PubMed Health⌕ Search

Biomedical subjects

N Tokuda

Publications and source records attributed to N Tokuda.

At least 37 records · Page 2Linked to original sources
PubMed1997

Morphological and flow cytofluorometrical analyses of regenerated rat thymus after irradiation.

Reconstituted rat thymuses were studied by immunohistochemistry, transmission electron microscopy (TEM) and flow cytofluorometry on days 0, 1, 2, 3, 5, and 7 after whole-body sublethal irradiation (6 Gy). One day after irradiation, numerous apoptotic cells were seen in the cortical thymus; the percentage of the sub-G1 peak representing apoptotic cells was 8.9% in the DNA content histogram of cytofluorometry. On day 3, the thymic structure had been destroyed and no distinction was drawn between the cortex and medulla. In this stage, few thymocytes but many macrophages were present, and the percentage of the sub-G1 peak reached a peak at 13.0%. Bromodeoxyuridine (BrdU) incorporated cells gradually increased after irradiation, and immunohistochemically numerous apoptotic cells were found primarily in the cortex on day 7. These thymocytes showed some levels of electron density of the nucleus as revealed by TEM. The percentage of S phase cells did not change markedly (20-30%) based on one-color DNA content histograms, but the percentage of early S and S phase cells was extremely high on day 7 (70%). These data indicate that a part of DNA synthetic cells may result in apoptosis. The combination of immunohistochemistry, TEM and flow cytofluorometry to analyze DNA content and BrdU incorporation proved a useful tool for investigating the reconstituted thymus.

Animals↗
PubMed1997

Analysis of allogenic lymphocytes in rat thymus following sublethal irradiation.

The effects of allogeneic lymphocytes on the rat thymus following sublethal irradiation were investigated using immunofluorescence. The recovery of thymus weight following irradiation was delayed in rats 6 days after receiving lymphocytes compared to controls. Allogeneic cells forming colonies were detected by immunofluorescence in both the cortex and medulla of the host thymus, most frequently on day 15 when an appropriate number (3 x 10(6)) was injected. The allogeneic cells detected in the host thymus, presumably T lymphocytes, appeared to disturb thymic reconstitution following irradiation. However, double-immunofluorescence staining revealed that allogeneic cells did not affect the thymic stromal microenvironment. Allogeneic cells may have subsequently affected thymic tissue via cytokines. It is important to investigate not only the character of allogeneic cells in the host thymus but also the interactions of donor allogeneic cells, host immature lymphocytes and thymic epithelial cells because of the possibility that these allogeneic cells in the host thymus could prevent the rejection of allogeneic transplants.

Animals↗
PubMed1997

[A case of water intoxication presenting as urinary retention in a psychotic patient].

A 43-year-old man, who had been treated for chronic schizophrenia, was admitted to our hospital with the chief complaint of urinary retention. His serum levels of sodium and osmotic value were low and serum creatine phosphokinase (CPK) was elevated to 2,624 mg/dl. He had been consuming about 9 liters of water a day for ten years. A diagnosis of water intoxication was made and treated successfully with water restriction and drip infusion. To our knowledge, this is the 23rd case of water intoxication with serum creatine phosphokinase elevation reported in the Japanese literature and this is the first case with the chief complaint of urinary retention.

Adult↗
PubMed1996

Analysis of fetal rat liver using monoclonal antibodies.

