CMOS-based smart-electrode-type retinal stimulator with bullet-shaped bulk Pt electrodes.

A CMOS-based flexible retinal stimulator equipped with bullet-shaped bulk Pt electrodes was fabricated and demonstrated. We designed a new CMOS unit chip with an on-chip stimulator, single- and multi-site stimulation modes, and monitoring functions. We have developed a new structure and packaging process of flexible retinal stimulator with bullet-type bulk Pt electrode. We have confirmed the retinal stimulation functionality in an in vivo stimulation trial on rabbit's retina.

Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator.

We implemented a light-sensing function on CMOS-based multi-chip stimulator for retinal prosthesis. Using the light-sensing circuitry attached to each stimulation electrode, the flexible multi-chip stimulator is capable of image-based patterned stimulation. We verified the function of the light-controlled decision based on the light intensity measured just beside the stimulation site. We also experimentally demonstrated in vivo retinal stimulation on rabbit's retina with light-controlled decision. The result of the present work is a simplified demonstration for the concept of retinal prosthesis with on-site imaging.

Effects of phosphorus contents on the gelatinization and retrogradation of potato starch.

Effects of phosphorus content (510 to 987 ppm) on the gelatinization and retrogradation of 6 potato cultivars (Benimaru, Hokkaikogane, Irish Cobbler, Konafubuki, Sakurafubuki, and Touya) were studied. Pasting properties were analyzed by RVA, thermal properties by DSC, and mechanical properties of the starch gels by TA. Phosphorus was positively correlated with swelling power (r= 0.84) and negatively correlated with solubility (r= 0.83). Phosphorus content showed significant effect on certain pasting properties of potato starch such as peak viscosity, breakdown, and setback. Phosphorus content showed a significant positive correlation with peak viscosity (r= 0.95) and breakdown (r= 0.90). Increasing concentration of phosphorus tends to decrease the setback. Phosphorus content had no influence on thermal properties and mechanical properties of potato starch gel.

Effect of the central nervous system on mucosal growth and apoptosis in the small intestine.

Recently our studies have demonstrated that the central nervous system regulates in part mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase (ODC) activity is a key enzyme for polyamine synthesis which plays an important role for the intestinal mucosal growth. We have demonstrated that the increase of ODC activity in the duodenum just before the dark period is abolished by truncal vagotomy and that the infusion of 2-deoxy-D-glucose into the third cerebroventricle activates ODC activity in the small intestine. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. Our preliminary data showed that intestinal mucosal apoptosis decreased in the ventromedial-hypothalamus-lesioned rat. These results indicate that the central nervous system, in addition to local factors, is related to regulation of mucosal homeostasis in the intestinal mucosa.

[Efficacy of stress management classes at a health center].

Although interest in mental health promotion has recently been increasing, the most appropriate approaches remain to be determined. Therefore we conducted Stress Management Classes (SMCs) at Higashi Osaka City Naka Health Center in an attempt to help residents to improve their mental health. The purpose of this study was to evaluate the efficacy of SMCs, held four times over 2 months, with an educational program including the concept of stress and instruction in autogenic training as a relaxation technique. Subjects who attended a Health Promotion Class (HPC) at Osaka Prefectural Kaizuka Health Center were used as controls for the study. The aim of the HPC was to prevent chronic physical diseases such as hypertension, diabetes, and hyperlipidemia, with the program consisting mainly of exercise once a week for 3 months. The results were as follows: 1) People who attended SMCs were more likely to have mental health problems than those who attended the HPC. As a result, mentally ill patients could be diagnosed and receive psychiatric treatment at an early stage in the SMC group. 2) Both SMC and HPC attenders reported improvement of their mental health status with the use of POMS (Profile of Mood States). 3) Both SMC and HPC attenders exhibited significant decrease of blood pressure. Although attenders of both classes improved their mental health status, it is important to be able to attract individuals who are in a poor mental condition in case of mental health promotion. In this trial, we found that the term "stress management" was very useful because people who suffered stress were likely to be interested in it. After the Community Health Law was established in 1994, the flow of community health activities has been shifting from the prefectural government to the municipality. However, promoting mental health and welfare is still mainly the role of the prefectural government. In this sense, health centers are appropriate institutions to hold classes as in this trial.

