Correlation with larval body size of mRNA levels of growth hormone, growth hormone receptor I and insulin-like growth factor I in larval torafugu Takifugu rubripes.

The full-length of insulin-like growth factor (IGF) complementary (c)DNAs encoded by igf-I and igf-II from torafugu pufferfish Takifugu rubripes were cloned in the present study. The deduced amino acid sequences of the two genes showed c. 80% identity each with those of Igf-I and Igf-II from other teleosts, respectively. Two growth hormone (GH) receptors, ghr1 and ghr2, were also cloned in silico using the T. rubripes Fugu genome database. The transcripts of T. rubripes igf-I were detected in slow muscle, heart, skin, gill, liver and intestine but not in fast muscle, spleen and testis of adult fish, whereas those of igf-II were found in all tissues examined. Subsequently, the accumulated messenger (m)RNA levels of igf-I and igf-II were investigated in an F(2) population derived from a male of an apparent fast-growing T. rubripes strain and a wild female T. rubripes together with those of other growth-related genes encoding Gh, Ghr1 and Ghr2, and with those of prolactin (Prl) and leptin (Lep) previously reported. The accumulated mRNA levels of igf-I, gh and ghr1 were significantly correlated to growth rate at larval stages in the population, but not for those of igf-II, prl, ghr2 and lep. Although it is unclear whether or not this phenotype is directly related to the heredity of the fast-growing strain, the findings suggest that the expression of igf-I, gh and ghr1 is involved in the regulation of growth rate at larval stages in T. rubripes.

Pallidal high-frequency deep brain stimulation for camptocormia: an experience of three cases.

INTRODUCTION: The term "camptocormia" describes a forward-flexed posture. It is a condition characterized by severe frontal flexion of the trunk. Recently, camptocormia has been regarded as a form of abdominal segmental dystonia. Deep brain stimulation (DBS) is a promising therapeutic approach to various types of movement disorders. The authors report the neurological effects of DBS to the bilateral globus pallidum (GPi) in three cases of disabling camptocormia. METHODS: Of the 36 patients with dystonia, three had symptoms similar to that of camptocormia, and all of these patients underwent GPi-DBS. The site of DBS electrode placement was verified by magnetic resonance imaging (MRI). The Burke Fahn and Marsden dystonia rating scale (BFMDRS) was employed to evaluate the severity of dystonic symptoms preoperatively and postoperatively. RESULTS: Significant functional improvement following GPi-DBS was noted in the majority of dystonia cases. At a follow-up observation after more than six months, the overall improvement rate was 71.2 +/- 27.0%, in all dystonia cases who underwent the GPi-DBS. In contrast, the improvement rate of the three camptocormia cases was 92.2 +/- 5.3%. It was confirmed that the improvement rate for camptocormia was much higher than for other types of dystonia. CONCLUSION: According to our experience, a patient with a forward-bent dystonic posture indicative of camptocormia is a good candidate for GPi-DBS. The findings of this study add further support to GPi-DBS as an effective treatment for dystonia, and provide the information on predictors of a good outcome.

Carcinogenicity study of gamma-oryzanol in F344 rats.

The carcinogenic potential of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, was studied in F344 rats. Groups of 50 males and 50 females were fed a diet containing 0 (control), 200, 600 or 2000 mg gamma-oryzanol/kg body weight/day for 2 yr. Although females in the highest dose group (2000 mg/kg body weight) showed a slight decrease in body weight at 104 wk, there were no treatment-related changes in general condition, food consumption, mortality, organ weight or haematology. Histopathological examination showed various tumours in all groups, including the control group. In the control and 2000-mg/kg groups, high tumour incidences were observed in the testes, pituitary and thyroid of males, and in the pituitary, uterus and mammary gland of females; however, there was no significant increase in the incidence of any tumours between the control and the 2000-mg/kg groups. The findings indicate that under the experimental conditions described gamma-oryzanol was not carcinogenic in F344 rats.

Carcinogenicity study of gamma-oryzanol in B6C3F1 mice.

The carcinogenic potential of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, was studied in B6C3F1 mice. Groups of 50 males and 50 females were fed a diet containing 0 (control), 200, 600 or 2000 mg gamma-oryzanol/kg body weight/day for 78 wk. No treatment-related changes were observed in general condition, body weight, food consumption, mortality, organ weight or haematology. Histopathological examinations showed various tumours in all groups, including the control group. In the control and 2000-mg/kg groups, relatively high tumour incidences were observed in the liver of males and in the haematopoietic organs of females. However, there was no statistically significant difference in the incidence of any tumours between the control and the 2000-mg/kg groups. The findings indicate that under the experimental conditions described gamma-oryzanol was not carcinogenic in B6C3F1 mice.