BACKGROUND: In previous studies, we developed several monoclonal antibodies (mAbs) against fetal and adult rat liver to analyze the hemopoietic microenvironment of the fetal liver during the gestational period. In this study, we have developed two new mAbs against fetal rat liver cells and have examined the characteristics at various gestational ages of fetal liver and of adult liver. METHODS: The characteristics of these monoclonal antibodies were demonstrated by examining several tissues using immunohistochemical staining and flow cytofluorometry. RESULTS: Monoclonal antibodies HAM10 and HAM11 were developed against fetal rat liver cells. These reacted with the cytoplasm of fetal and adult hepatocytes. HAM10 antigen expression was strong at approximately day 18 of gestation in the active period of hemopoiesis in fetal rat liver but was much lower in adult liver. HAM10 antigen expression also increased in liver after partial hepatectomy and was reduced abruptly to a normal level thereafter. HAM11 antigen expression in fetal liver was weaker than that of HAM10 antigen expression. The degree of HAM11 antigen expression increased as gestation proceeded, reaching a maximum in adult liver. CONCLUSIONS: Both HAM10 and HAM11 antigens may play a role in the morphogenesis of hepatocytes and in the hemopoietic microenvironment for hemopoietic cells. Moreover, HAM10 antigen is may play a role in hepatocyte proliferation in the fetal liver, whereas HAM11 antigen may contribute to the maturation of fetal- to the adult-type hepatocytes.

Age Factors↗
PubMed1996

The effect of methylprednisolone on platinum kinetics and urinary enzyme excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro.

In order to evaluate the mechanism of the protective action of methylprednisolone against cisplatin-induced nephrotoxicity, platinum kinetics and urinary enzyme excretion following intravenous cisplatin, with or without methylprednisolone, were studied in vivo. The growth inhibition of LLC-PK1 cells by cisplatin in the presence or absence of methylprednisolone was studied in vitro. Rats intravenously injected with cisplatin combined with subcutaneous methylprednisolone 4 h prior to the cisplatin injection excreted more platinum in urine than rats treated with cisplatin alone. Both plasma and kidney platinum concentrations in rats injected with both cisplatin and methylprednisolone were significantly lower than those in rats given cisplatin alone at 4 h after cisplatin injection. However, there was no significant difference in urinary excretion of lactate dehydrogenase, gamma-glutamyl transpeptidase or N-acetyl-beta-D-glucosaminidase between methylprednisolone-treated rats and control rats. Methylprednisolone did not affect the inhibitory effects of cisplatin on the cell growth of LLC-PK1. These findings indicate that methylprednisolone-induced increase in urinary platinum excretion, accompanied by a decrease in plasma and kidney platinum concentrations following cisplatin injection in rats, may be one of the mechanisms responsible for the protective action of methylprednisolone.

Acetylglucosaminidase↗
PubMed1996

Influence of continuous interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats.

We have reported the efficacy of intraarterial-combined immunochemotherapy including interleukin-2 (IL-2) for unresectable hepatocellular carcinoma (HCC). To further test this therapy for prevention of intrahepatic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In addition, gap junction appearance, which may change during liver regeneration, was analyzed using a monoclonal antibody (HAM8). Serum albumin, alanine transaminase, and total bilirubin (TB) levels were also evaluated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. We also examined the influence of IL-2 on liver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, serum albumin, alanine transaminase, or TB was observed in any groups at 1, 2, or 4 days after hepatectomy. Neither IL-2 nor splenectomy influenced MI and BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline with or without splenectomy. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of IL-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. These results suggest that the liver regeneration after partial hepatectomy may be suppressed by the administration of IL-2, even though the suppression may not be harmful for overall recovery of the resected liver. However, it seems that hepatic IL-2 administration can be performed without serious complications after hepatectomy.

Alanine Transaminase↗
PubMed1996

The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors.

BACKGROUND: Many attempts have been made to reduce the nephrotoxicity of the anticancer agent cisplatin but the number of clinically useful modalities is very limited. Our previous experiments demonstrated that in rats methylprednisolone significantly reduces the nephrotoxicity caused by cisplatin. The present clinical study was conducted to confirm the protective effects of methylprednisolone against cisplatin nephrotoxicity. METHODS: Fourteen patients with urothelial tumors were injected with cisplatin according to the methotrexate, vinblastine, adriamycin, cisplatin (MVAC) therapy. Methylprednisolone was not administered during the first course of chemotherapy to provide a control, but was given in a dose of 2000 mg 2-3 hours before cisplatin during the second course of chemotherapy (treatment period) in each patient. Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase (GGTP), serum creatinine, and creatinine clearance (Ccr) were determined as indicators of the nephrotoxicity of cisplatin. Results were statistically analyzed by a paired t test to compare the nephrotoxic effects of cisplatin during the first course of chemotherapy (control period) with those during the second course of chemotherapy (treatment period). RESULTS: Methylprednisolone did not significantly inhibit the elevation in urinary enzyme excretion or serum creatinine levels following the cisplatin injection. However, the Ccr level after cisplatin infusion in the treatment period was significantly higher than that observed in the control period. CONCLUSION: The protective effects of methylprednisolone against cisplatin nephrotoxicity were indicated in this prospective clinical study.

