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Biomedical subjects

R Kodama

Publications and source records attributed to R Kodama.

At least 73 records · Page 4Linked to original sources
PubMed1993

Retinal differentiation from multipotential pineal cells of the embryonic quail.

Pineal cells of the embryonic quail are multipotent stem cells which are able to differentiate in vitro into pigmented epithelial cells, lens cells and skeletal muscle fibers. Neuronal expression was added in this study in the repertory of differentiating potency of pineal cells. We used immunohistochemical methods to characterize neuronal properties with antibodies against serotonin, GABA, tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the enzyme histochemistry for acetylcholinesterase activity. Cells in the culture were found to be positively stained with these methods, suggesting that embryonic pineal cells are neuropotent to differentiate various types of neuronal cells. We have studied the culture conditions which favor increment of neuronal cells with extension of neuritic processes, and we have found that neuronal cells are maintained for quite a long period under suppressive conditions of DNA synthesis and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA polymerase alpha, in the medium. Time lapse videograph revealed two different cell types participated in neurogenesis; a minor population of small round cells and a major one of flat epithelial cells. Since embryonic quail pineal cells have been shown to differentiate into two types of photoreceptors, the present results show wider retinal potency of cell differentiation by embryonic pineal cells. The cessation of DNA synthesis as well as growth factor(s) may be positively involved in the mechanisms of determination and differentiation of pineal neurons.

Animals↗
PubMed1993

Transdifferentiation.

Recent progress in studies of development and differentiation has greatly stimulated analysis of transdifferentiation, and more cell types capable of transdifferentiation have been documented. Growth factors must be essential, key factors in the regulation of the transdifferentiation process, in cooperation with components of the extracellular matrix, which helps to stabilize the differentiated state of tissues. Trials to induce transdifferentiation artificially by transfection of genes have also begun.

Animals↗
PubMed1993

[Experimental study in Japanese monkeys with Helicobacter pylori infection].

Japanese monkeys were studied for one month from 6 months (short-term) after inoculation of Helicobacter pylori, and two years (long-term). In the short-term study, macroscopic and histological gastritis were observed for 5 infected monkeys. The gastritis score, the ammonia concentration in the gastric secretion and the level of serum antibody (IgG) were higher for the infected group than for the control. In the long term study, H. pylori was always recovered for 2 years in the infected group, and the gastritis score was higher than the control. The intracellular periodic acid-Schiff (PAS) positive substances in the infected group decreased than that of the control. The tall of pyloric gland in the infected group was significantly decreased on 6 months from 1.5 years. These results suggest that the Japanese monkey can be used as experimental model of H. pylori infection and that H. pylori can induce chronic active gastritis similar to human.

Animals↗
PubMed1993

[Eradication therapy of Helicobacter pylori in gastroduodenal ulcer and its long-term course].

We investigated the efficacy of antimicrobial drugs, amoxicillin and clarithromycin that have the in vitro activity against H. pylori, and observed a long term course of ulcer after eradication. The eradication rate of combination therapy with PPI and amoxicillin showed best result (13/18: 72%). In eradicated cases, index of PAS positive substance and gastritis score in antral mucosa that is histological examination was improved, and ammonia concentration in gastric secretions decreased. The recurrent rate of ulcer in long term course after eradication was investigated, the recurrent rate of ulcer was significantly lower in H pylori eradicated cases than in H. pylori continuously positive cases. Results suggest that eradication of H. pylori may be controlled recurrence of H. pylori positive peptic ulcer.

Amoxicillin↗
PubMed1993

Basic fibroblast growth factor as one of the essential factors regulating lens transdifferentiation of pigmented epithelial cells.

In vitro transdifferentiation of retinal pigmented epithelial cells of the chick embryo into lens cells can be markedly enhanced by culture in the presence of testicular hyaluronidase and phenylthiourea. Since the commercial preparations of hyaluronidase that had previously been used were very crude, a search for the actual effective molecule(s) enhancing lens transdifferentiation was conducted. First, we purified the enzyme and tested the effect of the purified hyaluronidase. Highly purified hyaluronidase itself did not enhance lens transdifferentiation. The crude hyaluronidase was then separated according to affinity with heparin, considering the possibility that the fibroblast growth factor (FGF) is contained in the crude hyaluronidase. Transdifferentiation-enhancing activity was detected in the fraction which was bound to heparin and eluted with 2 M NaCl, where no hyaluronate-degrading activity existed. Analysis of the fraction by SDS-PAGE revealed the existence of an 18 kDa protein whose NH2-terminal sequence was identical to that of basic FGF. The basic FGF derived from bovine brain also enhanced lens transdifferentiation of pigmented epithelial cells. These findings suggest that basic FGF must play a major role in enhancing transdifferentiation of pigmented epithelial cells to lens cells.

