Na+ channel modulation and force-frequency relationship in human myocardium

Insect cell lines in culture are used for a variety of studies. In this laboratory imaginal disc cell lines have been established from primary cultures from third instar larvae, and used for a number of experiments. The effect of ageing on the morphology and physiology of Drosophila cell lines has received very little attention, although problems of genotypic or phenotypic changes in cell lines with age are recognized in other areas of animal cell culture. We tested our cell line Cl8+ for any difference in growth, morphology and response to 20-hydroxyecdysone (20HE) at different ages (passage numbers). The cells were found to multiply faster, adhere less firmly to the substrate and to lose the tendency to aggregate at higher passages. The response to 20HE in terms of cell numbers and induction of beta-galactosidase was similar at all passage numbers but morphological changes in hormone-treated cells were less obvious in the higher passages. Cell lines are likely to vary in the extent of ageing effects but workers are advised to be aware of the possibilities. We suggest the effects of age on cell lines should be established, and passage numbers noted in experimental reports.     

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene.     

The small GTP-binding protein Rho1 is a multifunctional protein that regulates actin localization, cell polarity, and septum formation in the fission yeast Schizosaccharomyces pombe

BACKGROUND: The small GTP-binding protein Rho has been shown to regulate the formation of the actin cytoskeleton in animal cells. We have previously isolated two rho genes, rho1+ and rho2+, from the fission yeast Schizosaccharomyces pombe in order to investigate the function of Rho using genetic techniques. In this paper, we report the cellular function of Rho1. RESULTS: We found that Rho1 is essential for cell viability and cell polarity using gene disruption and by exogenous expression of botulinum C3 ADP-ribosyltransferase. In cells expressing either a constitutively active Rho1 or a dominant-negative Rho1, actin patches were delocalized. Both the cell wall and secondary septum were thick and stratified in cells expressing the constitutively active Rho1, while the cell wall of cells expressing the dominant-negative Rho1 seemed to be loosely organized. Furthermore, inactivation of Rho1 is apparently required for the separation of daughter cells. Cell fractionation studies suggested that Rho1 is predominantly membrane-bound. Moreover, we observed that Rho1 is localized to the cell periphery and to the septum. CONCLUSIONS: Rho1 is involved in actin patch localization, the control of cell polarity, the regulation of septation, and cell wall synthesis.     

Development of a geographical information system and its application to Escherichia coli O-157 patient distribution

The so called Geographical Information System (GIS) is one of the basic tools for wide range of public health applications. We had developed a general purpose GIS and applied it to represent geographical distribution of patients of the bacterium E. coli O-157 which bursted out in Japan last early summer particularly at Sakai City in Osaka Prefecture. The patient record have been supplied from the Food Safety Office of the Ministry of Health and Welfare. These records were handled by EXCEL. The basic geographical data was constructed from the map data provided by Japan Geographical Survey Institute, and ArcView 2 was used as the map system. The maps were converted to Graphics Interchange Format (GIF) files and put on our Web server.     

Peripheral nerve stimulation by time-varying magnetic fields

PURPOSE: A study was performed to assess the stimulation threshold for healthy adults using sinusoidally oscillating gradients. METHOD: One hundred thirteen healthy adults were examined in the study. ECG and physiological parameters were measured. All measurements were performed of both the head and the abdomen. The subjects were measured in the supine position with the region of interest positioned in the center of the gradient coils. The measurement was performed for three orthogonal, four oblique, and double oblique orientations. RESULTS: No volunteer reported painful, severe stimulation. The mean thresholds for peripheral stimulation in head and body measurement were similar: 85.5% of stimulation during examination of the head and 87.6% during measurements of the abdomen were reported when the y-gradient was used. CONCLUSION: The greatest frequency of reported stimulations occurs when the y-gradient is used. This was confirmed by the results and supports the hypothesis that orthogonal to the y-axis the body has its largest conductive loop, resulting in the strongest peripheral stimulation.     