Acetylglucosaminidase↗
PubMed1996

1,25-dihydroxyvitamin D3 stimulates phagocytosis but suppresses HLA-DR and CD13 antigen expression in human mononuclear phagocytes.

This study investigated the regulatory activity of 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) on phagocytic cells obtained from normal human peripheral blood. Flow cytometric analysis enabled identification of two discrete populations of cells, one predominantly monocytes ("monocyte" gate) and one containing primarily lymphoid and other cell types ("lymphoid" gate). The monocyte-associated antigens CD13 and CD33 were highly expressed by cells in this monocyte gate and used to monitor this population. Following 5 days of culture, cells in the monocyte gate manifested high phagocytic activity as determined by ingestion of fluorescent carboxylmicrospheres and exhibited high expression of class II HLA-DR products. 1,25-(OH)2D3 profoundly upregulated phagocytic activity while downregulating HLA-DR antigen expression on the cells in the monocyte gate. Moreover, 1,25-(OH)2D3 also reduced cell surface CD13 expression on the cells with low but not high phagocytic activity in this gate. Proportional activities by the 1,24-(OH)2D3 and 24,25-(OH)2D3 metabolites indicated the regulatory effects are likely mediated by the 1,25-(OH)2D3 receptor (VDR). Prostaglandin E2 (PGE2), a known modulator of monocyte/macrophage activity also markedly inhibited HLA-DR expression while enhancing the phagocytic activity of cells in the monocyte gate. In contrast to 1,25-(OH)2D3, PGE2 clearly upregulated CD13 expression in cells with high phagocyte activity. Since indomethacin, an inhibitor of PGE2 synthesis, failed to reverse the 1,25-(OH)2D3 induced inhibitory effect on HLA-DR expression, this effect is apparently not mediated through endogenous PGE2 synthesis. Based on these findings we speculate that 1,25-(OH)2D3 may be capable of acting as both an upregulating agent during natural immunity via the enhancement of phagocytosis by monocyte/macrophage populations and as a "downregulator" during acquired immune responses via an inhibitory effect on MHC class II antigen expression by professional antigen-presenting cells.

CD13 Antigens↗
PubMed1996

Major histocompatibility complex expression in muscle of rats with graft-versus-host disease.

Immunohistochemical examination of rat skeletal muscle during graft-versus-host disease (GVHD), a systemic immune reaction, was performed to investigate specific immune reactivities focusing on major histocompatibility complex (MHC) expression and inflammatory cell infiltration of skeletal muscle during a systemic immune reaction. MHC class II expression and inflammatory cell infiltration did not increase. MHC class I was expressed along the contour of muscle fibres, and most strongly expressed by the cells which were distributed throughout the endomysium and perimysium. Seventy-six percent of these MHC class I+ cells carried endothelial cell-markers, while 24% of them did not. The latter cells were revealed not to be inflammatory cells such as lymphocytes, granulocytes or macrophages when examined by immunostaining using several exudate-cell markers. Neither were they myosatellite cells because they were located outside the basement membrane. These results may be useful for considering animal models of inflammatory myopathies such as polymyositis and dermatomyositis.

Animals↗
PubMed1995

Immunohistochemical localization and biological significance of the phylogenically conserved thymus-brain antigen (UB-13 antigen) in skate, rat and human.

