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M Schenker

Publications and source records attributed to M Schenker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: the German BABYDIAB study.

AIMS/HYPOTHESIS: Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus. The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity. METHODS: HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up: 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age. RESULTS: The HLA genotypes DRB1*03/04(DQB1*57non-Asp) and DRB1*04/04(DQB1*57non-Asp) were present in 7.1% and 5.0% of offspring of parents with Type I diabetes. The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3% vs 5.5%, odds ratio 6.3 [p = 0.002] and 22.7% vs 4.2%, odds ratio 6.6 [p = 0.003]) and half of all offspring who developed antibodies had these genotypes. Other genotypes were not associated with an increase in risk. By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20% (95% CI 9.4,30.6) for offspring carrying either the DRB1*03104(DQB1*57non-Asp) or the DRB1*04/04(DQB1*57non-Asp) genotype compared with 2.7% (95% CI 1.2,4.2) for offspring without these genotypes (p < 0.0001). CONCLUSION/INTERPRETATION: These data show that early appearance of islet autoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homozygous offspring and indicate that primary prevention could be considered once available in an offspring cohort selected for these genotypes.

Adult↗
PubMed1999

Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study.

The temporal development of autoantibodies was studied in 1,353 offspring of parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring had islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detected thereafter were likely to represent a true de novo production, since prevalences were the same for offspring from mothers and fathers with diabetes, antibodies detected at 9 months were almost always confirmed in the 2-year sample and were associated with an increased likelihood of having or developing other antibodies. By 2 years of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody. IAAs were detected most frequently, and few had autoantibodies in the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional antibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk.

Aging↗
PubMed1998

GADIA2-combi determination as first-line screening for improved prediction of type 1 diabetes in relatives.

A new radiobinding assay for the simultaneous detection of antibodies to GAD and the tyrosine phosphatase IA2 has been recently described in patients with newly diagnosed type 1 diabetes. Here we assessed sensitivity and predictive value of this GADIA2-combi test in first-degree relatives of type 1 diabetic patients compared with islet cell antibody (ICA) and insulin autoantibody (IAA) screening. Of 1,606 relatives, 77 (4.8%) had elevated GADIA2-combi titers above the 99th percentile of 105 nondiabetic control subjects, and results were confirmed by testing these samples for GAD antibody (GADA) and tyrosine phosphatase IA2 antibody (IA2A) in the single antibody test (29 GADA+/IA2A+, 44 GADA+/IA2A-, and 4 IA2A+/GADA-). A further 9 of 1,606 relatives had detectable ICA (1) or IAA (8), but they were negative in the GADIA2-combi assay as well as in the single test for GADA or IA2A. Twenty-four relatives progressed to IDDM within a median follow-up time of 5.6 years (range 0.5-8.2). The sensitivity of antibody determination in relatives with progression to IDDM was 92% for the GADIA2-combi assay, 96% for the combined testing of IAA and GADIA2-combi antibodies, and 83, 67, 67, and 79%, respectively, for GADA, IA2A, IAA, or ICA testing alone. The cumulative life-table risk of antibody-positive relatives was related to GADIA2-combi titers (5-year risk: >50 U, 51% [95% CI 30-73]; >10 to 50 U, 12% [1-24]; <10 U, 0.17% [0-0.5]; P=0.0001) and on the presence of IA2A in addition to GADA (5-year risk: GADA+/IA2A+, 47% [25-68]; GADA+/IA2A-, 15% [2-28]; P=0.006). In those with detectable antibodies, risk was not associated with age (<15 vs. >15 years) or relation to proband (offspring, sibling, parent). Relatives with GADIA2-combi antibodies >10 U and the additional presence of IAA had a slightly higher diabetes risk than relatives without IAA (5-year: IAA+, 46% [23-68]; IAA-, 19% [6-32]; P=0.07). Furthermore, low first-phase insulin release after intravenous glucose tolerance test was associated with risk in relatives with GADIA2-combi antibodies (P=0.01). These results indicate that the GADIA2-combi test is a valuable marker for first-line screening and risk assessment of type 1 diabetes in relatives. It can be used for venous as well as capillary blood samples.

Adolescent↗
PubMed1995

Subunit composition of G(o) proteins functionally coupling galanin receptors to voltage-gated calcium channels.