Amino Acid Sequence↗
PubMed1992

[Reproductive and developmental toxicity studies of FUT-187. (I)--Fertility study in rats with oral administration of FUT-187].

FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development.

Administration, Oral↗
PubMed1991

Ultrastructural and immunocytochemical analysis of the circumferential microfilament bundle in avian retinal pigmented epithelial cells in vitro.

The dedifferentiated phenotype of pigmented epithelial cells in vitro is bipotential and is effected by environmental alterations mediated by the cell surface and associated cytoskeleton. We have begun an investigation into the role that contractile microfilaments play in maintaining cell contact and cell shape in retinal pigmented epithelial cells in vitro. In this paper, we report a structural analysis of the intersection of the circumferential microfilament bundle with the cell membrane of cultured pigmented epithelial cells from chick retina. Techniques of electron microscopy, including freeze-fracturing and deep-etching, reveal that microfilaments of this bundle associate with a junctional complex in the apical cell compartment and with membrane domains which are not components of the junction. Microfilaments link with the cell membrane either at their termini or along the membrane-apposed surface of the circumferential bundle. Furthermore, we report the immunocytochemical localization of filamin (a high molecular weight actin-binding protein, which forms fiber bundles and sheet-like structures when bound with F-actin in solution) in the circumferential/microfilament bundle.

Actin Cytoskeleton↗
PubMed1991

Ultrastructural observations of typical gap junctions in human foetal lens nucleus.

The ultrastructure of gap junctions throughout the human foetal lens was observed. By freeze-fracture analysis, we observed numerous gap junctions in both lens cortex and lens nucleus. Comparison between lens cortex and lens nucleus showed that the gap junctions of lens nucleus are characterized by extreme mosaics of closely apposed P- and E-faces in junctional areas, though no significant difference in the area of gap junctions was observed between lens cortex and lens nucleus. In addition, some morphological variations, such as the smooth domains without particles or pits in junctional areas and the reticulated figures of gap junctions, were observed only in the lens nucleus. We also observed by thin-section electron microscopy that cell membranes of human foetal lens nucleus, as observed in the lens cortex, are mainly composed of continuous lipid bilayer and junctional structures. We concluded that characteristic morphology of lens gap junctions, as observed in the cortex of human foetal lens, is mostly preserved in the human foetal lens nucleus, although some depth-dependent alterations were also observed.

Fetus↗
PubMed1991

[Studies on distribution and excretion of squalane in dogs administered for 2 weeks].

In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19, 23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, the most important etiologic agent of Yusho, which was accumulated in the body of rat. We also reported that, in rats and dogs, squalane did not show any appreciable toxic signs during 3-month treatment, though a part of squalane was absorbed from gastrointestinal tract of dogs. In the present paper, we have investigated the elimination of absorbed squalane in beagle dogs. During the treatment with squalane orally at a dose of 1200 mg/kg/day for 14 days, the fecal excretion of squalane per day was 65-90% of the daily dose. After the treatment (on the day 14), squalane levels in blood and hair were about 30 ppm and 14640 ppm, respectively. On the day 56 after the first dosing, squalane was not detected in blood. On the day 70, squalane level in hair was reduced to about 1% of that on the day 14. Squalane levels in skin, liver, adipose tissue and small intestine on the day 70 were also reduced compared with that on the day 42. Moreover, small amount of squalane was still excreted into feces from the day 15 to the day 70. These results suggested that absorbed squalane was gradually excreted through feces and skin in dogs.

Administration, Oral↗
PubMed1990

Partial amino acid sequence of the major intrinsic protein (MIP) of the chicken lens deduced from the nucleotide sequence of a cDNA clone.

