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Biomedical subjects

K Kitoh

Publications and source records attributed to K Kitoh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

Angiotensin II↗
PubMed2000

[ALL complicated by obstructive jaundice due to choledocholithiasis after unrelated bone marrow transplantation].

A 22-year-old man with acute lymphocytic leukemia underwent allogeneic bone marrow transplantation (BMT) from an unrelated donor in October 1996. In April 1997, he suddenly developed severe abdominal pain with nausea and vomiting. The diagnosis was obstructive jaundice associated with gallstones in the gallbladder and common bile duct. The patient underwent laparoscopic cholecystectomy and endoscopic removal of the stones in the common bile duct. The major component of the gallstones was bilirubinate calcium. Although the pathogenesis of gallstones after BMT remains unclear, several factors including impaired contractility of the gallbladder, hemolysis, changes in bile composition, and biliary tract infection may play important roles.

Adult↗
PubMed1999

Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle.

Described herein is the discovery of a novel series of antitumor sulfonamides targeting G1 phase of the cell cycle. Cell cycle control in G1 phase has attracted considerable attention in recent cancer research, because many of the important proteins involved in G1 progression or G1/S transition have been found to play a crucial role in proliferation, differentiation, transformation, and programmed cell death (apoptosis). We previously reported our first antitumor sulfonamide E7010 as a novel tubulin polymerization inhibitor. Interestingly enough, continuous research on structurally related compounds led us to the finding of another class of antitumor sulfonamides that block cell cycle progression of P388 murine leukemia cells in G1 phase, but not in M phase. Of the compounds examined, N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide (E7070) showed significant antitumor activity against HCT116 human colon carcinoma both in vitro (IC(50) 0.11 microg/mL in cell proliferation assay) and in vivo (not only growth suppression but also a marked reduction of tumor size in nude mice). Because of its promising efficacy against human tumor xenografts and its unique mode of action, E7070 is currently undergoing phase I clinical trials in European countries.

Animals↗
PubMed1999

Rapid development of hepatic metastasis with high incidence following orthotopic transplantation of murine colon 38 carcinoma as intact tissue in syngeneic C57BL/6 mice.

BACKGROUND AND OBJECTIVES: Orthotopic transplantation of human colon tumors was a useful method for producing hepatic metastasis in mice. In many cases, however, it took about 3 months for evaluation. We examined an in vivo model of hepatic metastasis for only 4 weeks by conducting orthotopic transplantation of murine Colon 38 tumor using intact tissue in syngeneic mice and determined the efficacy of chemotherapeutic agents against hepatic metastasis. METHODS: Twenty milligrams of tumor tissues were prepared from subcutaneously (s.c.) growing Colon 38 tumor and orthotopically transplanted on the cecum in C57BL/6 mice. Mice were autopsied about 4 weeks after transplantation. Metastases to various organs were detected macroscopically or histochemically and tumor invasion into the cecum was observed histochemically. In experimental chemotherapy, mice bearing orthotopically transplanted Colon 38 tumor were separated into three equal groups and were either treated with fluorouracil or cisplatin (CDDP), or untreated. Four weeks after transplantation, activities of both agents against local tumor growth and hepatic metastasis were evaluated. RESULTS: Macroscopic metastases to various organs including the liver, the lung, and the peritoneum were developed during days 28 to 32 after inoculation. The frequency of hepatic metastasis was 96% (N = 23). Histological examination indicated that the local tumor invaded various layers of the cecum and metastasized to the liver and lung hematogenously. In experimental chemotherapy with fluorouracil and CDDP, only fluorouracil decreased the incidence of mice with hepatic metastasis (2/8 cases), compared with vehicle treatment (7/8 cases) and the number of metastatic nodules in the liver (P = 0.016), although the inhibition against local growth of CDDP in T/C [45%; mean tumor weight of the test group (T) compared with that of the control group (C)] was similar to that of fluorouracil (53%). CONCLUSIONS: This model, with its rapid development of hepatic metastasis in high frequency, should be useful as a screening assay to find anti-metastatic agents for colorectal carcinoma.

