Retinal accumulation of the phosducin/T beta gamma and transducin complexes in developing normal mice and in mice and dogs with inherited retinal degeneration

Rod photoreceptors of mammalian retinas contain a 33-kDa phosphoprotein, phosducin, which complexes with the beta, gamma-subunits of transducin (T beta gamma). The level of phosducin phosphorylation is modulated by light, suggesting that the phosducin/T beta gamma complex has a pivotal role in light-regulated events that occur in photoreceptors. We have investigated, in developing mouse retinas, the age at which the complex is first detected and the subsequent accumulation of the phosducin/T beta gamma complex during postnatal life. Western blot analysis detected immunoreactivity both for phosducin and T beta in retinal homogenates of 3-day-old mice. Thereafter, the level of immunoreactivity for both proteins increased steadily, to reach adult levels in the next 2 postnatal weeks. Gel filtration analysis of extracts from immature mouse retina showed that phosducin and T beta co-eluted, like the phosducin/T beta gamma complex of adult retina, as a 77-kDa complex, indicating that the phosducin/T beta gamma complex is formed when photoreceptors first synthesize the components of the complex. While the levels of the phosducin/T beta gamma complex increased steadily during the first 2 postnatal weeks, the subunits of transducin complex, T alpha together with additional amounts of T beta gamma, only started to appear around the 7-9th postnatal day, and the level of transducin complex increased sharply at 11-14 days to reach adult levels that are similar to those of phosducin/T beta gamma complex.(ABSTRACT TRUNCATED AT 250 WORDS)     

A developmental study of interphotoreceptor retinoid-binding protein (IRBP) in single and double homozygous rd and rds mutant mouse retinae

Interphotoreceptor retinoid-binding protein (IRBP) was studied using immunochemical and immunocytochemical techniques in retinae of mice with allelic combinations at the rd and rds loci at different stages of development and degeneration. Until postnatal day 7 (P7), IRBP is located intracellularly in developing retinae of the different genotypes. Thereafter, IRBP is present mainly in the interphotoreceptor matrix. As previously noted, cell death is slowest in the heterozygous +/+,rds/+ mutant with loss increasing in order in +/+,rds/rds, rd/rd, rds/rds and rd/rd,+/+ animals. The IRBP content of the total retina also approximates this pattern, with lowest amounts by far in rd/rd, rds/rds and rd/rd,+/+ mutants (after P14). Interestingly though, IRBP loss significantly precedes visual cell loss in the rd/rd,rds/rds retina. In all the mutants, the remaining rod cells in the outer nuclear layer exhibit synthesis of intracellularly located IRBP at late stages of degeneration. In the single homozygous rd/rd,+/+ and the double homozygous rd/rd,rds/rds mutants, IRBP is present intracellularly during the entire degenerative process with somewhat less intracellular IRBP in the rd/rd,rds/rds mutant. Retinae of homozygous +/+,rds/rds and heterozygous +/+,rds/+ animals exhibit a normal distribution pattern of IRBP immunoreactivity until loss of photoreceptor cells becomes pronounced at later stages of the disease. Many of the remaining cells at this time are probably cone elements although they are structurally changed. Double labeling with IRBP and S-antigen demonstrates, in many but not all, the presence of both proteins in the same cell body. Immunocytochemistry clearly demonstrated the presence of IRBP in remaining photoreceptor cells at late stages of the disease. Thus, the biochemically measured loss of IRBP appears to be a complex process neither directly dependent on the loss of photoreceptor outer segments and reduced interphotoreceptor matrix space (e.g. there is a sustained IRBP level in rodless rds mutants) nor simply due to cell death (e.g. in the rd/rd,rds/rds mutant, IRBP loss significantly precedes cell loss). That this IRBP is mainly intracellular, however, may indicate an abnormality in secretion which, combined with other factors, induces a degenerated and less differentiated phenotype.     

Diurnal variation in peak expiratory flow rate among workers exposed to toluene diisocyanate in the polyurethane foam manufacturing industry.

The diurnal variation in peak expiratory flow rate (PEFR) was studied in 26 mixers from eight factories making polyurethane foam, who were exposed to toluene diisocyanate (TDI), and 26 unexposed controls matched for age, race, and smoking. They were all men. The mean diurnal variation in PEFR of the mixers was 6.2%, which was significantly higher than the 4.3% for controls. Six mixers had a diurnal variation of greater than 15% on at least one day compared with none among the controls. There was, however, no overt cause of occupational asthma. All but one of the 24 environmental samples taken exceeded the short term exposure limit of 0.02 ppm for TDI. This accounted for the high prevalence (50%) of irritative symptoms such as cough and eye irritation. Forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) (%) was negatively correlated with duration of exposure to TDI. Foam workers may still have high exposure to TDI, high prevalence of irritative symptoms, increased diurnal variation in PEFR and evidence of chronic airway obstruction, particularly in those with greater than or equal to 10 years of exposure.     

