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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 433 records · Page 24Linked to original sources
PubMed1991

Effects of vitamin E administration on platelet function and serum lipid peroxides in DOCA-salt hypertensive rats.

Effects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum lipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.

Animals↗
PubMed1991

H-ras expression, genetic instability, and acquisition of metastatic ability by rat prostatic cancer cells following v-H-ras oncogene transfection.

To study the relationship between metastatic ability, mutated H-ras expression, and genetic instability, a cloned, nonmetastatic rat prostatic cancer cell line (AT2.1) was transfected with the v-H-ras oncogene. The parental AT2.1 clone, 4 control transfectants (Neo/Only), and 9 v-H-ras transfectants (Neo/Ras) were characterized with regard to their H-ras content by using Southern, Northern, and Western blot analysis and their biological behavior in vivo. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors. All 4 (Neo/Only) transfectants like the parental untransfected cell were non-metastatic. Six of 9 Neo/Ras transfectants were metastatic to the lungs and lymph nodes, while the other 3 Neo/Ras transfectants were not metastatic. There was no simple dose-response relationship between the level of v-H-ras integration, mRNA or p21 protein expression, and the development of metastatic ability by the Neo/Ras transfectants. Cytogenetic analysis demonstrated that the frequency of additional structural and/or additional numerical chromosomal changes among the Neo/Ras transfectants was significantly higher than that in the Neo/Only transfectants (P less than 0.05). Loss of chromosome 10 was observed in all of the Neo/Ras transfectants, whereas that was observed in only one of the 4 Neo/Only transfectants (P less than 0.05). There were no specific chromosomal changes, however, which were statistically correlated with the development of metastases in the Neo/Ras transfectants. These results demonstrate that development of the metastatic ability in AT2.1 cells is not a single-step reaction regulated by the level of H-ras expression alone, but rather a complex process requiring additional events. One of the additional events appears to be an increase in genetic instability and cytogenetic changes following v-H-ras transfection.

Animals↗
PubMed1991

Localization of hydroxyindole O-methyltransferase-synthesizing cells in bovine epithalamus: immunocytochemistry and in-situ hybridization.

Hydroxyindole O-methyltransferase (HIOMT)-immunoreactive cells and melatonin synthesis were demonstrated in bovine epithalamus (including the pineal gland) with monoclonal antibodies and cRNA probes to HIOMT. The HIOMT-immunoreactive product was present in the cytoplasm of pinealocytes. All identifiable pinealocytes were clearly labeled in the pineal gland. The expression of the HIOMT gene was first identified in pinealocyte cytoplasm by in-situ hybridization (ISH). The distribution of the hybridization-positive cells in the pineal gland was compatible with that revealed by immunocytochemistry using the monoclonal antibody to HIOMT. In addition, HIOMT transcripts were found in the medial habenular nucleus, and the habenular and posterior commissure; they may correspond to S-antigen-immunoreactive cells demonstrated in the same regions of the hamster and the mouse. In these regions, the hybridization-positive cells did not exhibit HIOMT-immunoreactivity; thus, cells devoid of immunoreactivity may synthesize but rapidly transport the newly synthesized proteins. These results indicate (1) that the conversion of N-acetylserotonin into melatonin takes place in the cytoplasm of pinealocytes, (2) that some epithalamic cells in the habenular area may synthesize melatonin, and (3) that melatonin may act as a chemical messenger in centrally directed processes, as shown by using S-antigen immunocytochemistry.

Acetylserotonin O-Methyltransferase↗
PubMed1991

In situ hybridization histochemistry of Spot 35 protein, a calcium-binding protein, in the rat brain.

Using in situ hybridization, we analyzed the localization of mRNA for Spot 35 protein (Spot 35), a calcium-binding protein of the EF-hand type, in the rat cerebellum at various developmental stages. A cDNA fragment corresponding to part of the 3'-noncoding region was 35S-labeled and used as a hybridization probe. Autoradiographic signals for Spot 35 mRNA were detected in all the Purkinje cells, but not in any other neurons or glial cells in the adult rat cerebellum. There was no significant difference in signal intensity among individual cells. The signals were observed exclusively in Purkinje cell bodies, but not in their processes, in striking contrast to previous immunohistochemical studies in which Spot 35 protein was demonstrated in both cell bodies and processes. In the time-course study, signals for Spot 35 mRNA were detected in Purkinje cell bodies weakly at embryonic day 19, thereafter more intensely at more developed stages and most intensely at postnatal days 30 and 60 (adulthood). The signal intensities of individual cells were similar at each of these developmental stages except for the very early stages at which signals were weak and slightly variable among cells. These findings, especially that of the characteristic coordinated expression of Spot 35 mRNA at given stages, should prove useful in studies of degenerative diseases in the cerebellum in experimental animals and man. A weak expression of Spot 35 mRNA in some of non-Purkinje cells was also noted.