The neuropeptide galanin is widely expressed in the central nervous system and other tissues and induces different cellular reactions, e.g. hormone release from pituitary and inhibition of insulin release from pancreatic B cells. By microinjection of antisense oligonucleotides we studied the question as to which G proteins mediate the galanin-induced inhibition of voltage-gated Ca2+ channels in the rat pancreatic B-cell line RINm5F and in the rat pituitary cell line GH3. Injection of antisense oligonucleotides directed against alpha 01, beta 2, beta 3, gamma 2 and gamma 4 G protein subunits reduced the inhibition of Ca2+ channel current which was induced by galanin, whereas no change was seen after injection of cells with antisense oligonucleotides directed against alpha i, alpha q, alpha 11, alpha 14, alpha 15, beta 1, beta 4, gamma 1, gamma 3, gamma 5, or gamma 7 G protein subunits or with sense control oligonucleotides. In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently. The latter G protein composition was previously shown to be used by muscarinic M4 receptors to inhibit Ca2+ channels.

Amino Acid Sequence↗
PubMed1994

The private funding of public research. New directions in the administration of occupational and environmental health research.

Dr. Cullen: The experience with the new research models, starting with the prototypic experience of the rubber industry studies of the 1970s and expanding to diverse sectors of American industry in the 1980s, has yielded some important lessons for the future. In closing this symposium I shall try to summarize these briefly. Certain strengths of the evolving process seem common to each of the models. Alone and collectively, the new research arrangements have quite apparently served to increase substantially the pool of funds available to the academic sector for the study of occupational health and safety problems. As a consequence, a larger pool of investigators has participated in the research process, greatly strengthening the future academic capability and experience of our fragilely supported teaching centers. Combined with the involvement of the academic centers in the review process, there has been an undeniable broadening and deepening of the nation's research output and long-term capability in occupational health. On the side of the private sector, the new relationships have led to marked progress in the knowledge base about health and safety problems, with a heavily directed focus on those of greatest relevance to the industries involved. The credibility of the knowledge acquired has been enhanced, an important achievement in a society in which perception of truth is often as important as the truth itself! Because of the requirements of the process for broad involvement by the organizations which undertake these activities, health and safety have achieved far greater visibility and attention by corporate and union leaders who may have previously had no involvement in issues of health and safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Spirometry reference values for women and men 65 to 85 years of age. Cardiovascular health study.

Pulmonary function was assessed by spirometry in 5,201 ambulatory elderly participants of the Cardiovascular Health Study, sampled from four communities. A stringent quality assurance program exceeded American Thoracic Society (ATS) recommendations for spirometry. Less than 6% of the participants were unable to perform three acceptable spirometry maneuvers. A "healthy" subgroup of 777 women and men 65 to 85 yr of age was identified by excluding smokers and those with lung disease and other factors determined to independently, significantly, and negatively influence the FEV1. Results from black participants were examined separately. Reference equations and normal ranges for FEV1, FVC, and the FEV1/FVC ratio were determined from the healthy group. The results demonstrate differences in predicted values as great as 20% (0.5 to 1 L) for elderly patients when compared with the spirometry reference equations that are most commonly used in the United States.

Aged↗
PubMed1992

Occupational lung diseases in the industrializing and industrialized world due to modern industries and modern pollutants.

Although most new 'high tech' industrial processes are developed in industrialized countries, many of these technologies are eventually transferred to the industrializing countries. Many of these new technologies are associated with the use of respiratory toxins. However, there has been little study of acute or chronic health effects of work in these industries. The semiconductor industry illustrates many of these issues. The past decade has been increasing globalization of semiconductor manufacturing. Semiconductor manufacturing uses many chemicals with extremely high respiratory toxicity, including gases such as arsine and phosphine, strong acids and bases, dopants and photoactive chemicals. In semiconductor manufacturing, gases and chemicals are strictly controlled, but little is known about the occurrence of respiratory symptoms or disease in this industry. Potential acute respiratory effects of these exposures include mucous membrane irritation, tracheobronchitis, pulmonary edema and death. Chronic effects may include airway sensitization and possibly respiratory cancer. Movement of 'high tech' industries to less industrialized countries may not be accompanied by the same degree of attention to the control of workplace exposures. The shortage of adequately trained health and safety personnel, greater attention to safety than to health issues, and the unorganized and unskilled workforce in industrializing countries may exacerbate this situation. More research is needed on the health effects of exposures in rapidly changing industries such as semiconductor manufacturing, and the results of this research must be communicated and safe practices implemented worldwide.

Antimony↗
PubMed1987

A behavioral evaluation of pest control workers with short-term, low-level exposure to the organophosphate diazinon.

