Q & A : Alzheimer's disease.

Mode of access: Internet.

The self-instructional manual for tumor registrars /

Originally prepared for the Louisiana Regional Medical Program.

Administrative practices supplement to the NIH Guidelines for research involving recombinant DNA molecules : policies and administrative procedures for recombinant DNA research subject to the NIH Guidelines /

"June 1979."

Check your weight and heart disease : I.Q. /

Mode of access: Internet.

DHEW obligations to medical schools, fiscal years 1967-1969.

This publication was prepared by Richard Giza and Catherine Burns under the direction of Dr. Herbert H. Rosenberg.

Proceedings.

"Sponsored by the Division of Research Grants, National Institutes of Health, Bethesda, Maryland."

Annual lectures.

Mode of access: Internet.

Report of the National Conference on Diabetes : Current Status and Future Directions, October 9-12, 1979, Sheraton International Conference Center, Reston, Virginia : appendix to the third Annual report of the National Diabetes Advisory Board /

"April 1980."

Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson`s Disease

Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher`s disease, among patients with Parkinson`s disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson`s disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson`s disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. Conclusions Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson`s disease.

Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from similar to 250 kb to similar to 2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2.

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome

Background: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. Aim: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. Results: We estimate the prevalence of the syndrome to be 1 in 16 000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p< 10(25)). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

Predictors of weight stability in women and men: The aerobic center longitudinal study, 1987--1995

It is estimated that more than half the U.S. adult population is overweight or obese as classified by a body mass index of 25.0–29.9 or ≥30 kg/m 2, respectively. Since the current treatment approaches for long-term maintenance of weight loss are lacking, the National Institutes of Health state that an effective approach may be to focus on weight gain prevention. There is a limited body of literature describing how adults maintain a stable weight as they age. It is hypothesized that weight stability is the result of a balance between energy consumption and energy expenditure as influenced by diet, lifestyle, behavior, genetics and environment. The purpose of this research was to examine the dietary intake and behaviors, lifestyle habits, and risk factors for weight change that predict weight stability in a cohort of 2101 men and 389 women aged 20 to 8 7 years in the Aerobic Center Longitudinal Study regardless of body weight at baseline. At baseline, participants completed a maximal exercise treadmill test to determine cardiorespiratory fitness, a medical history questionnaire, which included self-reported measures of weight, dietary behaviors, lifestyle habits, and risk factors for weight change, a three-day diet record, and a mail-back version of the medical history questionnaire in 1990 or 1995. All analyses were performed separately for men and women. Results from multivariate regression analyses indicated that the strongest predictor of follow-up weight for men and women was previous weight, accounting for 87.0% and 81.9% of the variance, respectively. Age, length of follow-up and eating habits were also significant predictors of follow-up weight in men, though these variables only explained 3% of the variance. For women, length of follow-up and currently being on a diet were significantly associated with follow-up weight but these variables explained only an additional 2% of the variance. Understanding the factors that influence weight change has tremendous public health importance for developing effective methods to prevent weight gain. Since current weight was the strongest predictor of previous weight, preventing initial weight gain by maintaining a stable weight may be the most effective method to combat the increasing prevalence of overweight and obesity. ^

Clinical anatomy of the European hamster Cricetus cricetus, L. /

Mode of access: Internet.

A Mortality study of 1.3 million persons by demographic, social and economic factors : 1979-1985 follow-up : U.S. National Longitudinal Mortality Study /

Chiefly tables.

Foods for health : report of the pilot program : a pilot nutrition education program by Giant Food Inc. in cooperation with the National Heart, Lung, and Blood Institute /

"August 1983."