A novel method for elimination of line-current harmonics insingle-stage PFC switching regulators

This paper studies a particular single-stage power-factor-correction (PFC) switching regulator employing a discontinuous-conduction-mode (DCM) boost-input cell and a continuous-current-mode (CCM) forward output cell. Although this single-stage PFC regulator can provide a reasonably high power factor when its PFC stage is operating in discontinuous mode, substantial reduction in line-current harmonics is possible by applying a suitable frequency-modulation scheme. This paper derives a frequency-modulation scheme and proposes a practical implementation using a simple translinear analog circuit. A quantitative analysis on the total harmonic distortion (THD) of the line current when the circuit is subject to a limited range of frequency variations is presented along with some considerations for practical design. Experimental data obtained from a prototype confirms the effectiveness of the proposed frequency-modulation scheme. The proposed analog translinear circuit allows custom integrated circuit implementation, making it a viable low-cost solution to the elimination of line-current harmonics in switching regulators     

Hyperhomocysteinemia: detection, risk assessment, and treatment

OBJECTIVE: The aim of this study was to evaluate both the importance of the screening strategy and the familial aggregation characteristics of families with hypercholesterolemic children. PATIENTS AND METHODS: Ninety-one families (369 subjects) with one hypercholesterolemic child were studied. In addition to clinical and general biochemical evaluation, lipids including apo A-I and B-100 were examined. LDL was quantified under ultracentrifugation. RESULTS: Among the 91 children studied, 10 (10.99%) suffered heterozygous hypercholesterolemia, while 81 (89.01%) suffered polygenic hypercholesterolemia. Following a diet, polygenic children exhibited normal lipid parameters. In heterozygous children a decrease of 19% for total cholesterol, 19.9% for LDL-cholesterol and 16.3% for apo B were observed. When starting the study, 77.5% of the family members thought that they had normal serum lipid values. At the end of the study it was confirmed that only 28% were really normolipemic, indicating that 49.4% of the individual did not know that they were suffering dyslipemia. The study also showed that fathers exhibited the highest incidence of hypercholesterolemia (80.2%) followed by brothers (65.6%) and mothers (61.5%). Therefore, 69.4% of the individuals studied exhibited dyslipemia. CONCLUSIONS: The screening strategy allows one to diagnose a high percentage (almost 50%) of individuals suffering hypercholesterolemia in families with a child previously diagnosed of this pathology. Moreover, in these families there is a high degree of familiar aggregation of dyslipemia.     

Increased expression of peripheral benzodiazepine receptors in the facial nucleus following motor neuron axotomy

Peripheral benzodiazepine receptors (PBRs) are expressed in a variety of tissues but are normally found at low levels in the brain. Following various types of nerve injury, a reactive gliosis results that exhibits a high expression of this receptor. To further characterize the expression of PBRs following neuronal injury, we evaluated PBR expression in the facial nucleus following facial nerve axotomy (FNA). Injury to a peripheral nerve results in a complex series of metabolic and morphological changes around the injured neuron. Transections of the facial nerve results in a rapid activation of both astrocytes and microglia around axotomized motor neurons. FNA resulted in an increase in the staining for both astrocytes (glial fibrillary acidic protein) and activated microglia (OX42). There was also a reduction in synaptic contacts with the motor nucleus as evidenced by reduced staining for the synaptic marker, synaptophysin. In sections labeled with [3H]-PK11195, the subsequent autoradiograms displayed marked increases in the labeling for PBRs. This increase was observed at 5, 7 and 10 days after nerve transection. The increase was primarily in the level of expression (Bmax), with no change in the affinity of the ligand (Kd). The increase in PBR expression after FNA supports the hypothesis that PBRs can be used as a sensitive marker for CNS injury.     

Worksite characteristics and changes in worksite tobacco-control initiatives. Results from the COMMIT study

Few studies have prospectively examined the characteristics associated with worksite adoption of tobacco-control initiatives. Data were collected as part of the Community Intervention Trial (COMMIT) for Smoking Cessation, which conducted interventions in 11 communities. This smoking cessation intervention was based on community organization principles and delivered through multiple community channels, including worksites, health care providers, the media, and cessation resources. This article reports results from telephone interviews of intervention community worksites having 50 or more employees, conducted at baseline and the end of the intervention period. Among worksites that responded to both baseline and final surveys, 83% had not adopted a smoke-free policy at baseline, and 61% did not offer any cessation aid or quitting resources at baseline. By the final survey, 34% of those with no smoking ban at baseline had become smoke-free, and 36% of those offering no cessation assistance at baseline were offering cessation resources at the follow-up. The prevalence of policy adoption was higher among worksites employing more female employees and offering other health-promotion activities; manufacturing businesses were significantly less likely than businesses other than service and wholesale/retail businesses to adopt policies. Adoption of cessation programs was significantly more likely among worksites employing 100 to 249 workers, compared with those employing 50 to 99 workers; those predominantly employing men; those offering other types of health-promotion activities; and those with a higher rate of turnover. These results provide important information about the characteristics of worksites likely to engage in tobacco-control efforts. Health educators and others may choose to target those worksites most ready for adoption of tobacco control policies and programs, as indicated by these findings.