the winter, in the bedrooms of homes with gas cooking stoves, mean nitrogen dioxide concentrations were 21 parts per billion (ppb); mean concentrations in the living room and kitchen were 29 ppb and 34 ppb, respectively. In homes with electric cooking stoves, the mean bedroom concentration was 7 ppb during the winter. Lower indoor concentrations were observed during the summer in homes with both gas and electric stoves. On average, infants spent approximately 12.3 hours per day in their bedrooms, 7.3 hours in the living rooms, 35 minutes in the kitchens, and 3.8 hours out of their homes. (As a condition of participation, none of the infants spent more than 20 hours per week in day care outside of their homes). The mean time infants spent in the kitchen during cooking was approximately nine minutes per day. We tested whether exposures of infants living in homes with gas stoves could be reasonably estimated by measurements in the bedroom in comparison with time-weighted average concentrations based on time-activity data and simultaneous nitrogen dioxide measurements in the kitchen, living room, and bedroom. In 1,937 two-week intervals from 587 infants, 90% of time-weighted exposure (on the three-level classification used in this study) estimates were in agreement with estimates based on bedroom concentrations alone. The agreement of the time-weighted nitrogen dioxide exposure estimates with the bedroom concentrations is attributed to limited amounts of cooking stove use (the mean was 29 minutes per day), small room-to-room differences in nitrogen dioxide concentrations (the mean kitchen-bedroom difference was 12 ppb), and the relatively large proportion of time that infants spent in their bedrooms.

Air Pollution, Indoor↗
PubMed1993

Translocation junctions cluster at the distal short arm of chromosome 1 (1p36.1-2) in human neuroblastoma cells.

Human neuroblastoma cells show at high frequency structural changes of the distal short arm of chromosome 1 (1p). The commonly altered region has been identified in previous loss-of-heterozygosity (LOH) studies to involve deletion of 1p36.1-2. These bands are also the site of constitutional alterations in patients with neuroblastoma. In an approach to define the 1p36.1-2 alterations in more detail we here employ four neuroblastoma cell lines to map translocation breaks involving 1p36.1-2 by fluorescence in situ hybridization (FISH). A chromosomal interval flanked by loci DIS96 and DIS98 contained translocation junctions in each of four lines. This analysis identifies in 1p a restricted genomic region as involved in chromosomal rearrangement in different neuroblastomas. The specificity of neuroblastoma translocation junctions at the molecular level implicates this genomic region in tumor development.

Chromosome Banding↗
PubMed1993

Activation of gene transcription by the amino terminus of the N-Myc protein does not require association with the protein encoded by the retinoblastoma suppressor gene RB1.

N-Myc encodes a nuclear phosphoprotein that contains a basic region (BR), a helix-loop-helix (HLH) and a leucine zipper (Zip). These motifs are hallmarks of certain transcription factors. In pursuit of the question if N-Myc can activate transcription, we have employed an experimental model involving the yeast transcription factor Gal4. We have first generated fusion proteins containing the Gal4 DNA-binding domain joined to portions of N-Myc. Subsequently we have analysed if chimeric proteins can transactivate the transcription of a reporter under the control of Gal4 binding sites. Here we show that the amino terminal portion of N-Myc activates transcription. Activation maps to a domain highly conserved among Myc-proteins and to other non-conserved sequences, suggesting functional redundancy. Previous studies had documented in vitro association of the RB1 protein with N-Myc (Rustig et al., 1991). We here confirm this observation and identify the region encompassing the transactivation domain as responsible for RB1 binding. Analyses of N-Myc transactivation in retinoblastoma cell line WERI lacking a function RB1 protein gave results similar to those with cell lines having an intact RB1 protein, showing that RB1 protein is not required for transactivation by N-Myc. The present findings leave open the question if deregulated expression of N-Myc contributes to tumorigenesis by transcriptional activation of as yet unidentified target genes or by functionally inactivating the protein encoded by the tumor suppressor gene RB1, or by a combination of both.

DNA-Binding Proteins↗
PubMed1993

Amplification of N-myc as a prognostic marker for patients with neuroblastoma.

N-myc is amplified between 5 and several hundred-fold frequently in neuroblastomas and, at lower frequency, in other human cancers with neuronal qualities, including retinoblastomas, gliomas, astrocytomas and small cell lung cancers. In neuroblastomas N-myc amplification is significantly correlated with poor prognosis; for other types of tumors such a correlation is difficult to make, due to low incidence of amplification. Amplification is associated with elevated expression, both of mRNA and protein. N-myc encodes two polypeptides of relative masses of 62 and 64 kDa, which are phosphorylated, at least in vitro, by casein kinase II and that are localized in the nucleus. There they can associate in vivo with another protein, Max, through a C-terminal dimerization motif, the leucine zipper. An N-terminal portion of N-myc, referred to as 'Myc-boxes', can substitute for the transcription-activating function of the yeast transcription factor Gal 4, thus raising the possibility that N-myc itself may act as a transcription factor, either alone or in association with other factors.

Animals↗