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Biomedical subjects

H Kudo

Publications and source records attributed to H Kudo.

At least 379 records · Page 21Linked to original sources

Cause of closed suction drainage tube obstruction and its prevention using a tube coated on the inside with a silicone gel drug delivery system.

In experimental and clinical studies we showed that obstruction of closed suction drainage tubes is often caused by clots. To prevent this we describe a tube coated on the inside with a silicone gel drug delivery system, which releases anticoagulant drugs. It prevents coagulation and liquefies blood clots present in the tube. This device should thus find application as a tube for continuous suction drainage systems.

Anticoagulants↗

Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats.

Keishi-bukuryo-gan (TJ-25) is a traditional Chinese herbal remedy containing five components: bark of Cinnamomum cassia, root of Paeonia lactiflora, seed of Prunus persica or P. persiba var. davidiana, carpophores of Poria cocos and root bark of Paeonia suffruticosa. This preparation has been used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and infertility. In the present study, the effects of TJ-25 on plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2), and on uterine wet weight and thymidine kinase (TK) activity were documented in immature rats. Long-term daily oral administration of TJ-25 (300 mg/kg) for 14 days decreased plasma levels of LH, FSH and E2 by 94%, 67% and 50%, respectively, compared to controls. Uterine wet weight and TK activity were reduced to 65% and 64% that of controls, respectively. Short-term effects of TJ-25 on E2 were also examined. Thirty hours after administration of E2 (1.0 micrograms/kg) alone, uterine wet weight and TK activity were elevated 2.4- and 21-fold, respectively, over controls. However, simultaneous administration of TJ-25 (three consecutive doses, every 12 h) with E2 reduced E2-induced increases in uterine wet weight and TK activity by 29% and 39%, respectively. Treatment with TJ-25 also enhanced LH-RH-induced increases in plasma LH and FSH levels 1.2- and 2.5-fold, respectively, as compared with controls. The results obtained in the present study indicate that TJ-25 may act as a LH-RH antagonist and/or as a weak anti-estrogen.

Administration, Oral↗

Imaging stretched single DNA molecules by pulsed-force-mode atomic force microscopy.

The effect of a surface water layer on DNA strands deposited on a substrate was studied by atomic force microscopy (AFM). DNA molecules were deposited and stretched on chemically modified glass coverslips by a molecular combing method. Lambda bacteriophage DNA molecules were aligned on the organosilane-modified substrate surfaces by chemical and physical adsorption during the molecular combing. The combed DNA molecules were observed in humidity-controlled air and in aqueous solutions by pulsed-force-mode AFM (PFM-AFM). Chemical modification of cantilevers with an Au-coated tip by organothiol compounds was also applied to DNA observation. Mapping adhesive forces in aqueous media was useful to discriminate chemically the DNA strands from the substrate surface. The results suggest that PFM-AFM can be used widely to image the stretched DNA molecules on the silane-modified substrates.

Adsorption↗

Immunohistochemical studies on the localization of cancer associated antigens DU-PAN-2 and CA19-9 in carcinomas of the digestive tract.

The immunohistochemical localization of DU-PAN-2 antigen and CA19-9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU-PAN-2 antigen and CA19-9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU-PAN-2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19-9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU-PAN-2 was observed, whereas diffuse staining for CA19-9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19-9, but not that of DU-PAN-2. These immunohistochemical studies showed that DU-PAN-2 antigen is expressed diffusely in most cases of adenocarcinoma of the pancreas and biliary tract and is more specific for adenocarcinomas of the pancreas and biliary tract than CA19-9.

Adenocarcinoma↗

Isotricha jalaludinii n. sp. found from the rumen of lesser mouse deer, Tragulus javanicus, in Malaysia.

Isotricha jalaludinii n. sp. found in the rumen of lesser mouse deer, Tragulus javanicus, in Malaysia was described and illustrated. This new species is characterized by the location and direction of the vestibulum, shape of the macronucleus, and absence of a dent at the vestibular opening. The presence of single peculiar isotrichid species in the rumen of mouse deer, which is recognized as one of the most primitive ruminants, suggests that the isotrichid ciliates similar to I. jalaludinii and Isotricha intestinalis were established at a fairly early period during the evolution of ruminants.

Animals↗

Correlation between histological differentiation and DNA-synthesizing enzymes in rat colorectal tumors induced with 1, 2-dimethylhydrazine.