Molecular cloning, localization, and developmental expression of mouse brain finger protein (Bfp)/ZNF179: distribution of bfp mRNA partially coincides with the affected areas of Smith-Magenis syndrome.

Bfp (brain finger protein) is a member of the RING finger protein family, which is highly expressed in the brain. We have previously shown that one copy of the human bfp gene, mapped at 17p11.2, was actually deleted in six of six Smith-Magenis syndrome (SMS) patients. Now we have isolated the mouse bfp cDNA. Using in situ hybridization and immunohistochemistry, the distribution of mouse bfp mRNA and protein was identified especially in neural cells of the cerebral cortex, hippocampus, lateral amygdaloid nucleus, and ventromedial hypothalamus. In primary culture of the whole brain in a neonatal mouse, the Bfp protein was detected in both neuron and glial cells, and its subcellular localization was predominantly in the nucleus, but some amounts were also found in the cytoplasm. The bfp mRNA was also expressed strongly in the marginal zone of brain vesicles, optic stalk, and cartilage primordium, which are part of the critical tissues frequently involved in SMS patients, and in such tissues as nasal epithelium and primordium of follicles in a 13. 5-dpc embryo. Subsequently, its amount in the developing brain further increased during embryogenesis, reaching the highest level in the adult brain. These findings suggest a possibility that Bfp might be involved in the pathogenesis of Smith-Magenis syndrome as a regulator protein related to neural differentiation and function.

[A case of cutaneous pseudallescheriosis resembling sporotrichosis].

An 83-year-old man with aplastic anemia and steroid induced diabetes mellitus developed multiple nodules with pus on the back of his right hand and forearm. He had been treated with a daily dose of 30mg prednisolone for 2 months. These lesions had appeared a month before his visit. The histopathological findings revealed dermal abscesses containing hyphal structures, lymphocytes, histiocytes and giant cells. Grocott-Methenamine stain demonstrated abundant fungal elements. In culture, colonies grow rapidly and produce a white, cottony mycelium which later becomes gray in color. Microscopically, ovoid and pyriform conidia are produced at the ends of long slender conidiophores. On PCA agar, synnemata with small conidal heads developed at 37 degrees C but cleistothecia did not appear. The patient did not respond to itraconazole therapy, however, with hyperthermic treatment, the eruptions gradually healed. Based on these findings, this fungal infection was diagnosed as pseudallescheriosis.

[Transurethral microwave thermotherapy for benign prostatic hyperplasia].

BACKGROUND: We studied the clinical efficacy of transurethral microwave thermotherapy (TUMT) using Endotherm UMW system (OLYMPUS). METHODS: TUMT was performed in 28 patients with benign prostatic hyperplasia (BPH). Three patients of them were catheterized because of urinary retention. The treatment was performed in a single session for an hour. The urethral surface temperature was set at 39 degrees C, and the coolant flow of the urethral applicator (21 Fr balloon catheter) was set at 30 ml/min, to heat up the broad area of the prostate up to 45 degrees C. The clinical efficacy was evaluated by analyzing subjective responses, using the International Prostate Symptom Score (I-PSS) scale (S) and QOL score (L), and objective responses, using peak urinary flow rate (Qmax), average flow rate (Qave), residual urine volume and prostate volume following the treatment. RESULTS: At 24 weeks after the treatment, significant improvement were observed in S score (41%), L score (37%), Qmax (53%) and Qave (62%). Although there was no significant decrease in residual urine and prostate volume. The three patients, with a catheter indwelled because of urinary retention, were all free of the catheter within 4 weeks after the treatment. During and after the treatment, no severe adverse effects, including transient urinary retention needed for indwelling a catheter, was detected. CONCLUSION: A single session of TUMT by Endotherm UMW considered to be safe and useful for symptomatic BPH patients, even who are not indicated for transurethral resection of the prostate (TUR-P) because of underlying disorders.

