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Biomedical subjects

T Kudo

Publications and source records attributed to T Kudo.

At least 289 records · Page 16Linked to original sources

Hepatic oxygen supply, energy charge, and histological findings in dogs with portal vein arterialization.

Hepatic oxygen supply, energy charge (EC), and histology were examined comparatively in dogs with portal vein anastomosis (PVA group), and PA in addition to PVA (PA group). The PVA group showed a lower level of hepatic oxygen supply than those of the PA group throughout the experimental period, and also showed decreases of adenosine triphosphate (ATP) and EC level after blood perfusion. In contrast, the oxygen supply and consumption were stable in the PA group. A temporary fall of ATP level was followed by recovery to the preperfusion level in the PA group. Histological examination indicated the collapse of hepatic cords with granular and vacuolar degeneration in only the PVA group. These findings suggested that PA, when supplemented to PVA, is an available technique for preventing hepatic failure caused by ischemic conditions.

Adenosine Triphosphatases↗

Gestational thyrotoxicosis manifesting as wernicke encephalopathy: a case report.

The thyroid gland is physiologically stimulated in normal early pregnancy. This stimulated thyroid function is occasionally termed "gestational transient thyrotoxicosis". The cause of this thyrotoxicosis has been clarified to closely it associate with human chorionic gonadotropin (hCG). We encountered a pregnant patient with hyperemesis and thyrotoxicosis, who manifested symptoms of Wernicke encephalopathy. Although her serum hCG concentration transiently increased in accordance with the thyrotoxicosis, it was within normal limits for the gestational week. Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy. This case suggests that pregnant patients with hyperemesis should undergo careful endocrinological and neurological evaluations.

Adult↗

A case of leiomyosarcoma of the sphenoid sinus.

A 43-year-old man with a primary leiomyosarcoma of the left sphenoid sinus is presented. To our knowledge, this is an unusual case of leiomyosarcoma, which has never been reported in the literature. Accurate and safe diagnosis was obtained by an endonasal endoscopic approach with minimal tissue invasion.

Adult↗

Enzyme-histochemical demonstration of the intramural lymphatic network in the monkey jejunum.

The structural organization of the intramural lymphatic networks in the jejunum of the Japanese monkey (Macaca fuscata) was studied by an enzyme-histochemical method using whole-mount preparations of tissue layers. A distinction between the lymphatics and the blood vessels was made by light microscopy using 5'-nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) double staining. In each tissue specimen, the reaction product for 5'-Nase activity was localized in the lymphatic vessels, whereas that for ALPase activity was restricted to blood vessels. The mucosal layer exhibited an irregular network of tubular lymphatics connecting to the central lymphatics in the villi. The submucosal layer revealed a horizontal mesh-like network consisting of tubulo-saccular lymphatics. A dense maze-like network of lymphatics was distributed throughout the myenteric layer. The lymphatic networks were independent of the blood vessels. The present results indicate the usefulness of the enzyme-histochemistry of whole-mount preparations of the laminar layers for demonstration of the structure and distribution of the lymphatic system in the intestinal wall.

5'-Nucleotidase↗

Analysis of mother-to-infant transmission of hepatitis C virus: quasispecies nature and buoyant densities of maternal virus populations.

Mother-to-infant transmission of hepatitis C virus (HCV) was analyzed by sequencing of viral RNA and semiquantitative polymerase chain reaction following ultracentrifugation of maternal sera. In two mother-infant pairs, the hypervariable region 1 (HVR1) and carboxyl terminus of envelope 1 (E1) were sequenced. Both viral sequences in the infants were less diverse than those of their mothers. Although the E1 sequences were almost identical in each mother-infant pair, the HVR1 sequences of the infants were related, but not identical, to those of the mothers. Serial examinations of one infant revealed that the HVR1 nucleotide sequence did not change from 10 days to 3 months of age. In six mothers with uninfected infants, all of the dense fractions of sera contained significant amounts of HCV RNA, whereas in six mothers with infected infants, only two of those fractions contained significant amounts of HCV RNA. These results indicate that the strains of HCV detected in the infants were not dominant in the mothers, but were still transmissible to the infants. As dense fractions are known to contain antibody-bound HCV particles, maternal antibodies against HCV may inhibit viral transmission.