Adenocarcinoma↗
PubMed1999

Method of lymphocytotoxic crossmatch test for feline renal transplantation.

The optimal condition for methods of lymphocytotoxic crossmatch test for feline renal transplantation was investigated. On separation of viable lymphocytes from whole blood, the best results were obtained when Ficoll-diatrizoate with 1.078 of a specific gravity at 20 degrees C was centrifuged with 800 x g for 30 min at 4 degrees C. A nylon wool column was used to separate T and B cells from lymphocyte fraction. The ratio of T cells in nylon wool effluent cells was 95%, while the ratio of B cells in adherent cells was 41%. Lymphocytotoxic crossmatch tests were performed by using the effluent cells as T cells and the adherent cells as B cells, at 37 degrees C (warm) and 4 degrees C (cold). The ratio of B cells in adherent cells was low, however, the result was utilized as a matching test before transplantation by combining with the T cell result. The trypan blue stain method made it easier than the eosin stain method to distinguish living and dead cells. The lymphocytotoxic crossmatch tests were performed on 15 pairs of healthy cats, and only one pair showed doubtful positive against anti-B cell cold antibodies. During acute rejection after renal transplantation in two pairs which were negative on any anti-lymphocyte antibodies before the transplantation, the anti-T cell warm antibodies became positive in both pairs, and the anti-T cell cold antibodies became positive on one of the two pairs.

Animals↗
PubMed1999

Establishment of a quantitative mouse dorsal air sac model and its application to evaluate a new angiogenesis inhibitor.

We have developed an improved mouse dorsal air sac model for quantifying in vivo tumor-induced angiogenesis. In our improved model, tumor angiogenesis is determined by measuring the blood volume in an area of skin held in contact with a tumor cell-containing chamber, using 51Cr-labeled red blood cells (RBC). The blood volume induced by murine B16-BL6 melanoma cells increased linearly with the cell number in the range from 2 x 10(5) to 5 x 10(6). Ten of 11 human tumor cell lines examined induced a significant increment in blood volume. For three representative human tumor cell lines (A549, WiDr. and HT1080 cells) that showed different angiogenic potencies, the levels of vascular endothelial growth factor (VEGF) produced by the tumor cells cultured under conditions of hypoxia and high cell density were correlated with the degree of in vivo angiogenesis. Using the improved model, it was confirmed that TNP-470, a well-known inhibitor, and borrelidin, an antibiotic from Streptomyces rochei, significantly inhibited the WiDr cell-induced angiogenesis. Borrelidin also inhibited spontaneous lung metastasis of B16-BL6 melanoma at the same dose that inhibited angiogenesis. Our results suggest that the improved mouse dorsal air sac model can be used for simple and quantitative measurement of tumor-induced angiogenesis and its inhibition.

Angiogenesis Inhibitors↗
PubMed1998

Comparison of laboratory test results before and after surgical removal of heartworms in dogs with vena caval syndrome.

OBJECTIVE: To compare results of laboratory tests in dogs with vena caval syndrome before and after surgical removal of heartworms. DESIGN: Longitudinal uncontrolled clinical trial. ANIMALS: 51 dogs with vena caval syndrome. PROCEDURE: Heartworms were removed from the area of the tricuspid valve and pulmonary arteries via venotomy and by use of flexible alligator forceps. Blood samples were obtained before and 10 days after removal of heartworms. Red and white blood cell counts were determined, using an automated cell counter. Biochemical tests were performed, using a dry chemical method. RESULTS: 45 dogs survived the procedure, and 6 died or were euthanatized after surgical treatment. After surgery, RBC count and total protein, albumin, calcium, and sodium concentrations increased, and total bilirubin, ammonia, BUN, creatinine, uric acid, and potassium concentrations decreased in dogs that survived. Creatine kinase, L-lactate dehydrogenase, and amylase activities decreased, whereas alkaline phosphatase and gamma-glutamyltransferase activities and total cholesterol concentration increased. Alanine transaminase activity decreased in 27 dogs but increased in 3 dogs. Changes in test results in dogs that did not survive. Significant differences were found in RBC count, gamma-glutamyltransferase activity, and total protein, total cholesterol, BUN, and total bilirubin concentrations before and after removal of heartworms. CLINICAL IMPLICATIONS: Hepatic and renal functions improve rapidly after surgical removal of heartworms, presumably because general and pulmonary circulation is normalized. However, cholestasis may develop, and dogs that survive may need additional treatment to preserve hepatic function.