Animals↗
PubMed1991

Structure of the adduct of 16 alpha-hydroxyestrone with a primary amine: evidence for the Heyns rearrangement of steroidal D-ring alpha-hydroxyimines.

16 alpha-Hydroxyestrone, a product of estrogen 16 alpha-hydroxylation in humans that is suspected to be implicated in cell transformation, has been found to form stable adducts with nuclear components. The stable covalent adduct formed from 16 alpha-hydroxyestrone with 2-methoxyethylamine via the Heyns rearrangement of the alpha-hydroxyimine was identified as 3-hydroxy-17 beta-(2-methoxyethylamino)estra-1,3,5(10)-trien-16-one. Since the same product was obtained from 16 beta-hydroxyestrone with the amine, the alpha-hydroxyenamine is the most likely intermediate of the Heyns rearrangement. The adduct was fairly stable at 37 C in phosphate buffer (pH 7.4)/methanol (1:1 v/v), while the adduct formed from 16-oxoestradiol was disrupted reversely and completely within 6 hours. The evidence suggests that N-(3-hydroxy-16-oxoestra-1,3,5(10-trien-17 beta-yl)amine is the partial structure of the stable adducts formed from D-ring alpha-ketol estrogens with proteins.

Amines↗
PubMed1991

Glycemic response and fiber content of some foods.

The proposed mechanisms for the action of dietary fiber (DF) on the glycemic response suggest a nonlinear relationship between glycemic index (GI) and DF content. This relationship was analyzed by using the newly reported total DF (TDF) values, assuming a nonlinear regression curve. The empirical equation obtained was Y = 19.9X-0.322. Similar regression curves were also obtained for soluble DF (SDF) and insoluble DF (IDF). The two regression curves indicated that the correlation coefficient between observed GI and GI calculated from the IDF regression curve (-0.781) was virtually identical to that for SDF (-0.780), but a given content (eg, 5% vs available carbohydrate) of SDF gave a lower GI (39) than did IDF (48). This stronger dependency of GI on SDF suggests a major function of SDF in the TDF hypoglycemic effect. From the regression curve of GI vs TDF, we propose a supplemental GI to predict the glycemic response to foods with no published GI.

Blood Glucose↗
PubMed1991

Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus.

This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus. The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9% and 71.4% of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4+ T cells from diseased animals. This is the first experimental model of a (T cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.

Animals↗
PubMed1991

Utilization and metabolism of [U-14C]4' galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rats.

O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl- (1----4)-D-glucopyranose (designated as 4'GL) are produced from lactose with Cryptococcus laurentii OKN-4. Excretion and metabolism of 4'GL in rats were examined using a radioisotope technique. [U-14c]4'GL was synthesized from [U-14C]lactose by Cryptococcus laurentii OKN-4. The 14CO2 in expired air was counted after oral administration of [U-14C]4'GL or [U-14C]lactose in conventional rats, rats treated with antibiotics and germ-free rats. The rate of 14CO2 excretion from conventional rats given [U-14C]4'GL was slower than that from those administered [U-14C]lactose. When [U-14C]4'GL was orally administered to rats given antibiotics, there was a 2-h delay in 14CO2 excretion, as compared to conventional rats. In germ-free rats, total excretion of 14CO2 from [U-14C]-4'GL decreased to about one-third of that of conventional rats during a 24-h period. Radioactivities in the serum, liver, and carcass of the [U-14C]4'GL oral administration group were lower than those of the [U-14C]lactose oral administration group. Radioactivities in the feces and urine however, were higher in [U-14C]4'GL group than in [U-14C]lactose group.

Animals↗
PubMed1991

Kidney injury induced by lipid peroxide produced by vitamin E deficiency and GSH depletion in rats.

Four-week-old Wistar male rats were fed a vitamin E (VE)-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then intraperitoneally treated with buthionine sulfoximine (BSO) at 1 mmol/kg body weight once a day for 3 days. Glutathione (GSH) depletion by BSO treatment caused injuries especially in the kidneys of VE-deficient rats. The kidney weight increased in the VE-deficient rats after BSO treatment (0E-BSO). It was observed that the epithelial cells of the renal tubules in this group were strongly impaired and the injuries were necrosis and desquamation. No injury was observed in the kidneys of the BSO-untreated 0E group and the 10E groups. The TBA value of the kidney of 0E-BSO group was lower than that of the BSO-untreated 0E group, but the lipofuscin content of the kidney of the 0E-BSO group was 10 times higher than that of the BSO-untreated 0E group. These results suggest that the kidney injuries in rats may be caused by lipid peroxidation induced by vitamin E deficiency and glutathione depletion.