A monoclonal antibody (UB-13) originally raised against the brain of the skate (Raja kenojei, a cartilaginous-fish) was found to react with lymphoid and brain tissues from many species when examined immunohistochemically. In rat and human thymus, UB-13 antigen was observed to be closely associated with reticular tissue in the medulla and cortex. Interestingly, a few or several thymocytes were encircled by the UB-13-reactive reticular tissue. At 14 days gestation, rat thymus consisted mainly of reticular epithelial tissue, after which strong thymocyte production started. At this stage, some of the reticular tissue was heavily stained with UB-13. In the thymus tissues of the irradiated and recovering rats, where reduction and massive reproduction of thymocytes were observed, extensive UB-13 antigen expression localized on the reticular epithelial tissue, an observation which may support the thymocyte re-population. These findings suggest that the antigen recognized by UB-13 may be important for thymocyte proliferation and maturation. UB-13 antigen was found in the fibrous structure of the molecular and granular layer of the human cerebellum. Some glial cells were also stained strongly with UB-13 in the human cerebellar or cerebral grey and white matter. In rat, glial cells, especially astroglias, and the endothelial structure of blood vessels were stained strongly with UB-13. These findings suggest that UB-13 may be a useful monoclonal antibody for analysis of brain-lymphoid antigen in many species.

Adult↗
PubMed1995

[Effect of growth hormone and thyroxine on renal development in Snell pituitary dwarf mice].

To elucidate the effects of growth hormone (GH) and thyroxine (T4) on renal development, we biochemically and morphologically examined the renal tissue of Snell pituitary dwarf mice (dw/dw) at different developmental stages. Differences in DNA, RNA and insulin-like growth factor-1 (IGF-1) content between the dwarf and normal control mice first became apparent on the 10th day of age, and from this time that of dwarf mice showed no further increase in DNA and RNA content and decrease in IGF-1 content, whereas that of the normal control mice continued to increase. These findings indicated that GH and T4 may have effects on the renal development, and deficiency of these hormones to affect renal development from the 10th day of age.

Animals↗
PubMed1994

Analysis of cell surface antigens using anti-rat hepatocyte monoclonal antibodies, particularly HAM 1.

The expression of antigens on rat hepatocytes was examined by immunoelectron microscopy using monoclonal antibody HAM 1. The antigen recognized by HAM 1 was expressed mainly on both sinusoidal and bile-canalicular faces and only sparsely on the contiguous face. All rat hepatoma cell lines examined were intensely labeled with HAM 1, but poorly labeled with HAM 3, HAM 4, and HAM 5, as revealed by flow cytofluorometry and radioimmunoassay. Expression levels of HAM 1 antigen on the AH 44 hepatoma cell line similar to the degree seen in normal liver were demonstrated by radioimmunoassay. HAM 1 antigen was also expressed weakly on lymphocytes, thymocytes, and some bone marrow cells, but not on red blood cells, and differed from the MHC class I antigen recognized by HAM 2 and OX 18. Significant amounts of cell surface antigens recognized by all the monoclonal antibodies (HAM 1-HAM 5) were confirmed by radioimmunoassay on the cell surface of primary cultured hepatocytes. These results suggest that the rat hepatoma cell lines employed are different from normal hepatocytes, that primary cultured hepatocytes are more similar to normal hepatocytes in the degree of expression of their cell surface antigens, and that HAM 1 antigen appears to be a significant antigen on both normal and transformed hepatocytes.

Animals↗
PubMed1994

Changes in the distribution and intensity of alkaline phosphatase activity in rat lymph node and spleen cells after antigen stimulation.