Anemia↗
PubMed1998

Involvement of dendritic cell response to resistance of stomach carcinogenesis caused by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

The involvement of immune response in the resistance of chemically induced stomach cancer was studied in a resistant rat strain (Buffalo) and a sensitive rat strain (ACI). Groups of 10 male Buffalo and ACI rats, 6 weeks of age, were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/l) for 14 days. Total RNA was isolated from the stomach pyloric mucosa from five rats, and cDNA was prepared with reverse transcriptase. Tissue sections of the stomach pyloric mucosa from five rats were stained with antibodies recognizing molecules expressed by various immune cells. Reverse transcription-PCR (RT-PCR), competitive RT-PCR, and Northern blot demonstrated that the expression of MHC class II group genes [MHC class II, MHC class II-associated invariant chain (Ii), CD4 and IgM (B cell marker)], MHC class I group genes (MHC class I and CD8), B7-1 (costimulator on dendritic cells), and CD28 (receptor to B7 on T cells) in the pyloric mucosa was elevated by MNNG in both rat strains but was elevated to a 4-7-fold greater extent in Buffalo rats than in ACI rats. These genes were scarcely expressed in control rats. Histochemical antibody staining after MNNG exposure showed a greater number of cells stained with monoclonal antibody to Ii, OX-62 (dendritic cell marker), and ED-1 (dendritic cell and macrophage common marker) in the interstitial tissue of the pyloric mucosa of Buffalo rats compared with ACI rats. Cell proliferation, as measured by 5-bromo-2-deoxyuridine (BrdUrd)-labeling indices, revealed the presence of BrdUrd-labeled cells only among epithelial cells in the proliferative zone; cells in the interstitial tissue were not labeled with BrdUrd. The results suggest the involvement of dendritic cell response in the resistance to the MNNG induction of stomach carcinogenesis in rats.

Animals↗
PubMed1998

Pathologic findings in dogs with shock induced by intravenous administration of heartworm extract.

OBJECTIVE: To examine pathologic findings in dogs with shock induced by IV administration of heartworm (HW) extract. ANIMALS: 22 mixed-breed adult dogs. PROCEDURES: Heartworm extract was administered IV, and pathologic changes in dogs that died or were euthanatized at 24 hours were examined. RESULTS: The most severe lesions observed during initial collapse were centralobular congestion in the liver, hemorrhage and edema in the gallbladder wall, and congestion and hemorrhage in mucous membranes of the gastrointestinal tract. These findings disappeared with recovery from collapse. Hyalinization of venous walls of the liver and cardiac muscle were observed in dogs that died during initial collapse. Focal coagulation necrosis in hepatic cells was seen in dogs that were euthanatized at 24 hours. One dog with profuse bloody diarrhea that died during secondary collapse had severe hemorrhage in mucous membranes of the large intestine. CONCLUSION: Heartworm extract appeared to contain some substances constricting hepatosplanchnic vessels and some toxic substances that injured the smooth muscle of venous walls, cardiac muscle, and hepatic cells directly or indirectly. CLINICAL RELEVANCE: The shock-inducing substances in HW extract may have an important role in the pathophysiologic mechanism of HW disease, and investigation of them may contribute to prevention of the shock reaction attributable to microfilaricide and adulticide use.

Anaphylaxis↗
PubMed1997

Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin.

