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Biomedical subjects

N Chida

Publications and source records attributed to N Chida.

At least 37 records · Page 2Linked to original sources
PubMed1996

Differentiation-dependent enhanced expression of protein phosphatase 2Cbeta in germ cells of mouse seminiferous tubules.

The presence of five distinct isoforms of protein phosphatase 2Cbeta (PP2Cbeta-1 approximately -5) is known. In this study, we demonstrate that the mRNA levels of PP2Cbeta-3, -4 and -5 and PP2Cbeta protein level increased during the course of the first wave of spermatogenesis in neonatal mouse testis. Northern blot and in situ hybridization analyses revealed that PP2Cbeta-3, -4 and -5 were expressed predominantly in pachytene spermatocytes and in more highly differentiated germ cells. The substrate specificity of PP2Cbeta-4 determined with artificial substrates differed from those of PP2Cbeta-3 and -5, suggesting that the difference in the structure of PP2Cbeta-3, -4 and -5 reflect their unique physiological functions in testicular germ cells.

Animals↗
PubMed1996

Enhanced UV sensitivity of yeast cells induced by overexpression of Mg(2+)-dependent protein phosphatase alpha (type 2C alpha).

The UV sensitivity of wild-type Saccharomyces cerevisiae cells was increased 2-fold when rat Mg(2+)-dependent protein phosphatase alpha (protein phosphatase type 2C alpha) was overexpressed in the cells. The overexpression of this enzyme rendered the rad 18 mutant (defective in postreplication repair) more UV-sensitive than was observed in the wild-type cells. However, this increase in UV sensitivity disappeared when the host cells had a rad 1 mutation (defective in excision repair). These results suggest that the Mg(2+)-dependent protein phosphatase overexpressed in the yeast cells inhibited their excision repair system.

Animals↗
PubMed1996

[Renal function in children with reflux nephropathy followed up more than 10 years after disappearance of vesicoureteral reflux: usefulness of alpha 1-microglobulin as a marker to predict the prognosis of these children].

BACKGROUND: Although reflux nephropathy (RN) is one of the most important causes of renal failure in adolescence and young adulthood, we have no appropriate markers to know the future course of children with RN. In order to find out useful marker to predict the prognosis of these children, we analyzed the result of over ten years follow-up of children with RN. METHODS: We evaluated renal function in 25 patients (aged between 11 years and 23 years, 14 males and 11 females) with RN using urinary alpha 1-microglobulin (alpha 1 m), urinary albumin and 99mTc-dimercaptosuccinic acid (DMSA) renal scan. All patients were followed up more than 10 years after disappearance of vesicoureteral reflux. RESULTS: Of 25 patients, 13 showed high levels of urinary alpha 1 m (> 4.4 mg/gCr = upper normal limit) during follow-up period. Among them, renal dysfunction developed in 9 on DMSA renal scan and/or serum creatinin (Cr) level. Before puberty, all patients, even children with renal dysfunction (serum Cr > 1.0 mg/dl), remained in normal or slight high urinary albumin levels. Five cases, showed high levels of urinary alpha 1 m before puberty, demonstrated a remarkable increase of urinary albumin levels after puberty. CONCLUSION: From these results, it was suggested that urinary levels of alpha 1 m could be utilized as a marker to predict the prognosis of children with RN.

Alpha-Globulins↗
PubMed1995

FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (1) In vitro effects on human and animal prostatic enzymes.

Steroid 5 alpha-reductase is an enzyme which converts testosterone into 5 alpha-dihydrotestosterone (DHT) and is implicated in the pathogenesis of benign prostatic hyperplasia (BPH) in men. We studied in vitro effects of FK143, a nonsteroidal new compound, on 5 alpha-reductase in human and animal prostates. Prostates were obtained from Wistar rats, Beagle dogs, and Cynomolgus monkeys as well as prostatic tissue from BPH patients obtained by the prostatectomy. Nuclear membrane fraction of prostates showed pH dependent 5 alpha-reductase activities, and inhibitory effects of drugs were assayed at pH 6.5. FK143 inhibited human prostatic 5 alpha-reductase in a dose-dependent manner with an IC50 of 1.9 nM and also inhibited animal 5 alpha-reductases with similar IC50 values. FK143 inhibited human and rat 5 alpha-reductases in a noncompetitive fashion while finasteride, a steroidal 5 alpha-reductase inhibitor, showed competitive inhibition. The affinities of FK143 for the human 5 alpha-reductase is constant at pH 5 and 6.5. No inhibitory effects were shown to other oxidoreductases. These results indicate that FK143 is a new type of potent and selective 5 alpha-reductase inhibitor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (2) In vivo effects on rat and dog prostates.