Thymidylate synthase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Colorectal carcinogenesis induced with 1,2-dimethylhydrazine in rats enhanced mRNA expression levels of both enzymes, resulting in the increase of both enzyme activities and bromodeoxyuridine-immunoreactive S-phase cells. Poorly and well differentiated adenocarcinomas of the colorectum showed the relative elevation of activities of thymidylate synthase and thymidine kinase, respectively. These results indicate that the relationship between de novo and salvage pathways for pyrimidine nucleotide synthesis may depend on the histopathological grades of cell differentiation.

Animals↗

Effects of lentinan on colorectal carcinogenesis in mice with ulcerative colitis.

Lentinan; i.e., polysaccharides extracted from a kind of black mushroom shiitake, has been clinically applied as an antitumor and antimetastatic drug, and has been reported to prevent both chemical and viral carcinogenesis. It is known that lentinan affects the tumorous vascular system resulting in the induction of hemorrhagic necrosis which is dependent on T-cells in the tumor. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. In the present study, the additive treatment with lentinan in the azoxymethane-dextran sulfate sodium treated mice enhanced the colorectal high-grade dysplasia, though not significantly, and the splenic weight. This may show the proliferation of pathogenic splenic T cells resulting in a change for the worse of ulcerative colitis, anemia induced with hemorrhage and colorectal carcinogenesis; i.e., high-grade dysplasia of the mucosa and/or invasive adenocarcinomas of the colorectum. The present results may recommend chemoimmunotherapy while using lentinan, but not immunotherapy using lentinan alone, is indicated for the management of cancer patients.

Animals↗

Does macrophage-colony stimulating factor stimulate rat haematopoietic cells?

It is known that colony stimulating factors (CSFs) stimulate the myeloid cells of bone marrow and splenic cells in rodents. The effects of macrophage (M)-CSF on the activities of thymidylate synthase and thymidine kinase, involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively, in haematopoietic cells of bone marrow and spleen were investigated in rats. A single M-CSF injection did not elevate the mRNA expression levels of the enzymes in bone marrow cells 6 h after treatment, but it enhanced the splenic thymidylate synthase mRNA expression. M-CSF stimulated the splenic thymidylate synthase activity without an increase of the peripheral granulocytes. The effect of M-CSF on granulocytes is considered to be weak compared with that of granulocyte (G)-CSF, because of the indirect secretion of endogenous G-CSF from the cells with M-CSF receptors stimulated by exogenous M-CSF. Since M-CSF was able temporarily to lead progenitor cells from long G1-phase into S-phase, M-CSF might accelerate the anticancer effects when used together with anticancer agents.

Animals↗

Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.

BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.

Animals↗

Effects of a low dose leucovorin with 5-fluorouracil derivative on colorectal tumors induced with 1,2-dimethylhydrazine in rats.

Thymidylate synthase, which is a key enzyme involved in the de novo pathway for pyrimidine nucleotide synthesis, is inhibited by 5-fluorodeoxyuridine monophosphate, forming an inactive ternary complex with intracellular folate. We investigated the effect of a 5-fluorouracil derivative (UFT) with or without low dose leucovorin on the number of 5-fluorodeoxyuridine monophosphate binding sites, thymidine kinase activity and intracellular folate concentration in 1,2-dimethylhydrazine-induced rat colorectal carcinomas. A 10-day administration of UFT with or without leucovorin enhanced the thymidine kinase activity and the number of 5-fluorodeoxyuridine monophosphate binding sites, with an increase of thymidylate synthase mRNA expression. Thymidylate synthase inhibition was slightly increased as the intracellular folate concentration increased. These results indicate that thymidylate synthase inhibition increases when the intracellular folate is exogenously supplemented and maintained at an adequate concentration.

1,2-Dimethylhydrazine↗

Preventive effects of sulphasalazine on colorectal carcinogenesis in mice with ulcerative colitis.

Sulphasalazine has been used in the treatment of ulcerative colitis and is known to be a prodrug and split into sulphapyridine and 5-aminosalicylic acid by bacteria in the colon. An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis, which displays a recurrence-remission cycle on colorectal mucosa, i.e., the ulceration and regeneration periods of the colorectal mucosa. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. Additive treatment with sulphasalazine normalized the enlarged organs, i.e. liver, spleen and kidney and anemia and leucocytosis induced with 3% dextran sulfate sodium resulted in the reduction of tumorous regions with high-grade dysplasia.