E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonami de), an orally active sulfonamide antitumor agent that is currently in a Phase I clinical trial, showed rather consistent growth-inhibitory activities against a panel of 26 human tumor cell lines (IC50 = 0.06-0.8 microg/ml), in contrast to vincristine (VCR; IC50 = 0.0002-0.04 microg/ml), 5-fluorouracil (IC50 = 0.2-30 microg/ml), Adriamycin (IC50 = 0.002-0.7 microg/ml), mitomycin C (IC50 = 0.007-3 microg/ml), 1-beta-D-arabinofuranoxylcytosine (IC50 = 0.005 to >30 microg/ml), camptothecin (IC50 = 0.002-0.4 microg/ml), and cisplatin (IC50 = 0.5-20 microg/ml). It caused a dose-dependent increase in the percentage of mitotic cells in parallel with a decrease in cell proliferation, like VCR. It also showed a dose-dependent inhibition of tubulin polymerization, which correlated well with the cell growth-inhibitory activity. 14C-labeled E7010 bound to purified tubulin, and this binding was inhibited by colchicine but not by VCR. However, its binding properties were different from those of colchicine, as well as those of VCR. E7010 was active against two kinds of VCR-resistant P388 cell lines, one of which showed multidrug resistance due to the overexpression of P-glycoprotein (resistant to Taxol), and the other did not show multidrug resistance (sensitive to Taxol). Furthermore, four E7010-resistant P388 cell lines showed no cross-resistance to VCR, a different pattern of resistance to podophyllotoxin, and collateral sensitivity to Taxol. Therefore, E7010 is a novel tubulin-binding agent that has a wider antitumor spectrum than VCR and has different properties from those of VCR or Taxol.

Aminophenols↗
PubMed1997

Reciprocal control of colon-specific sulfomucin and sialosyl-Tn antigen expression in human colorectal neoplasia.

Histochemical reports claim that sulfomucins decrease and sialylated mucins increase during colon carcinogenesis. We examined the expression of colon-specific sulfomucins and sialosyl Tn antigen (STN) in normal small intestine, normal colorectal mucosa and colorectal tumours at different stages of progression immunohistochemically, using MAb 91.9H specific for colonic sulfomucins and MAb TKH-2 for STN. No expression of sulfomucins recognized by MAb 91.9H was found in normal small intestine, whereas STN staining was pronounced. The converse was the case in normal colorectal mucosa. Sulfomucins were still found in adenomas, but the amounts decreased with depth of invasion in cancers (P < 0.001). In contrast, no STN could be detected in benign lesions, but staining became increasingly evident with invasion (P < 0.001). This reciprocal control of expression of colon-specific sulfomucins and STN evident in tumour progression indicates that the mucous phenotype shifts from the colonic to the small intestinal type.

Adenoma↗
PubMed1997

Ascorbic acid and reducing agents regulate the fates and functions of S-nitrosothiols.

Although S-nitrosoglutathione (GS-NO) and other S-nitrosothiols (RS-NO) exhibit activity attributable to nitric oxide (NO), the dynamic aspects of their metabolism remain to be elucidated. To determine the fates and functions of RS-NO, the stability of GS-NO was analyzed in plasma, and various fractions of liver and kidney. GS-NO was fairly stable under physiological conditions in plasma and buffer solutions. However, GS-NO was rapidly decomposed in the presence of either homogenates of rat liver and kidney or their supernatant fractions. The ability of the supernatants to decompose GS-NO remained unchanged after the removal of proteins and large molecular weight compounds. Physiological levels of reducing agents, such as reduced glutathione (GSH), ascorbic acid (AsA), and cysteine, also enhanced the decomposition of RS-NO; the order of their potency was AsA > cysteine >GSH. Considering their intra-cellular concentrations and potency, AsA might principally be responsible for the enhanced decomposition of GS-NO. NO, GS-NO, and related RS-NO inhibited the respiration of Ehrlich ascites tumor cells. The inhibitory effect of GS-NO was enhanced by the reducing agents (cysteine>AsA>GSH). Intravenously administered GS-NO exhibited a depressor action through some ascorbic acid enhancable mechanism. Thus, the metabolism and biological function of GS-NO and related RS-NO might be affected by AsA and other reducing agents.

Animals↗
PubMed1997

Sparse distribution of hepatocyte growth factor-producing cells inside hepatocellular foci in rats treated with hepatocarcinogens.