FK143 is a nonsteroidal new inhibitor of steroid 5 alpha-reductase, an enzyme which converts testosterone into 5 alpha-dihydrotestosterone (DHT). We studied in vivo effects of FK143 on rat and dog prostates. FK143 was orally administered to mature male rats for 14 days. At doses above 1 mg/kg, FK143 significantly reduced the wet weights of the ventral prostate and seminal vesicle, but showed no effects on those of the epididymis, testis, and adrenal. Growth of ventral prostate and seminal vesicle was induced by the subcutaneous injection of testosterone propionate (TP) in the castrated young rats and was reduced by FK143 administration at doses above 3.2 mg/kg, while growth induced by 5 alpha-dihydrotestosterone propionate (DHTP) was not affected. FK143 had no binding affinity for the rat androgen receptor. FK143 showed neither estrogenic and antiestrogenic effects on the rat uterus nor androgenic effect on the rat prostate. Concentration of testosterone and DHT in the rat and dog prostates were measured by GC-MS, and administration of 10 mg/kg of FK143 significantly reduced the intraprostatic concentration of DHT. These results indicate that FK143 reduced the prostate growth by inhibiting 5 alpha-reductase activities in the prostates.

5-alpha Reductase Inhibitors↗
PubMed1995

Injection of ethanolamine oleate into a segmental portal branch for pharmacologic hepatic segmentectomy in dogs.

RATIONALE AND OBJECTIVES: Currently available treatments for hepatocellular carcinoma are not satisfactory in terms of recurrence rates. In this study, we injected ethanolamine oleate (EO) into a portal branch in an attempt to cause necrosis of a liver segment in which hepatocellular carcinoma might be located. METHODS: Nine dogs received EO injections via a balloon catheter into a segmental portal branch of the liver. RESULTS: Immediately after injection, 80-100% of the liver cells in the EO-injected segment underwent coagulative necrosis. After 1 week, the EO-injected segment had become completely necrotic in two dogs. Only a few viable hepatocytes were still observed around the arteries and beneath the liver capsule in another dog. No pathologic changes were observed in the lungs, kidneys, or heart of any dog. There was a correlation between the EO dosages and the volume of the EO-injected liver tissue. CONCLUSION: EO injection into a portal branch results in the pharmacologic destruction of the corresponding liver segment. This procedure may be beneficial in the treatment of hepatic malignancies.

Animals↗
PubMed1995

Crossed ureteral ectopia with an ectopic blind-ending ureter.

A rare case of multiple urological anomalies is presented. The chief complaint of the patient, a 12-year-old girl, was urinary incontinence. Radiologic and endoscopic examinations revealed that the patient had a normal left kidney and ureter, a left ectopic blind-ending ureter that opened near the neck of the bladder, and right complete double ureters with an ectopic orifice that opened on the left of the external urethral meatus. This orifice was responsible for her urinary incontinence. Right ureteroneocystostomy was performed and the incontinence was cured. An attempt was made to explain the embryological origin of the anomalies observed in this case. We postulated that during development, on the left, there were three ureteral buds on the mesonephric duct. The first bud was at the normal position and drained the left kidney in a normal manner. The second bud was cranial from the normal position on the mesonephric duct and was associated with growth in an abnormal direction. This bud made contact with the upper portion of the right metanephric mass. The last bud grew between the two aforementioned buds. This bud was not draped by the metanephric mass and became the blind-ending ureter. On the right, one ureteral bud was located on the mesonephric duct and it made contact with a metanephric mass that became the right kidney. The upper part of the right kidney was drained by the ureter that had originally been located on the left mesonephric duct. This condition should be termed crossed ureteral ectopia rather than crossed renal ectopia, since the ureter was the structure that crossed.

Child↗
PubMed1995

Novel steroid 5 alpha-reductase inhibitor FK143: its dual inhibition against the two isozymes and its effect on transcription of the isozyme genes.

Recent cloning of the cDNAs for the two isozymes of steroid 5 alpha-reductase (EC 1.3.99.5) allowed individual expression of the isozymes and permitted us to investigate the action of steroid 5 alpha-reductase inhibitors against the individual isozymes without any ambiguity that may be caused by coexistence of the isozymes in tissue preparations. We examined the kinetic characteristics of FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1- yl]butyric acid), a novel nonsteroidal steroid 5 alpha-reductase inhibitor against cloned human and rat steroid 5 alpha-reductase isozymes. FK143 was shown to inhibit both isozymes equally. The mode of the inhibition of FK143 against both isozymes was noncompetitive. The inhibition constants Kie and Kies of FK143 for human types 1 and 2 were 27.0 and 19.6 nM and 19.9 and 14.5 nM, respectively. Species selectivity between human and rat of the inhibitory activity of FK143 against both isozymes was not found. We also examined the effect of FK143 on the in vivo expression of the genes encoding for the rat steroid 5 alpha-reductase isozymes. FK143 reduced the testosterone-induced increase in the amount of the type 1 mRNA in castrated rat, whereas it did not substantially affect the amount of the type 2 mRNA.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Spermine promotes the survival of primary cultured brain neurons.