Animals↗

Thermal effects on DNA synthesis in bone marrow cells of patients with acute myeloblastic leukemia.

It has been known that thymidylate synthetase (TS) and thymidine kinase (TK) are DNA-synthesizing enzymes via the de novo and salvage pathways, respectively, in pyrimidine metabolism, and an immunological method using a monoclonal antibody to bromodeoxyuridine (BrdU) is useful for the detection of S-phase cells. We investigated the effects of hyperthermia on DNA synthesis in bone marrow cells obtained from patients with acute myeloblastic leukemia. TK isozymes in bone marrow cells of patients with acute myeloblastic leukemia were separated into two types, i.e., fetal type isozyme in cytosolic cell fraction and adult type isozyme in mitochondrial cell fraction. Heating at over 43 degrees C as a hyperthermia markedly suppressed enzyme activity of fetal type TK isozyme and number of S-phase cells labelled with BrdU, but not activities of adult type TK isozyme and TS. These results indicate that hyperthermia may regulate the proliferation of S-phase cells by the suppression of salvage synthesis of DNA.

Bone Marrow↗

Suppression by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of preneoplastic mammary hyperplastic alveolar nodule formation in SHN virgin mice.

It is known that hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in mammary glands of mice. We examined the effect of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) on HAN formation in a high mammary tumour strain of SHN virgin mice. Oral administration of UFT for 5 months beginning at one month of age significantly reduced the number of HAN and DNA-synthesizing enzyme activities in the mammary glands. These results indicate that long-term administration of low dose UFT reduces the de novo and salvage synthesis of DNA and suppresses preneoplastic HAN.

Animals↗

Effects of danazol on DNA synthesis in submaxillary glands of male rats.

Danazol is an isoxazol derivative of the synthetic steroid, 17 alpha-ethinyltestosterone (ethisterone). Intragastric administration of danazol (10 mg/100 g body weight) markedly reduced plasma levels of luteinizing hormone and testosterone, and the number of S-phase cells labelled with bromodeoxyuridine (BrdU) in the submaxillary glands which were androgen-dependent in adult male rats. These results demonstrated that danazol might show a potency as antiandrogenic and/or antigonadotrophic agent.

Androgen Antagonists↗

Effects of oestrogen on mitochondrial thymidine kinase activity in the immature rat uterus.

Thymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway. High TK activity and the existence of cytosolic isozyme have consistently been observed in rapidly proliferating tissues. Oestrogen treatment induces the moderate increase of activities of mitochondrial TK and the fetal type TK isozyme in immature rat uterus. These results indicate that oestrogen induces the increase of uterine DNA synthesis in both cytosol and mitochondria in immature rats.

Animals↗

Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.

Animals↗

Topography of Alzheimer's neurofibrillary change distribution in myotonic dystrophy.

Histological changes that explain the mental symptoms of patients with myotonic dystrophy (MD) have not fully been demonstrated yet. Recently, the presence of Alzheimer's neurofibrillary changes (ANCs) in the brain have been reported in this disease. We studied the brain of a 61-year-old male with MD. The distribution of ANCs was investigated and mapped through careful histological examinations. The examinations disclosed that in MD, ANCs distributed along their preferential sites of the brain; a great number of ANCs were found in the parahippocampus, hippocampus, amygdaloid nucleus, fusiform gyrus, insula, and olfactory bulb, many in the nucleus basalis of Meynert, inferior temporal gyrus, hypothalamus, and brain stem, and a few in the cingulate, frontal and temporal gyri, neostriatum, and mammillary body. In the brain stem, ANCs were seen in the central gray, oculomotor nucleus, linear nucleus, substantia nigra, locus coeruleus, dorsal raphe nucleus, superior central nucleus, retriculotegmental nucleus, and reticular formation. From this result and the previous reports by others, it may be suggested that the presence of ANCs concentrated mostly in the limbic system is a regular and significant histological finding in the brain in MD. Therefore, this limbic lesion must be related to some of the mental symptoms unique to MD. In addition, diffuse and considerable neuronal atrophy and gliosis in the thalami in the absence of ANCs also may have played a causative role in some of the mental symptoms of the present case. Besides the more concentrated occurrence of ANCs within the limbic system, the minimal presence of senile plaques in the CNS may differentiate the brain in MD from that in Alzheimer-type dementia.

Adult↗