Genetic control of differential baseline breathing pattern

The purpose of the present study was to determine the genetic control of baseline breathing pattern by examining the mode of inheritance between two inbred murine strains with differential breathing characteristics. Specifically, the rapid, shallow phenotype of the C57BL/6J (B6) strain is consistently distinct from the slow, deep phenotype of the C3H/HeJ (C3) strain. The response distributions of segregant and nonsegregant progeny were compared with the two progenitor strains to determine the mode of inheritance for each ventilatory characteristic. The BXH recombinant inbred (RI) strains derived from the B6 and C3 progenitors were examined to establish strain distribution patterns for each ventilatory trait. To establish the mode of inheritance, baseline breathing frequency (f), tidal volume, and inspiratory time (TI) were measured five times in each of 178 mature male animals from the two progenitor strains and their progeny by using whole body plethysmography. With respect to f and TI, the two progenitor strains were consistently distinct, and segregation analyses of the inheritance pattern suggest that the most parsimonious genetic model for response distributions of f and TI is a two-loci model. In similar experiments conducted on 82 mature male animals from 12 BXH RI strains, each parental phenotype was represented by one or more of the RI strains. Intermediate phenotypes emerged to confirm the likelihood that parental strain differences in f and TI were determined by more than one locus. Taken together, these studies suggest that the phenotypic difference in baseline respiratory timing between male B6 and C3 mice is best explained by a genetic model that considers at least two loci as major determinants.     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

The merits of varicella vaccination for varicella non-immune health care workers

Immunity against varicella can be reliably established by history and, if negative, confirmed or refuted by serology. If non-immune, the merits of varicella vaccine for a health care worker (HCW) can be stated clearly: Protection from a disease which may be particularly severe in an adult, and evading the inconvenience (investigation time and possible work restriction) and cost of managing an exposure. This paper discusses implementation of a varicella immunity program for HCWs at Columbia Presbyterian Hospital in Oklahoma City.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Tay-Sachs disease in persons of French-Canadian heritage in northern New England

This study sought to determine whether persons of French-Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay-Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay-Sachs deaths in a cohort of 372,000 live births between 1977-1986. The proportion of the total population with French-Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay-Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay-Sachs disease. In 41,000 births, both parents were of French-Canadian heritage, and in an additional 93,000 births, one parent was of French-Canadian heritage. No cases of Tay-Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8-20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay-Sachs disease heterozygosity is not indicated for persons of French-Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French-Canadian heritage residing in other states. Further studies of Tay-Sachs disease mutations and prevalence among persons of French-Canadian heritage will be important to determine possible regional variations in gene frequencies.     

Application of the T-integral and S criteria in finite element analysis of impact damage at fastener holes in graphite/epoxy laminates under compression

This paper illustrates the application of two fracture criteria, Atluri's T^*-integral and Sih's strain energy density factor S for estimating the residual strength of an impact damaged fastener hole in a composite laminate. Finite element analyses are performed, and the magnitude and distribution of T^* and S are determined around the delamination. It is found that the profiles of these distributions are extremely complex and sensitive to the modelling of the stress fields close to the delamination. The effects of local closure, shear moduli and cracktip singularity are investigated. It is also shown that the representation of the stress singularity in the finite element model has a strong effect on the distribution of T^* and S. The distribution of both T^* and S is such that three local maxima occur and are situated at the same locations around the delamination. These locations approximately coincide with the points of maximum growth as revealed by ultrasonic C-scan of the damage growth of several specimens. The T^*-integral is shown to be more sensitive to the values of interlaminar shear moduli than S. The results of the analyses suggest that both the T^*-integral and S criteria may be successfully employed in the prediction of residual strength. However, S is better at predicting the direction of damage growth provided the stress fields near the delamination can be accurately modelled.     

A strain hardening failure assessment diagram derived from carbon-manganese steel compact tension specimens

A failure assessment diagram is derived from carbon-manganese steel compact tension specimens. The diagram has been determined from an elastic-plastic finite element analysis of a compact tension specimen geometry. The diagram has been validated by using experimental fracture toughness data obtained on the same steel and specimen geometry modelled in the finite element analysis. The plastic collapse load has been determined empirically for this geometry.It is shown that a non-work-hardening failure assessment diagram is not a good representation of the experimental data and that the computed failure assessment diagram is more appropriate for describing the behaviour of the carbon-manganese steel specimens.     

Increased analytical precision in the hollow cathode discharge emission source by improved discharge current control.

A significant improvement in the precision of the hollow cathode as an emission source is reported. Precision of 1% or less has been observed several times over periods of several hours. An average long-term stability of 4.3% for Ll and 6.0% for Na in the emission signal from microsamples (less than 50 nL) deposited in the hollow cathode discharge source is reported. The improved precision is attributed primarily to the introduction of electronics that hold the discharge current more nearly constant and to the shielding of all wiring to the source from the power supply. A current-controlled switch that is capable of driving a hollow cathode discharge in either dc or pulsed mode is described. This switch is capable of generating current pulses as short as 2 microseconds through a resistive load and greatly improves the discharge stability and repeatability at turn-on in both the dc and pulsed modes. The characteristics of pulses produced by this switch are presented; however, analytical performance is reported only for the dc mode. Temporal current plots are presented for the new instrumentation and compared to plots taken with commonly used current-controlled power supplies. Instrumentation, operation, and sample preparation procedures are described. Typical temporal profiles of the emission signal from microsamples deposited in AI and stainless steel hollow cathodes are given.     

Protein phosphorylation: technologies for the identification of phosphoamino acids

Protein phosphorylation plays a central role in many biological and biomedical phenomena. In this review, while a brief overview of the occurrence and function of protein phosphorylation is given, the primary focus is on studies related to the detection and analysis of phosphorylation both in vivo and in vitro. We focus on phosphorylation of serine, threonine and tyrosine, the most commonly phosphorylated amino acids in eukaryotes. Technologies such as radiolabelling, antibody recognition, chromatographic methods (HPLC, TLC), electrophoresis, Edman sequencing and mass spectrometry are reviewed. We consider the speed, simplicity and sensitivity of tools for detection and identification of protein phosphorylation, as well as quantitation and site characterisation. The limitations of currently available methods are summarised.