A cDNA clone of the major intrinsic protein (MIP) of the chicken lens was isolated. This clone covers the C-terminal half of the coding region and 3'-untranslated region including a polyadenylation signal. Comparison with the bovine MIP cDNA sequence revealed that: (1) the amphilphilic transmembrane helix in bovine MIP is highly hydrophobic in chicken MIP, and is thus unlikely to offer a hydrophilic lining of the transmembrane pore, and (2) the possible calmodulin binding site is conserved especially at amino acid residues which are postulated to be important in its binding with calmodulin. Northern blotting revealed the presence of transcripts of different lengths, two of which correspond closely to the transcripts of bovine MIP.

Amino Acid Sequence↗
PubMed1990

Acute toxicity tests of mofezolac (N-22) in mice and rats.

Mofezolac (N-22) is a newly developed analgesic and anti-inflammatory agent. The acute toxicities of N-22 were investigated in ICR mice and Wistar rats in oral (p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. LD50 values of N-22 in mice were 1528 mg/kg (p.o.), 275 mg/kg (i.p.) and 612 mg/kg (s.c.) for males, and 1740 mg/kg (p.o.), 321 mg/kg (i.p.) and 545 mg/kg (s.c.) for females. Those in rats were 920 mg/kg (p.o.), 378 mg/kg (i.p.) and 572 mg/kg (s.c.) for males, and 887 mg/kg (p.o.), 342 mg/kg (i.p.) and 510 mg/kg (s.c.) for females. The sex difference was not clearly observed in mice and rats, but the species difference was observed in p.o. routes. As an initial toxic sign, the hypoactivity was observed in mice and rats of all routes, subsequently, paleness of skin, anemic conjunctiva, emaciation, stupor and/or coma were observed in mice and rats of p.o. and i.p. routes. In rats of those routes, tonic and/or asphyxial convulsion and dyspnea were also observed. In pathological examination of mice and rats, gastrointestinal disorders were observed in p.o. and i.p. routes, and changes of subcutaneous tissue at the injection site were observed in s.c. route.

Administration, Oral↗
PubMed1990

[Fifty two-week chronic oral toxicity study of mofezolac (N-22) in beagle dogs].

The chronic toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in beagle dogs by oral administration of the test compound at dose levels of 1, 3, 6 and 12 mg/kg once daily for 52 weeks. The recovery study was also carried out by withdrawal for 5 weeks. 1. No death occurred during the administration and recovery periods in all groups, there were no abnormal findings due to N-22 administration on behavior and appearance, body weight and food consumption. 2. There were no abnormal findings due to N-22 administration on fecal test, urinalyses, hematological and biochemical examinations, hepatic and renal function tests, ophthalmological examination, electrocardiography, blood pressure and organ weight. 3. By histopathological examination, loss of villi in small intestine was found in one female of 6 mg/kg group, erosion in small intestine in one male of 12 mg/kg group, and shortening of villi and ulcer in small intestine in each one female of 12 mg/kg 4. Accordingly, the non-effective dose levels of N-22 were estimated to be 6 mg/kg for male and 3 mg/kg for female in this study.

Administration, Oral↗
PubMed1990

[Reproductive and developmental toxicity study of mofezolac (N-22) (3)--Teratogenicity study in rabbits by oral administration].

Mofezolac (N-22) is a new developed analgesic and anti-inflammatory agent. A teratogenicity study of N-22 was carried out in New Zealand White rabbits to examine the effect on the dams and the teratogenic potentiality. N-22 was administered orally at the dose levels of 12.5, 50 and 200 mg/kg during the organogenesis from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 28 of gestation and their fetuses were examined. There were no growth retardation and teratogenic effects on fetuses from the dams administered N-22, although the administration of 200 mg/kg produced a decrease in food consumption of the dams concomitant with the embryocidal effects as shown by an increase in the early resorption rate. Thus, non-toxic dose level of N-22 on the dams and fetuses was considered to be 50 mg/kg.

Abnormalities, Drug-Induced↗
PubMed1990

[Fifty two-week chronic oral toxicity study of mofezolac (N-22) in rats].