Paroxysmal kinesigenic choreoathetosis with abnormal electroencephalogram during attacks.

An 18-year-old man with paroxysmal kinesigenic choreoathetosis (PKC) showed rhythmic electroencephalographic (EEG) discharges of 5-Hz spikes over the entire scalp during episodes. The EEG findings in this case suggest that PKC may have an epileptogenic basis.

An epidemiological study on diabetes mellitus in the Iwaki area.

We made a statistical study of diabetics in the medical ward of Iwaki Kyoritsu General Hospital over a period of 30 years. The number of diabetic inpatients at our hospital was 24 in 1951, 152 in 1970 and 350 in 1980. The ratio of diabetic inpatients to the total number of inpatients at the medical department of our hospital increased from 2 percent in 1957 to 15 percent in 1980. According to reports from the Welfare Ministry of Japan on the nutritional intake of the Japanese, calorie intake has not changed, but there has been a change in composition. Carbohydrate intake has decreased, and animal protein and fat intakes have increased. Therefore, the increase in the number of diabetic inpatients in the medical ward of our hospital seems to be connected to the changes in diet; i.e., the increases in the intake of animal protein and fat. As causes of death in diabetics, malignant neoplasms, cerebrovascular diseases and renal diseases were most prevalent. In primary diabetics, cerebrovascular disease, malignant neoplasms and renal diseases were responsible for the greater percentage, and in secondary diabetics, liver cirrhoses and malignant neoplasms were responsible for the greater percentage. In primary diabetics, renal diseases has shown a remarkable increase with time.

Mode of action of bottromycin A2: effect of bottromycin A2 on polysomes.

When bottromycin A2 was added to an in vitro protein synthesis system carried out by naturally occurring polysomes, it inhibited protein synthesis effectively. Examination of the 3 steps of peptide chain elongation revealed that the binding of aminoacyl-tRNA to the polyribosomes was inhibited by bottromycin A2. In contrast, we concluded that the peptide bond formation and the translocation steps in this system were not inhibited by bottromycin A2 on the basis of the following observations: (1) The break-down of polysomes, which is dependent on EFG, puromycin and RR (ribosome releasing) factor, was insensitive to bottromycin A2; (2) The puromycin dependent release of polypeptide from polysomes, with or without EFG, was not inhibited by bottromycin A2. Thus bottromycin specifically interferes with proper functioning of the A sites of polysomes. This is consistent with the results obtained using the model system with synthetic polynucleotides.

Mode of action of bottromycin A2. Release of aminoacyl- or peptidyl-tRNA from ribosomes.

Bottromycin A2 inhibited MS2 phage RNA-dependent protein synthesis as well as polyuridylic acid-(poly(U))- or polyadenylic acid (poly(A))-dependent polypeptide synthesis. When the ribosomal complex with N-acetyl-[14C]phenylalanyl-tRNA (N-acetyl-[14C]Phe-tRNA) at the A site was subjected to bottromycin A2, the release of N-acetyl-[14C]Phe-tRNA was observed while no release of N-acetyl-[14C]Phe-tRNA from the donor site was observed, indicating that the action of bottromycin A2 is specific to the A site of ribosomes. Due to bottromycin's capacity to release [14C]Phe-tRNA or N-acetyl-[14C]Phe-tRNA from the ribosomal acceptor site (A site), bottromycin A2 inhibited the nonenzymatic binding of N-acetyl-[14C]Phe-tRNA and elongation factor T (EF-T)-dependent binding if the concentration of EF-Tu-GTP-[14C]Phe-tRNA ternary complex was low. Our data are consistent with the possibility that the inhibition of overall polypeptide synthesis by bottromycin A2 is at least partly due to bottromycin A2's activity to release aminoacyl- or oligopeptidyl-tRNA from ribosomes. Among 10 antibiotics tested, bottromycin A2 and lincomycin released aminoacyl-tRNA from ribosomes.

Release of (oligo) peptidyl-tRNA from ribosomes by erythromycin A.

Erythromycin A released peptidyl-tRNA in the in vitro polypeptide synthesis system with bacterial components programmed by synthetic polynucleotide. This is consistent with our hypothesis that erythromycin A inhibits translocation by preventing proper situation of oligopeptidyl-tRNA in the donor (D) site on ribosomes.