Chlorella virus PBCV-1 replication is not affected by cytoskeletal disruptors.

The majority, if not the entire life cycle, of the large dsDNA-containing algal virus PBCV-1 occurs in localized regions in the cytoplasm. Thirteen drugs that disrupt the cytoskeleton had no effect on PBCV-1 replication at concentrations which inhibited host growth. Therefore, host cytoskeletal elements do not appear to be important in PBCV-1 morphogenesis.     

Ligase chain reaction for diagnosis of familial hypertrophic cardiomyopathy

ＬｉｇａｓｅｃｈａｉｎｒｅａｃｔｉｏｎｆｏｒｄｉａｇｎｏｓｉｓｏｆｆａｍｉｌｉａｌｈｙｐｅｒｔｒｏｐｈｉｃｃａｒｄｉｏｍｙｏｐａｔｈｙＳｕｎＷｅｉｄｏｎｇ孙维东，ＨａｎｓｅｌＳｔｅｄｍａｎ，ＣｈｅｎＸｉａｏｌｉ，ＷｅｉＹｕ，ＬｉｕＭｅｉｚｈｅｎ，Ｘｕ...     

A feasibility study on teaching evaluation system in medical education

The purpose of this study is to develop an evaluation instrument with high feasibility and acceptability, and to quantify the outcome of evaluation, in order to set up an efficient evaluation system. Teaching evaluation with questionnaire by students has been carried out in National Yang-Ming Medical College for two years. With the support of both teachers and students, the system has been established and conducted on a regular basis. The most important purpose of evaluation is to improve the quality of teaching. During the two academic years (Sep. 1986-June 1988) of the program, the overall response rate was 44.5%, the Department of Nursing had the highest response rate, followed by Dentistry, Medicine-Post Graduate, Medical Technology, and Medicine. Taking into consideration of the year and the class size, the regression analysis found that higher year or smaller size of the class had better response rate. The response rates dropped significantly after the first academic year regardless of department or year. A total of 23 classes were included in the evaluation program and 99 courses were evaluated. All questions in the questionnaire used a 0 to 4 ordinal scale, in which 0 (improvement needed) was the low end and 4 (excellent) the high end. The mean score of the seven questions of teaching evaluation was 2.47. As a whole, the students were satisfied with the teaching. As to the categories of courses, clinical courses had better mean score than basic medical courses, and basic medical courses had better mean score than common required courses. To evaluate the effectiveness of the teaching, students' achievement was used as the outcome variable. The most important predictive variable was the method of instruction, followed by the content of lecture such as degree of difficulty of the lecture and cognitiveness of the contents. The above 3 variables explained 76% of the variation of the students' achievement. However, the significant of teachers' speech, performance and attitude were not so influential. Analysis based on the characteristics of the teachers (sex, age, position, and teaching experience), the characteristics of students (department and year), teaching environments (time and place), and the 3 categories of courses (clinical, basic medical and common required courses) showed that all the above variables only explained less then 10% of the variation of the students' achievement.     

Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities

To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N-nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine-deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level.     

Reduction mammaplasty by central pedicle flap with short submammary scar

Reduction mammaplasty was performed in 30 patients by combining the central pedicle flap method with the short submammary scar (3-S) technique to avoid the common drawbacks of currently popular dermoglandular procedures. Reduction was accomplished by using perforating vascular branches from the pectoralis major muscle and its fascia supplying the nipple and breast parenchyme instead of the subdermal plexus. The central vascular pedicle supplying the nipple-areola complex was preserved. Only the periphery of the breast parenchyme was resected circumferentially, with the exception of the inferolateral portion, so as not to injure the sensory nerve. The remaining breast parenchyme was preserved in an inverted cone shape. The nipple-areola complex was safely transposed with great freedom, and the amount of resection was accurately adjusted for symmetry. No cases of nipple-areola complex sensory change occurred postoperatively, and lactation is possible because of preservation of the lactiferous ducts. The length of postoperative scars was reduced by using the short submammary scar technique. We believe this combined method is ideal in patients requiring resections ranging from 200 to 600 g per breast with good skin elasticity and moderate degree of ptosis.Presented at the Sixth Asian Pacific Congress of the International Confederation for Plastic and Reconstructive Surgery, in Seoul, Korea, October 1993.