We investigated the reaction of the popliteal lymph nodes (PLN) to the injection of two antigens, keyhole limpet hemocyanin (KLH) and lipopolysaccharide (LPS), into the footpads of rats, as well as the changes occurring in the PLN after allogeneic cell stimulation. Changes in alkaline phosphatase (ALP) activity of the lymph nodes were examined enzyme histochemically. Paralleling with PLN weight gain, increased ALP activity was observed in the medullary regions of the lymph nodes of stimulated rats. ALP reactivity in the stimulated lymph nodes was observed to be weak in the germinal centers and strong in the medullary regions. The spleens of rats subjected to systemic graft-vs.-host (GVH) reaction were examined in a similar fashion. The ALP-positive areas of the GVH spleens increased in size as compared with normal spleens. These positive areas of lymph node and spleen appear to correspond mainly to areas containing OX12-positive cells. These results suggest that enzyme-histochemical analysis of ALP activity together with immunohistochemical analysis of lymphocyte phenotypes may be a useful method for examining lymph node and spleen reactions to soluble and cellular antigens in rats.

Alkaline Phosphatase↗
PubMed1994

[Pyomyositis of iliopsoas muscle with infection of renal cyst: a case report].

We report a case of pyomyositis of iliopsoas muscle with infection of renal cyst. A 50-year-old woman was admitted to our hospital complaining of left lumbago, and we suspected that she had a left ureteral stone at first. Ultrasonogram and intravenous pyelography showed bilateral multilocular renal cyst and enlargement of the left iliopsoas muscle. Finally she was diagnosed with left pyomyositis of iliopsoas muscle with infection of renal cyst by ultrasonogram, computerized tomography scan and magnetic resonance imaging. She had no complaints after she had received antibiotic therapy for a week.

Bacterial Infections↗
PubMed1993

Immunohistochemical characterization of transplantable rat squamous cell carcinoma (FF-6) in skin and thymus.

FF-6 is a transplantable squamous cell carcinoma which originally arose in the facial skin of a DA rat. It was established after maintaining the tumor in the subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30 generations. When the soybean-sized original FF-6 tumor was transplanted subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized nodule within one month. After intraperitoneal transplantation of FF-6, it formed many nodules ranging from miliary to thumb-head size, which adhered and/or metastasized to many abdominal organs. When FF-6, cut into small pieces, was injected into the lower lip, the tumor grew bigger in situ, and metastasized to regional lymph nodes. Histologically, FF-6 was characterized as a well-differentiated squamous cell carcinoma, showing positive staining with anti-keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14 antibodies. This transplantable tumor may be useful for analyzing the mechanisms of proliferation and metastasis of squamous cell carcinoma in vivo, and the host defence mechanism in rats, as well as being a suitable model of human squamous cell carcinoma.

Animals↗
PubMed1992

Phagocytosis by the murine testicular TM4 Sertoli cell line in culture.

To investigate phagocytosis, an assay enabling flow cytometric analysis of single cells having internalized fluorescent carboxyl microspheres was employed. Greater than 80% of murine testicular Sertoli line (TM4) cells were found to phagocytose one or more microspheres within six hours and electron microscopy confirmed carboxyl microsphere internalization. This level was equivalent to that of a macrophage-like cell line and much greater than the levels of testicular Leydig (TM3) cells. Reducing extracellular calcium or using a calcium channel blocker profoundly inhibited phagocytosis suggesting that phagocytosis by Sertoli cells requires extracellular Ca++. Although follicular stimulating hormone, luteinizing hormone, and testosterone had no significant effects on Sertoli cell phagocytosis, insulin, epidermal growth factor, and hydrocortisone enhanced activity. In contrast, beta-endorphin and 8-bromoadenosine-cyclic monophosphate had an inhibitory effect. In contrast to augmenting macrophage phagocytosis, 1,25-(OH)2D3, interferon-gamma, prostaglandin E2, and lipopolysaccharides, had no apparent effect on that by Sertoli cells. Additionally, neither C3bi receptors (Mac-1 antigen) nor FcRII could be detected on Sertoli cells. In total, the findings demonstrated that the murine Sertoli line exhibits potent phagocytic function and suggest the regulation of this activity may differ from that in "professional" phagocytic cells.

8-Bromo Cyclic Adenosine Monophosphate↗