The distribution of hepatocyte growth factor (HGF)-synthesizing cells in rat liver during development of glutathione S-transferase P form (GST-P)-positive nodules after diethylnitrosamine initiation followed by promotion with 2-acetylaminofluorene plus partial hepatectomy (PH) was investigated using in situ hybridization. HGF-producing cells were non-parenchymal in nature, and were suspected to be mainly of Kupffer type. They were mostly located outside GST-P-positive lesions, in the surrounding parenchyma. In the oval cell proliferation phase 1 week after PH, they increased and they were mainly localized around the portal triads. It is concluded that HGF is directly involved in an endogenous paracrine growth pathway controlling proliferation in oval cells and in normal, but not GST-P-positive, hepatocytes.

2-Acetylaminofluorene↗
PubMed1997

Efficacy of monotherapy with benazepril, an angiotensin converting enzyme inhibitor, in dogs with naturally acquired chronic mitral insufficiency.

Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional classes II and III) congestive heart failure caused from mitral insufficiency (MI). There were no significant changes in clinical signs, electrocardiogram findings, radiographical observations and plasma biochemical results in 11 dogs treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased, and mean scores of heart failure signs, such as activity, exercise tolerance, cough and respiratory effort, were significantly improved. No dog displays signs suggesting systemic hypotension. One dog died suddenly on the 26th day of treatment with BP. This dog had good vigor and appetite till the evening before the death, and cough and exercise tolerance had been gradually improving. The heart rate and ECG parameters of BP treated dogs did not change significantly, but length of long axis of the heart decreased. In plasma biochemical tests, plasma urea nitrogen (UN) levels did not change significantly, and plasma creatinine (CRE) levels increased slightly within the normal ranges during BP trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE levels, but had normal general condition and other biochemical results. Plasma ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP treatment. It is concluded that BP monotherapy was efficacious at least in dogs with relatively low grade congestive heart failure caused by MI.

Administration, Oral↗
PubMed1997

Comparison of laboratory data in dogs with heartworm caval syndrome surviving and nonsurviving after surgical treatment.

Laboratory data in 47 dogs with caval syndrome (CS) surviving after surgical HW removal compared with those in 15 dogs with CS which died after the treatment. The number of HWs removed in surviving dogs was significantly greater than in nonsurviving dogs. The Ht value was significantly higher in nonsurviving dogs than in surviving dogs. Plasma enzyme activities ranged widely from normal to extremely high levels, and there were no significant differences in plasma enzyme activities between the surviving and nonsurviving dogs. Serum total protein, and plasma triglyceride, creatinine, glucose, calcium, sodium (Na) and chloride (Cl) levels were much similar between the HW-free and surviving dogs, but significantly different between the HW-free and nonsurviving dogs. Plasma urea nitrogen, uric acid and potassium levels were higher, and plasma Na and Cl levels were lower in nonsurviving dogs than in surviving dogs.

Animals↗
PubMed1997

Borrelidin is an angiogenesis inhibitor; disruption of angiogenic capillary vessels in a rat aorta matrix culture model.

Borrelidin, an antibiotic from Streptomyces rochei, was found to be an angiogenesis inhibitor in a rat aorta matrix culture model which forms capillary vessels in vitro. Borrelidin strongly inhibited capillary tube formation with a 50%-inhibitory concentration value of 0.8 nM, and decreased the number of capillary tubes within 24 hours when added after maturation of tube formation. Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells.

Animals↗
PubMed1996

Inconsistent association of Epstein-Barr virus with CD56 (NCAM)-positive angiocentric lymphoma occuring in sites other than the upper and lower respiratory tract.

We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)-cell lineage with a surface CD3-CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein-Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs) and immunohistology for EBV-determined nuclear antigen-2 (EBNA-2) and latent membrane protein-1 (LMP-1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP-1 in the cytoplasm of tumour cells without EBNA-2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER-positive cases either clonally or biclonally. It was revealed by re-evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV-positive tumours, the EBV-negative tumours stood out because of their remarkably uniform 'blastoid' appearance, and could be grouped as blastic NK-cell lymphoma. The relationship of the EBV-positive cases with nasal NK-cell tumours has yet to be clarified.

Adult↗