A novel genetic system to isolate a dominant negative effector on DNA-binding activity of Oct-2.

Recent studies have revealed that interactions between transcription factors play an important role in regulation of gene expression in eukaryotic cells. To isolate cDNA clones that dominantly inhibit the DNA-binding activity of Oct-2, chosen as a representative factor, we have developed a novel screening system. This employs an Escherichia coli tester strain carrying a modified lac operon as a reporter gene, with the lac operator sequence replaced by an octamer sequence. Oct-2 expressed in this tester strain represses the expression of the reporter gene and changes the phenotype of the cell from Lac+to Lac-. Introduction of a cDNA expression library prepared from a human T-cell line into the Oct-2-harboring tester strain allowed selection of three Lac+clones out of 1 x 10(5) transformants. One of them, hT86, encoding a putative zinc finger protein was found to derepress beta-galactosidase activity in the Oct-2-harboring tester strain at the transcriptional level. In gel mobility shift assays, hT86 attenuated the intensity of the retarded band composed of the octamer probe and Oct-2, suggesting a dominant negative effect on the DNA-binding activity of Oct-2. The strategy described here provides a new approach for studying protein-protein interactions that govern the complex regulation of gene expression.

Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.

Contraction of skeletal muscle is triggered by the release of Ca2+ from the sarcoplasmic reticulum (SR) after depolarization of transverse tubules. The ryanodine receptor exists as a 'foot' protein in the junctional gap between the sarcoplasmic reticulum and the transverse tubule in skeletal muscle, and is proposed to function as a calcium-release channel during excitation-contraction (E-C) coupling. Previous complementary DNA-cloning studies have defined three distinct subtypes of the ryanodine receptor in mammalian tissues, namely skeletal muscle, cardiac and brain types. We report here mice with a targeted mutation in the skeletal muscle ryanodine receptor gene. Mice homozygous for the mutation die perinatally with gross abnormalities of the skeletal muscle. The contractile response to electrical stimulation under physiological conditions is totally abolished in the mutant muscle, although ryanodine receptors other than the skeletal-muscle type seem to exist because the response to caffeine is retained. Our results show that the skeletal muscle ryanodine receptor is essential for both muscular maturation and E-C coupling, and also imply that the function of the skeletal muscle ryanodine receptor during E-C coupling cannot be substituted by other subtypes of the receptor.

Hepatotoxicity of gardenia yellow color in rats.

Acute toxicity by gardenia yellow color was studied in rats. Oral administration of the colorant at doses of 800 mg/kg up to 5000 mg/kg caused diarrhea and increases in serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner. After 24 h of oral treatment with 2000 mg/kg of the colorant, liver showed partially hemorrhagic changes and the intestinal tract, especially the duodenum, appeared blue. The toxicity induced by the colorant was stronger by oral administration than by intraperitoneal administration. The content of geniposide, an iridoid compound, was estimated to be 28% of the colorant, and this iridoid accounted for almost all the hepatotoxic activity of the colorant.

Sensory input to cerebellocerebral relay neurons in the cat thalamus.

Intracellular recording techniques were used to study the synaptic responses of feline ventrolateral neurons to dorsal column, spinothalamic and sensory cortex stimulation. More than 75% of the cells responded with short- and long-latency excitatory or inhibitory postsynaptic potentials to the one or/and other stimulation sites. These findings indicate that a considerable amount of somatosensory integration in the cerebellocerebral circuit occurs in the thalamic relay neurons.

A morphological investigation of thalamic neurons by intracellular HRP staining in cats.