The effects of polyamines on the survival of hippocampal and cerebellar neurons in primary culture were investigated. Putrescine and spermidine showed no effects on the neuronal survival, while spermine increased significantly the number of surviving neurons in both hippocampal and cerebellar cultures. The concentration-effect curve for spermine was bell-shaped with the maximum effect at a concentration of 10(-8) M. The survival-promoting effect of spermine was blocked by ifenprodil, an antagonist at the polyamine site of the NMDA receptor channel complex. These results suggest that spermine exerts trophic effects on brain neurons through an ifenprodil-sensitive mechanism.

Animals↗
PubMed1993

Emetic responses of Sorex unguiculatus.

We have shown previously that Suncus murinus, a species of the insectivore, can vomit in response to various emetogenic stimuli. In the present study we investigated whether or not Sorex unguiculatus, which belongs to different subfamily (Soricinae) of insectivore, vomits in response to emetogenic drugs. Subcutaneous injection of veratrine and oral administration of copper sulfate caused emesis in the animal. Histological study showed that bilateral structure of the area postrema was not important for the emetic reflex. Therefore, the capability of emesis may be common to the family of soricidae of the insectivore, and the Sorex unguiculatus is the smallest known mammal which can vomit.

Animals↗
PubMed1992

Synthesis of (+)- and (-)-nojirimycin and their 1-deoxy derivatives from myo-inositol.

The conversion of the naturally abundant cyclitol, myo-inositol (4), into (+)-nojirimycin (1a), its enantiomer (1b), and their 1-deoxy analogues (2a and 2b) is described. Biological assay of 2a, 2b, and the bisulfite adducts of 1a and 1b (3a and 3b) showed that the compounds having the unnatural L-gluco configuration (2b and 3b) possess moderate-to-high inhibitory activity against almond beta-D-glucosidase and bovine liver beta-D-galactosidase.

1-Deoxynojirimycin↗
PubMed1992

Spermine facilitates the generation of long-term potentiation of evoked potential in the dentate gyrus of anesthetized rats.

The effects of the polyamines, spermine, spermidine and putrescine, on long-term potentiation (LTP) of evoked potential were investigated in the dentate gyrus of anesthetized rats. Injection of 5 nmol spermine into the lateral ventricle did not influence the basal amplitude of the population spike, but significantly enhanced the potentiation induced by subthreshold tetanic stimulation (20 pulses at 60 Hz). The effect of spermine resulted in facilitation of LTP generation. Injection of the same dose of spermidine or putrescine affected neither the basal response nor the potentiation induced by subthreshold tetanus at all, indicating that the LTP-facilitating effect is specific to spermine. Furthermore, the LTP-facilitating effect of spermine was dose-dependent in the range of 0.5-50 nmol. When 5 nmol ifenprodil, an antagonist at the polyamine site of the NMDA receptor channel complex, was concomitantly injected, spermine could not facilitate the generation of LTP. Since injection of ifenprodil alone did not influence the generation of LTP, it is probable that ifenprodil specifically blocks the effect of spermine. These results suggest that spermine facilitates the generation of hippocampal LTP, probably through an ifenprodil-sensitive polyamine site associated with the NMDA receptor.

Adrenergic alpha-Antagonists↗
PubMed1992

Prenatal diagnosis in high risk pregnancies for Zellweger syndrome.

Zellweger syndrome is a lethal disorder. At present, no effective therapies are known for the patients of Zellweger syndrome. Recently a typical case of Zellweger syndrome in Japan was observed. In spite of intensive care, the patient died at the age of 3 months. Following this, the parents requested prenatal diagnosis for their following two pregnancies. We investigated levels of very long chain fatty acids (VLCFA), levels of bile acids in amniotic fluid and immunoblotting of peroxisomal beta-oxidation enzymes in cultured amniocytes. We report that immunoblotting using cultured amniocytes is an effective method for prenatal diagnosis of Zellweger syndrome. Furthermore, if we use immunoblotting for prenatal diagnosis, we can discriminate pseudoZellweger syndrome from pseudoneonatal adrenoleucodystrophy. Following prenatal diagnosis, two healthy babies were delivered. After birth, no abnormal levels of VLCFA in either serum or red blood cell membranes were confirmed. In this paper, we report that we can diagnose a healthy fetus in a high risk pregnancy for Zellweger syndrome.

Amniocentesis↗