Activating and inactivating mutations in LH receptors

In rats, galanin modulates luteinizing hormone (LH) secretion, and gonadotropin-releasing hormone (GnRH) neurons provide a possible source of this galanin. To understand galanin's physiological role in GnRH neurons, we used double-label in situ hybridization and computerized image analysis to examine the regulation of galanin message in GnRH neurons. We found that galanin gene expression in GnRH neurons is regulated by sex steroids, induced coincident with the LH surge, and persists well after the completion of the LH surge, and that the induction of galanin message in GnRH neurons coincident with the LH surge is sexually differentiated neonatally. We postulate that the rise in galanin gene expression in GnRH neurons at the time of the LH surge serves to replenish galanin released with GnRH that is needed for the production of the LH surge, or that galanin is involved in physiological events that occur subsequent to the LH surge.     

Fetal alcohol syndrome in twins of alcoholic mothers: concordance of diagnosis and IQ

The effects of teratogens can be modified by genetic differences in fetal susceptibility and resistance. Twins of alcoholic mothers provide a unique opportunity to study this phenomenon with respect to alcohol teratogenesis. Sixteen pairs of twins, 5 MZ and 11 DZ, all heavily exposed to alcohol prenatally, were evaluated. They represented all available twins of alcohol-abusing mothers who were on the patient rolls of the authors. The rate of concordance for diagnosis was 5/5 for MZ and 7/11 for DZ twins. In two DZ pairs, one twin had fetal alcohol syndrome (FAS), while the other had fetal alcohol effects (FAE). In 2 other DZ pairs, one twin had no diagnosis while one had FAE. IQ scores were most similar within pairs of MZ twins and least similar within pairs of DZ twins discordant for diagnosis. Despite equivalent alcohol exposure within twin pairs, alcohol teratogenesis appears to be more uniformly expressed in MZ than in DZ twins. These data are interpreted as reflecting the modulating influence of genes in the expression of the teratogenic effects of alcohol.     

Adrenergic receptors and secretory responses of the rat submandibular salivary gland after periodic incisor reduction

While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia.     

Plan and operation of the 1995 National Survey of Family Growth

OBJECTIVES: This report describes how the 1995 National Survey of Family Growth (NSFG) was designed, planned, and implemented. The NSFG is a national survey of women 15-44 years of age designed to provide national estimates of factors affecting pregnancy and birth rates and the health of women and infants. Planning for the 1995 NSFG began in 1990 at a formal conference with the survey's data users. Suggestions for substantial changes and improvements in the survey were made there and carried out by NSFG staff and the NSFG contractor--the Research Triangle Institute (RTI). METHODS: The survey was converted from paper and pencil interviewing to Computer-Assisted Personal Interviewing (CAPI) to improve the quality, consistency, and timeliness of the data. At the same time, event histories of the respondent's work, education, family background, cohabitation, and sexual partners were added to lend explanatory power to the survey. These changes made the interview and the CAPI program long--average interview length was 103 minutes--and complex, but the CAPI program worked very well. RESULTS: About 260 female interviewers were trained for 7 days in January 1995. These interviewers completed a total of 10,847 interviews with women 15-44 years of age, for a response rate of 79 percent. This report describes how the survey was planned and designed and how the data were collected, edited, and processed for public use. This report may be of interest to NSFG data users and to those planning other computer-assisted surveys.     

The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus

Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.     

Survival tucker: improved diet and health indicators in an aboriginal community

The poor nutritional status of Aboriginal Australians is a serious and complex public health concern. We describe an unusually successful health and nutrition project initiated by the people of Minjilang, which was developed, implemented and evaluated with the community. Apparent community dietary intake, assessed by the 'store-turnover' method, and biochemical, anthropometric and haematological indicators of health and nutritional status were measured before intervention and at three-monthly intervals during the intervention year. Following intervention, there was a significant decrease in dietary intake of sugar and saturated fat, an increase in micronutrient density, corresponding improvements in biochemical indices (for example, a 12 per cent decrease in mean serum cholesterol, increases in serum and red cell folate, serum vitamin B6 and plasma ascorbic acid), decrease in mean systolic and diastolic blood pressures, a normalisation of body mass index, and a normalisation of haematologic indices. The success of this project demonstrates that Aboriginal communities can bring about improvements in their generally poor nutritional status, and that the store-turnover method provides a valid, inexpensive and noninvasive method for evaluating the resultant changes in community diet. Although the project was undoubtedly effective in the short term, further work is in progress to assess individual strategies with respect to sustainability, cost-effectiveness and generalisability.     

Rapid-staged strategy for concomitant critical carotid and left main coronary disease with left ventricular dysfunction: IABP use

Fascicle length, pennation angle, and tendon elongation of the human tibialis anterior were measured in vivo by ultrasonography. Subjects (n = 9) were requested to develop isometric dorsiflexion torque gradually up to maximal at the ankle joint angle of 20 degrees plantarflexion from the anatomic position. Fascicle length shortened from 90 +/- 7 to 76 +/- 7 (SE) mm, pennation angle increased from 10 +/- 1 to 12 +/- 1 degrees, and tendon elongation increased up to 15 +/- 2 mm with graded force development up to maximum. The tendon stiffness increased with increasing tendon force from 10 N/mm at 0-20 N to 32 N/mm at 240-260 N. Young's modulus increased from 157 MPa at 0-20 N to 530 MPa at 240-260 N. It can be concluded that, in isometric contractions of a human muscle, mechanical work, some of which is absorbed by the tendinous tissue, is generated by the shortening of muscle fibers and that ultrasonography can be used to determine the stiffness and Young's modulus for human tendons.