Morphological analysis of 77 neurons in the ventroanterior (VA), ventrolateral (VL), ventromedial (VM), and central lateral (CL) nuclei was performed by intracellular HRP staining in combination with electrophysiological studies. The neurons were classified into four groups according to either electrophysiological or morphological criteria, i.e., 20 relay neurons (18 thalamocortical (T-C) and two thalamocaudate (T-Cd) relay neurons), 17 projection neurons, 36 unidentified neurons, and four presumed interneurons. All 36 unidentified neurons had morphological features similar to those of relay and projection neurons. All neurons except four presumed interneurons had dendrites sparsely covered with spinelike appendages. Most of their dendrites displayed a spherically radiating branching pattern, and a few showed a tufted or linearly oriented pattern. Sizes of somata and dendritic radii were compared in entopeduncular (Ent)-responsive (n = 25) and cerebellar (CN)-responsive groups (n = 37) in VA, VL, and VM nuclei. The soma size was similar in VL (18-21 X 29-34 micron) and VM (15-19 X 29-31 micron), but in VA, CN-responsive neurons (15 X 30 micron) seemed to be smaller than Ent-responsive ones (22 X 36 micron). The largest dendritic field of neurons in each thalamic nucleus was similar in both groups. They were about 250-320 micron in radius. Diameters of axons were also compared but no statistically significant difference was detected (i.e., 1.5 +/- 0.3 (mean +/- S.D.) micron for the Ent group and 1.7 +/- 0.5 micron for the CN group). Three types of axonal trajectories were noted, i.e., neurons projecting their axons dorsolaterally, ventrolaterally, or horizontally. Fourteen neurons out of 37 relay and projection neurons gave off several fine distal axon collaterals in the thalamic reticular nucleus, and one T-Cd, three projection, and one unidentified neurons gave off proximal axon collaterals near the soma-dendritic domain in addition to those in the thalamic reticular nucleus. Four neurons classified as presumed interneurons had smaller somata (9-13 X 18-23 micron) and varicose dendrites. Three of them received Ent-induced inhibitory postsynaptic potentials (IPSPs) or CN-induced excitatory postsynaptic potentials (EPSPs). Several presumed axon terminals were found to cover the soma of an adjacent neuron, which seemed to indicate their inhibitory nature. The proximal axon collaterals in the ventral thalamic nuclei may consist of local inhibitory circuits with presumed interneurons in addition to other inhibitory circuits with thalamic reticular neurons.

[Effect of elcatonin on experimental osteoporosis induced by ovariectomy and low calcium diet in beagles].

Effect of elcatonin, a synthesized analogue of eel calcitonin, on experimental osteoporosis in beagles induced by ovariectomy and a low calcium diet was studied. Twelve female beagles, 15-18 months old, were divided equally into 3 groups. The first group of beagles were ovariectomized and then fed a low calcium diet, Ca: 0.08%, (ovariectomy plus low Ca diet group); the second group was subjected to the same procedure and diet plus daily injection of elcatonin, 1.0 u/kg, i.m., (elcatonin group); and the third group was fed a standard diet, Ca: 1.36%, (control group) for 6 months. The undecalcified bone sections from the iliac crest were analyzed using histomorphometric methods following in vivo double labeling with Calcein. In the ovariectomy plus low Ca diet group, there were a decrease in trabecular bone volume and an increase in both resorption and formation surface of the trabeculae compared with the control group. These changes of trabecular bone volume and resorption surface were significantly prevented by daily injection of elcatonin. The increase of formation surface of trabeculae and mineral appositional rate was noted in the elcatonin group in comparison with the ovariectomy plus low Ca diet group. These results suggested that elcatonin could prevent bone loss caused by deficiency of sex hormone and dietary calcium.

Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis.

A new 16-membered macrolide designated as rhizoxin was isolated as a toxin produced by Rhizopus chinensis, the causal agent of rice seedling blight . The skeletal structure was determined by detailed NMR spectroscopic investigation of this compound and of its derivatives. Rhizoxin induced at a concentration of 10 ng/ml abnormal swelling of rice seedling roots, which is one of the characteristic symptoms of this disease. This compound also exhibited potent antifungal activity but little effect against bacteria.