Amino Acid Sequence↗

[Cisplatin/5-fluorouracil intraperitoneal administration superior to intravenous administration for liver metastases of colonic carcinoma].

A 28-year-old female underwent sigmoidectomy for sigmoid colon cancer with peritoneal seeding. One month later, a solitary metastasis was found in S3 of the liver. After CDDP/5-FU intravenous chemotherapy, another metastasis appeared in S7. Intravenous administration showed PD. But the metastatic tumors shrank and became inobservable by CT after the 1st round of CDDP/5-FU intraperitoneal chemotherapy, and S7 tumor could not be identified after the 2nd round. Many previous reports demonstrated the concentration of cytotoxic drug in intraperitoneal administration was much higher than in intravenous administration. Theoretically, intraperitoneal chemotherapy is superior to intravenous chemotherapy for the prevention and treatment of liver metastases. This case demonstrated this hypothesis was right. We think adjuvant intraperitoneal chemotherapy should be re-considered for the prevention of the liver metastases of gastrointestinal cancers.

Adenocarcinoma↗

Placenta growth factor is abundantly expressed in human cervical squamous cell carcinoma.

Tumor angiogenesis is essential for solid tumor growth. The object of this study was to investigate the presence of newly identified angiogenic factor, placenta growth factor (P1GF) in human cervical cancers. The expression of P1GF mRNA was assessed by RT-PCR in 29 patients with cervical cancer. Fifteen out of 29 cervical cancers expressed a certain level of P1GF mRNA. In addition, the expression levels of P1GF mRNA in squamous cell carcinomas were significantly higher than those in adenocarcinomas. There was no correlation between the expression of P1GF mRNA and FIGO stage. These results indicate that the expression of P1GF may be implicated in the promotion of angiogenesis in human cervical squamous cell carcinomas, but not in human cervical adenocarcinomas.

Carcinoma, Squamous Cell↗

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.

Animals↗

Noninvasive assessment of myocardial viability by positron emission tomography with 11C acetate in patients with old myocardial infarction. Usefulness of low-dose dobutamine infusion.

BACKGROUND: When patients with severely depressed left ventricular function are treated, it is crucial to know in advance how much functional recovery is expected from coronary revascularization. METHODS AND RESULTS: We compared the results of 11C acetate positron emission tomography (PET) with dobutamine infusion with changes in regional wall motion evaluated by left ventriculography in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but viable myocardium (group A, n = 13) was separated from nonviable myocardium (group B, n = 15) by echocardiographic assessments of regional wall motion before and after successful coronary revascularization. 11C acetate PET was performed to characterize normalized myocardial blood flow and oxidative metabolism (the clearance rate constant, k mono). While the baseline k monos of the infarct areas of the two groups were different with overlap, the responses to dobutamine infusion were directionally different. In addition, relative perfusion by 11C acetate PET could predict recovery of left ventricular function as well as or better than dobutamine 11C acetate kinetics. The extent of the increase in k monos of the infarct area with dobutamine infusion correlated well (P < .01) with the degree of the increase in the percentage of systolic segment shortening in the infarct area (left ventriculography) after coronary revascularization. CONCLUSIONS: 11C acetate PET with dobutamine infusion can predict not only the reversibility of dysfunctioning myocardium after coronary revascularization but also the extent of improvement of regional wall motion in patients with old Q-wave infarction.

Acetates↗

MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 10(7) LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials.

Animals↗

Molecular genetic analysis of the human Lewis histo-blood group system. II. Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals.