Neurobehavioral effects of short-term, low-level exposure to diazinon were investigated among 99 pest control workers tested before and after their work shift with a computer-assisted neurobehavioral test battery. Each subject completed a brief neurological screening examination, a symptom questionnaire, and tests of concentration, eye-hand coordination, pattern recognition, visual memory, and finger tapping. The diazinon metabolite diethylthiophosphate (DETP) was measured in pre- and post-shift urine samples collected from 46 diazinon applicators applying granulated diazinon onto residential properties with lawn spreaders, and 56 non-applicators. Post-shift median DETP for applicators and non-applicators was 24 and 3 ppb, respectively. Full shift, whole body exposure to diazinon was quantitated for 19 subjects using personal air monitoring and passive badges. Median diazinon exposure for applicators and non-applicators was 2.1 and 0.03 mg, respectively. Mean duration of pesticide application was 39 days (SD = 12 days) before testing. No adverse DETP-related changes in pre- or post-shift neurobehavioral function were found with multiple linear regression models after adjusting for age, sex, education, and ethanol intake, although Symbol-Digit pairing speed was slower among the applicators as a group. The prevalence of 18 symptoms possibly related to diazinon exposure was not elevated among applicators. The study failed to demonstrate diverse behavioral effects of short-term, low-level diazinon exposure in a pest control program which emphasized personal protective equipment and direct supervision.

Adult↗
PubMed1987

Accuracy of spirometric and flow-volume indices obtained by digitizing volume-time tracings.

We tested the accuracy of a new system for deriving standard spirometric indices, maximal expiratory flow rates, and slope ratios from volume-time tracings. A computer-based technique employing a hand-operated cursor was used to put discrete values of volume and time into a memory array. Spirometric values obtained on 102 subjects using the computer system were compared with the corresponding "hand-read" values. The difference between the 2 measuring techniques were not significant for the FVC, the FEV75, and the FEF25-75; however, the average FEV1 differed by 6.7 ml (SD, 20.3 ml), which was significant. In addition, 10 subjects performed FVC maneuvers through a spirometer and flowmeter connected in series. Flows and slope ratios obtained from the volume-time tracings were compared with those obtained directly from the flowmeter. There was a high degree of correlation between the 2 types of flow measurements (r = 0.989), whereas slope ratios were less well correlated (r = 0.589). Configurational detail such as the presence of "bumps" on slope ratio versus volume plots were recovered with the computer technique. Using this new system, it is possible for 1 operator to process 10 to 12 sets of spirometry tracings per hour.

Adolescent↗
PubMed1986

Seven-year follow-up of workers exposed to 1,2-dibromo-3-chloropropane.

A follow-up report was done of workers exposed to 1,2-dibromo-3-chloropropane (DBCP) 7 years after termination of exposure. A 1977 study of male pesticide workers exposed to DBCP in a California agricultural chemical plant identified many who were azoospermic or oligospermic. Sperm concentration and serum follicle-stimulating hormone (FSH) levels in 44 of these workers were reassessed 5 to 8 years after exposure was terminated in 1977. Two of the eight originally azoospermic workers produced sperm during the follow-up, although only one had normal sperm counts. No increase in sperm production could be detected in men who had low sperm counts in 1977, and elevated serum FSH levels did not drop in oligospermic or azoospermic men. These results suggest that permanent destruction of germinal epithelium occurs in most DBCP-sterile persons.

Follicle Stimulating Hormone↗
PubMed1983

The health effects of involuntary smoking.

Involuntary smoking is defined as the exposure of nonsmokers to tobacco combustion products in the indoor environment. Involuntary smokers are exposed to a quantitatively smaller and qualitatively different smoke exposure than active smokers. Quantitation of exposure is particularly difficult in both physiologic and epidemiologic studies. Acute physiologic studies have documented minimal physiologic changes in healthy subjects. However, individuals with heart or lung disease may be differentially affected. A relatively large body of data relates parental (particularly maternal) cigarette smoking to the occurrence of both acute respiratory illnesses and chronic respiratory symptoms in children. The effect seems to be greatest early in life and cannot be separated from in utero exposure. Data linking parental smoking to lower levels of pulmonary function are all cross-sectional and less conclusive. What is apparent is that the magnitude of the direct effect of passive smoke exposure is likely to be relatively small (from 1 to 5% reduction in maximally obtained lung function level in exposed children). Data on adults are insufficient to allow for a quantitative estimate. The important effects of passive smoke exposure in childhood are twofold. The slight reduction in pulmonary function level may predispose individuals to increased risks from environmental agents later in life. In addition, having a parent who smokes substantially increases the likelihood that a child will become a smoker. Finally, two studies have linked lung cancer in nonsmokers to exposure to spouses' cigarette smoke. Further research is needed to confirm these findings. Involuntary smoking may have important health effects, either direct or indirect, which deserve further study.

Adolescent↗