Animals↗
PubMed1991

Genetic factors and metastatic potential of prostatic cancer.

When a non-metastatic subline from the Dunning rat prostatic cancer was transfected with the v-Ha-ras oncogene, some transfectants acquired metastatic potential. Molecular analysis demonstrated that there was no simple dose-response relationship between v-Ha-ras expression and metastatic potential in this prostatic cancer system. Cytogenetic analysis on the same system demonstrated increased genetic instability following v-Ha-ras transfection. Progression of prostatic cancer from no metastatic to high metastatic potential may involve the loss of a metastasis suppressor gene. To test this possibility, non-metastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When the non-metastatic primary tumours were passaged in vivo, distant metastases developed in occasional animals. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of normal chromosome 2. These studies show that metastasis is associated with the loss of a specific chromosome. These studies also suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2. A more direct approach to identify a chromosome(s) carrying metastasis suppressor gene(s) by using microcell mediated chromosome transfer is currently progressing.

Adenocarcinoma↗
PubMed1990

Localization and synaptic effects of inhibitory vestibulocollic neurons activated by the posterior semicircular canal nerve in the cat.

Cellular locations, axonal projections, and synaptic effects of inhibitory vestibulocollic (VC) neurons activated by the ampullary nerve of the posterior semicircular canal (PCN) were studied in anesthetized cats. The inhibitory VC neurons were identified by their monosynaptic responses to PCN stimulation and by their antidromic responses to stimulation of the ipsilateral (i-) and contralateral (c-) neck extensor motoneuron pools, which are inhibitory targets of the PCN. They were classified as VCi (vestibulocollic neuron sending an axon to the i-neck extensor motoneuron pool) and VCc (vestibulocollic neuron sending an axon to the c-neck extensor motoneuron pool) neurons. Neither VCi nor VCc neurons were activated antidromically by localized stimulation of the ascending medial longitudinal fasciculus (asc. MLF) or the 3rd nuclei. Their cell somata were localized in the rostral part of the descending vestibular nucleus and the ventral part of the lateral vestibular nucleus. VCi and VCc neurons produced unitary IPSPs in neck extensor motoneurons in the C1 segment.

Action Potentials↗
PubMed1990

Characterization of an N-methyl-N-nitrosourea-induced autochthonous rat bladder cancer model.

Cohorts of 4- to 5-wk-old female Fischer 344 rats received four biweekly 1.5-mg doses of N-methyl-N-nitrosourea (MNU) intravesically and were sacrificed at various intervals. By 13 wk after initiation of the carcinogen, all animals have flat epithelial atypia and/or papillary transitional cell bladder carcinomas, and 67% of the lesions are histological Grade II or III. By 20 wk, 83% have gross bladder wall muscle-invasive tumors that eventually kill the host. There was no gross evidence of visceral metastases in any animal. This rat model of transitional cell carcinoma of the bladder is useful because: (a) all animals develop progressive neoplastic changes in situ within 4 mo after initiation of MNU treatment; (b) these lesions progress to grossly detectable bladder tumors which invade the bladder wall and kill the host; (c) this full progression of bladder epithelial cells from atypical hyperplasia through flat carcinoma in situ to transitional cell carcinoma occurs at discrete time points; (d) the histology of the grossly detectable tumors is that of invasive transitional cell carcinomas; and (e) no leukemias, breast cancers, lymphomas, or other non-bladder tumors are induced. Six MNU-induced bladder wall-invasive tumors were karyotyped, and all tumors were diploid with 42 chromosomes. Three of the tumors had apparently normal karyotypes, while three tumors had karyotypes containing one or more cytogenetic structural markers. One of these markers (i.e., 8p+) was observed in two of the three tumors. The level of expression of total ras p21 (N-, Ki-, and Ha-ras p21) and codon 12-mutated c-Ha-ras p21 (i.e., glycine to glutamic acid mutation in codon 12) in a series of these MNU-induced bladder tumors was determined by Western blot analysis. No increase in the total ras p21 nor any expression of codon 12-mutated c-Ha-ras p21 was detected in any of these tumors.