The Lewis histo-blood group system comprises two major antigens, Lewis a and Lewis b. The Lewis b antigen is a product of two fucosyltransferases, the alpha(1,3/1,4)fucosyltransferase (Lewis enzyme; Fuc-TIII) encoded by the Lewis gene and an alpha(1,2)fucosyltransferase which is not required for synthesis of Lewis a antigen. An enzyme responsible for secreting ABH antigens into body secretions (secretor enzyme) is also one of alpha(1,2)fucosyltransferases. A candidate gene encoding secretor enzyme Sec2 gene was recently cloned by Rouquier, S., Lowe, J. B., Kelly, R. J., Fertitta, A. L., Lennon, G. G., and Giorgi, D. ((1995) J. Biol. Chem. 270, 4632-4639) and Kelly, R. J., Rouquier, S., Giorgi, D., Lennon, G. G., and Lowe, J. B. ((1995) J. Biol. Chem. 270, 4640-4649) who demonstrated a G428A nonsense mutation (Trp143 to terminal codon) in Sec2 of nonsecretors. However, the G428A nonsense mutation discovered in the Sec2 gene of nonsecretors in an ethnic group other than Japanese was not found in any of 45 Japanese nonsecretors, whereas one Filipino who had been erroneously registered as a Japanese possessed the G428A mutation heterozygously. In order to explore the Sec2 gene of a Japanese population, we performed a molecular genetic analysis of the Sec2 gene on 226 Japanese individuals, 21 in a family study and 205 in a random sampling study. We discovered two novel mutations in the Sec2 gene, an A385T missense mutation (Ile129 to Phe) that results in inactivation of Sec2-encoded alpha(1,2)fucosyltransferase and a C357T silent mutation which is irrelevant to amino acid substitution, in Japanese nonsecretors. The analysis of Japanese individuals using the polymerase chain reaction-restriction fragment length polymorphism method found three alleles in the Sec2 gene, the first having no mutation, the second having a C357T mutation, and the third having both C357T and A385T mutations, which we designated as Se1, Se2, and sej, respectively. Among 226 Japanese individuals, 40 having a Le(a+b-) phenotype and 5 having a Le(a-b-) nonsecretor phenotype were homozygous for sej/sej, whereas 149 having a Le(a-b+) phenotype and 32 having a Le(a-b-)-secretor phenotype possessed at least one Se1 or Se2. The frequencies of occurrence of Se1, Se2, and sej among 410 alleles examined in a random sample of 205 Japanese individuals were 15, 46, and 39%, respectively, indicating a rather wide distribution of the sej allele in the Japanese population. The results show that the Sec2 gene really encodes the secretor enzyme alpha(1,2)fucosyltransferase and indicate that a ethnic group-specific nonsense or missense point mutation in the Sec2 gene determines nonsecretor status. The phylogenic aspect and biological significance of the Se and Le genes are discussed.

Amino Acid Sequence↗

Characterization of malate dehydrogenase from deep-sea psychrophilic Vibrio sp. strain no. 5710 and cloning of its gene.

A metabolic key enzyme malate dehydrogenase (MDH) was purified from a deep-sea psychrophilic bacterium, Vibrio sp. strain no. 5710. The enzyme displayed an optimal activity shifted toward lower temperature and a pronounced heat lability. A gene encoding this enzyme was isolated and cloned. Recombinant Escherichia coli cells harboring the isolated clone expressed MDH activity with temperature stability identical to that of the parental psychrophile. Nucleotide sequencing of the gene revealed that its primary sequence was similar to that of a mesophile E. coli MDH (78% amino acid identity), for which the three-dimensional structure is known. The enzyme is thus suitable for the analysis of molecular adaptations to low temperatures.

Adaptation, Physiological↗

Alteration of extracellular matrix in dilated cardiomyopathic hamster heart.

The purpose of this study was to characterize the collagen in hereditary dilated cardiomyopathic hamster hearts, and to examine the participation of the collagen in the occurrence and progression of cardiomyopathy. BIO 53.58 hamsters (5, 10, 20 weeks old) were used as the model of dilated cardiomyopathy. Flb hamsters were used as controls. The collagen content was almost constant at any age in the Flb hamsters, but increased with age in BIO 53.58 hamsters. Type III collagen increased significantly in BIO 53.58 hamsters at 10 weeks. The acetic acid solubility of collagen decreased in BIO 53.58 hamsters as the fibrosis progressed, but was unchanged in controls. Reducible crosslinks showed a tendency to decrease progressively in BIO 53.58 hamsters. There were no differences between Flb and BIO 53.58 hamsters at 5 weeks, but its expression in BIO 53.58 hamsters at 10 and 20 weeks of age increased compared to Flb controls. These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is rich in type III collagen. In the later phase, the matrix resembles that of hard tissues, whose collagen is mainly of type I collagen and is insoluble. These data suggest that the increased collagen synthesis may impair the cardiac function in the development of cardiomyopathy.