Fifty two-week oral toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in Wistar rats with dose levels of 5, 20, 60 and 120 mg/kg/day, and the 5-week withdrawal was followed for recovery study. Hematuria, blanching of the skin and suppression of body weight gain were observed in females given 120 mg/kg, and 9 of these prostrated and died from week 20 to week 52, or were euthanized when moribund. These symptoms were not seen in males at any dose levels. In 120 mg/kg group, increased positive cases of fecal occult blood were observed during the administration period, and the pathological examination revealed gastrointestinal lesions such as erosion, ulcer, hemorrhage and mucosal regeneration in the small intestine. Renal disorder was also involved mainly in females given 120 mg/kg, as shown by increase in urine volume with declined osmotic pressure and specific gravity, serum urea nitrogen, creatinine, inorganic phosphorus, and other related parameters. In addition to enlargement, rough surface and scar formation, dilated tubular lumen and papillary ducts of the kidney were observed as a main lesion. Incidental findings with those disorders, observed mainly in females given 120 mg/kg, included increase in leucocytes with high neutrophils ratio, and enlargement of the spleen, adrenals and mesenteric lymph node. There were some of the similar gastrointestinal and renal changes mainly in females given 60 mg/kg. Anemic findings were noted in both sexes of 120 mg/kg and in females of 60 mg/kg group, and mainly females given 120 mg/kg showed increase in platelets, reticulocytes and fibrinogen, shortening of blood coagulation time, as well as extramedullary or accented hematopoiesis of the liver, spleen and bone marrow. Other serum biochemical changes observed mainly in females given 120 mg/kg were decrease or decreasing trend in total protein, A/G ratio, and transaminase activity. Fine structure of the liver from females given 20 mg/kg or more revealed cisternal dilatation of smooth-surfaced endoplasmic reticulum of hepatocytes, and the increased liver weight was observed in females given 120 mg/kg. Accordingly, non-effective dose level of N-22 in 52-week chronic toxicity study was estimated to be 20 mg/kg for males and 5 mg/kg for females.

Administration, Oral↗
PubMed1989

Ontogenesis of alpha 2-adrenoceptor coupling with GTP-binding proteins in the rat telencephalon.

The ontogenesis of alpha 2-adrenoceptors and GTP-binding proteins and their coupling activity were investigated in telencephalon membranes of developing rats. The manganese-induced elevation of [3H]clonidine binding was increased in an age-dependent manner but the guanosine 5'-O-(3-thio)triphosphate-induced decrease in binding did not change. The extent of the binding of [3H]clonidine at 15 nM (saturable concentration) increased in an age-dependent manner and reached the adult level at 4 days after birth. Cholera toxin and pertussis toxin catalyzed ADP-ribosylation of proteins of 46 and 41/39 kilodaltons (kDa) in solubilized cholate extracts of the membranes. The 41/39-kDa proteins ADP-ribosylated by pertussis toxin (Gi alpha + Go alpha) were increased with age and reached the adult level at day 12, whereas the 46-kDa protein (Gs alpha) reached its peak on day 12 and then decreased to the fetal level at the adult stage. The immunoblot experiments of the homogenates with antiserum (specific antibody against alpha- and beta-subunit of GTP-binding proteins) demonstrated that the 39-kDa alpha-subunit of (Go alpha) and the 36-kDa beta-subunit of GTP-binding protein (beta 36) increased with postnatal age. In contrast, 35-kDa beta-subunit (beta 35) did not change. From these results, it is suggested that the coupling activity of alpha 2-adrenoceptor with GTP-binding protein gradually develops in a manner parallel with the increase of alpha 2-adrenoceptor and pertussis toxin sensitive GTP-binding proteins, Gi, and that alpha 39 beta 36 gamma may be related to the differentiation and/or growth of nerve cells in rat telencephalon.

Adenosine Diphosphate Ribose↗
PubMed1989

[Gene expression during lens transdifferentiation from pigmented epithelial cells].

Pigmented epithelial cells of chicken and human dedifferentiate in the medium containing phenylthiourea and testicular hyaluronidase, and then trans-differentiate into lens cells in vitro. To understand the molecular mechanisms of transdifferentiation, gene expression during lens transdifferentiation was analyzed. As the first step, pigment cell and lens specific genes were isolated and expression of these gene was analyzed by Northern blotting . These results clearly shown that lens transdifferentiation proceeds via neutral cell state in which both pigment and lens specific genes are repressed. Oncogene expression was also analyzed. An elevated expression of the c-myc gene was observed during dedifferentiation process. It is expected that elevated expression of c-myc gene might prevent the cells from entering the G0 phase and thus lead to dedifferentiated state.

Animals↗