Animals↗
PubMed1990

Genetic instability and the acquisition of metastatic ability by rat mammary cancer cells following v-H-ras oncogene transfection.

When nonmetastatic dimethylbenzanthracene-induced rat mammary cancer cells (RMC1) were transfected with a control plasmid containing the neomycin resistance gene (i.e., Neo/Only), none of the five clonal Neo/Only transfectants isolated and characterized was metastatic, only one of five had a single structural chromosomal abnormality, and only one of five had a single numerical chromosomal change not present in the untransfected parental RMC1 cells. In contrast, when RMC1 cells were transfected with a plasmid containing both the neo resistance and mutated v-H-ras oncogene (i.e., Neo/Ras), four of nine clonal Neo/Ras transfectants isolated and characterized were highly metastatic, and all nine had multiple structural and/or additional numerical chromosomal abnormalities. The frequency of transfectants which had structural and/or additional numerical chromosomal changes in Neo/Ras transfectants was significantly higher than that in Neo/Only transfectants (P less than 0.05). In addition, seven of nine Neo/Ras transfectants had structural abnormalities in chromosome 1, whereas none of five Neo/Only transfectants had such abnormalities (P less than 0.05). All four Neo/Ras transfectants that were highly metastatic had structural aberrations involving a gain in chromosome 4. In contrast, none of the three Neo/Ras transfectants which were of low metastatic ability had a similar aberration involving chromosome 4. Correlation between a gain in chromosome 4 and a gain of high metastatic ability was significantly (P less than 0.05). These results demonstrate that, when RMC1 cells are transfected with v-H-ras, transfectants expressing the mutated v-H-ras p21 become genetically unstable and undergo chromosomal changes. These studies suggest that, if the appropriate chromosomal changes occur, these v-H-ras transfectants acquire high metastatic ability.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Paracrine growth stimulation of androgen-responsive Shionogi Carcinoma 115 by its autonomous subline (Chiba Subline 2).

Shionogi Carcinoma 115 cells (SC 115 cells) and Chiba Subline 2 cells (CS 2 cells) are clones of an androgen-responsive mouse tumor cell line and its autonomous subline, respectively. Since it was reported that the growth of cells from SC 115 was regulated by an androgen-induced fibroblast growth factor (FGF)-like peptide (1), the present study was aimed at examining whether a similar growth factor was secreted by CS 2 cells in the absence of testosterone. Although SC 115 cells did not grow in the serum-free medium without androgens, SC 115 cells could proliferate in mixed culture with CS 2 cells, suggesting stimulation of SC 115 cells by CS 2 cells. It was shown that CS 2 cells secreted a growth factor without the influence of testosterone, and this factor promoted the growth of SC 115 and CS 2 cells, as well as that of BALB/3T3 cells. The factor was partially purified from serum-free conditioned medium obtained from cultures of CS 2 cells. It showed an affinity for heparin, stability to heat and acid treatments, a decrease in activity when anti-basic FGF antibody was added to cultures, and an estimated molecular weight of approximately 50,000. Therefore, the factor seemed to have the nature of an FGF-like peptide. It was concluded that, in the absence of testosterone, CS 2 cells produced an FGF-like growth factor which controlled the growth of both CS 2 cells and parent SC 115 cells, in autocrine and paracrine manners, respectively.

Animals↗
PubMed1990

[A comparative study of histopathological findings of resectable pancreatic carcinoma (t1, t2 cases) with ERCP and CT images].

The diagnosis of pancreatic carcinoma at early stage has been considered very difficult. Histopathological findings of resectable pancreatic carcinoma less than 4 cm in size (t1, t2 cases) have been compared with endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) images for the purpose of improving the diagnosis of pancreatic carcinoma. Twenty-six patients with pancreatic carcinoma less than 4 cm in size, who underwent surgery at the National Cancer Center Hospital from January 1980 to December 1988, were analyzed. The mean age of these 26 cases was 64 years (range of 45 to 78 years), with 13 males and 13 females. Pancreatograms were classified into 4 groups such as stenosis, tapering, obstruction and others, and this classification was compared with histopathological findings. However, ERCP classification showed no correlation with histopathological findings. CT images of the margins, characteristics and density of the tumor were compared with histopathological findings. There existed a good correlation between CT images and histopathological findings such as histological differentiation, macroscopic type of cut surface and INF. For an accurate diagnosis of pancreatic carcinoma, it is important that localization of the tumor is diagnosed first by ERCP and the characteristics of the tumor should be recognized by CT images.

Adenocarcinoma↗