Animals↗

Genetic evidence for the Lewis enzyme, which synthesizes type-1 Lewis antigens in colon tissue, and intracellular localization of the enzyme.

To determine whether the Lewis enzyme responsible for the Lewis blood type antigens on erythrocytes synthesizes the Lewis antigens on normal cells and cancer cells in colon tissue, we performed genotyping of the Lewis gene by the PCR-RFLP method and by immunohistochemical staining of Lewis antigens and the Lewis enzyme with specific monoclonal antibodies (mAbs) in colon tissues obtained from 100 colon cancer patients. Five of the 100 patients were identified as homozygotes for the mutant Lewis gene, i.e., the le/le genotype that cannot encode functional Lewis enzyme. The cells in both the normal and cancerous regions of colon tissue from these five le/le patients were completely devoid of staining with mAbs against Lewis antigens with the type 1 chain, i.e., Lewis a, Lewis b, and sialyl Lewis a. In contrast, the cells in cancerous regions of the colon tissue of the 95 patients with the Le/Le or Le/le genotype positively stained with all three mAbs, anti-Lewis a, anti-Lewis b, and anti-sialyl Lewis a. The cells in the cancerous regions of the colon tissue of the five le/le patients stained with DU-PAN-2 mAb, whose recognizing epitope is known to be sialyl Lewis c, a precursor structure of sialyl Lewis a. By immunohistochemical staining with FTA 1-16 mAb, which is directed at the human Lewis enzyme, we were able to demonstrate for the first time that the enzyme is localized in the Golgi area of the colon epithelial cells of patients with the Le/Le or Le/le genotype. No staining was observed in the Golgi area of the cells of the patients with the le/le genotype. From these results, we conclude that individuals with the Le/Le or Le/le genotype possess a functional Lewis enzyme synthesizing fucosylated type-1 Lewis antigens in the Golgi apparatus of the colon epithelial cells, but that individuals with the le/le genotype are devoid of the Lewis enzyme in the Golgi apparatus, resulting in an inability to synthesize Lewis antigens with the type-1 chain, and that it is inappropriate to use CA19-9, whose antigenic epitope is defined as sialyl Lewis a, as a tumor marker in patients with the le/le genotype.

Antibodies, Monoclonal↗

Enhancement of anticoagulant action by warfarin-benzbromarone interaction.

To investigate the interaction between warfarin potassium and benzbromarone, administration of benzbromarone to patients receiving long-term treatment with both drugs was discontinued for 1 week and then resumed, and the resulting changes in the coagulation system were examined. Thrombotest value, activity of coagulation factors II and VIII, concentration of protein induced by vitamin K absence or antagonist-II (PIVKA-II), total plasma concentration of warfarin, and free warfarin concentration were measured during the period of concurrent administration of the two drugs, 1 week after discontinuation of benzbromarone, and after resumption of benzbromarone administration. After administration of benzbromarone had been discontinued for 1 week, the thrombotest value and factor II activity rose significantly whereas PIVKA-II activity dropped significantly compared with corresponding levels before discontinuation, but these parameters tended to revert to the previously maintained levels after resumption of benzbromarone treatment. Activity of the vitamin K-independent factor VIII displayed almost no changes, however. Total plasma warfarin concentration also decreased significantly, and free warfarin concentration was nearly unchanged. These results verified that the anticoagulant action of warfarin is enhanced by concurrent administration of benzbromarone. Accordingly, adequate consideration must be devoted to the prevention of grave hemorrhagic tendencies when these two drugs are administered concurrently.

Aged↗