Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 343 records · Page 19Linked to original sources

PubMed1994

Structural studies on the tri- and tetrasaccharides isolated from porcine intestinal heparin and characterization of heparinase/heparitinases using them as substrates.

We prepared a series of oligosaccharides from porcine intestinal heparin after extensive digestion with a mixture of Flavobacterium heparinase as well as heparitinases I and II. Previously, we reported the structures of the two glycoserines derived from the carbohydrate-protein linkage region [Sugahara et al., J. Biol. Chem., 267, 1528-1533 (1992)] and three tetrasaccharides derived from the antithrombin III-binding site [Yamada et al., J. Biol. Chem., 268, 4780-4787 (1993)]. In this study, we determined the structures of 10 other tetrasaccharides and a trisaccharide by enzymatic digestion, fast atom bombardment mass spectrometry and 500-MHz 1H NMR spectroscopy. These tetrasaccharides share the common disulphated structure, delta HexA alpha 1-4GlcN(N-sulphate)alpha 1-4IdoA(2-sulphate)alpha 1-4GlcN (where HexA is hexuronic acid and IdoA is L-iduronic acid), and their structural variations are based upon the positions of additional sulphate groups. Eight among the 10 have never been isolated as discrete structures. The structure of the trisaccharide is GlcN(N-sulphate)alpha 1-4IdoA(2-sulphate) alpha 1-4GlcN(N,6-disulphate) and is derived from the non-reducing terminus of heparin chains. This structure may represent the terminus of a biosynthetically formed native heparin chain or a newly formed non-reducing terminus exposed by a tissue endo-beta-glucuronidase which may be involved in the intracellular post-synthetic fragmentation of macromolecular heparin. The 11 structures characterized in the present study and 6 additional tetrasaccharides were used to investigate the substrate specificities of heparinase, as well as heparitinases I and II. The results indicate that modification of the adjacent glucosamine on the reducing side of the disaccharide cleavage site influences the enzymatic action of the lyases, whereas the adjacent uronic acid on the non-reducing side is not recognized by these enzymes.

Animals↗

PubMed1994

Different incidence of loss of heterozygosity on chromosome 16q between intraductal papilloma and intracystic papillary carcinoma of the breast.

Loss of heterozygosity (LOH) on chromosome 16q was examined in DNA isolated from 11 intraductal papillomas and 12 intracystic papillary adenocarcinomas of the breast. Such LOH was detected in 8 (67%) out of 12 intracystic papillary adenocarcinomas, and in 7 (64%) of 11 of these adenocarcinomas of low grade atypia (Grade 1), whereas it was not detected in 11 intraductal papillomas. Therefore, inactivation of tumor-suppressor genes on chromosome 16q was suggested to be involved in acquisition of malignant phenotype rather than in tumorigenesis in mammary gland epithelial cell. Examination of LOH on 16q should be helpful for differential diagnosis of intracystic papillary tumors.

Adenocarcinoma, Papillary↗

PubMed1994

Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast.

Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo, sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.

Base Sequence↗

PubMed1994

Chemopreventive effects of beta-carotene, alpha-tocopherol and five naturally occurring antioxidants on initiation of hepatocarcinogenesis by 2-amino-3-methylimidazo[4,5-f]quinoline in the rat.

Inhibitory effects of naturally occurring antioxidants on the initiation stage of hepatocarcinogenesis were studied. Group 1 rats were given a diet containing beta-carotene (beta-CT, 0.02%), alpha-tocopherol (alpha-TP, 1.5%), glutathione (GLT, 5%), vanillin (VNL, 1%), quercetin (QCT, 1%) or ellagic acid (ELA, 1%), or 3 doses of diallyl sulfide (DAS, 200 mg/kg, i.g.) over an 8-day period. On day 7, the animals received a single dose of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ, 100 mg/kg, i.g.), 12 h after two-thirds partial hepatectomy for initiation and 2 weeks thereafter, were placed on promotion regimen comprising phenobarbital (0.05% in diet) and a single dose of D-galactosamine (100 mg/kg, i.p.). Groups 2 and 3 were treated as described for Group 1, but without test material or IQ, respectively. Survivors were killed at week 11 and antioxidant influence was assessed by comparing values for preneoplastic glutathione S-transferase placental form-positive (GST-P+) foci between Groups 1 and 2. All lesions larger than 70 microns in diameter consisting of approximately 5 cells in cross section were counted. Numbers of GST-P+ foci/cm2 in Group 1 were: beta-CT, 7.99; alpha-TP, 8.21; GLT, 9.71; DAS, 10.37; VNL, 10.57; QCT, 11.1; ELA, 12.5 (n = 11-15). All, except ELA, showed a significant decrease as compared with the Group 2 value of 14.54 (n = 15). Only beta-CT showed a significant decrease for the area value. This is the first report to show that beta-CT, alpha-TP, GLT, DAS, VNL, QCT exert inhibitory effects on initiation of hepatocarcinogenesis by the food carcinogen IQ, suggesting that these antioxidants might find application as chemopreventive agents. Furthermore, the current protocol proved practical for the assessment of chemopreventive agents within 11 weeks, a relatively short period.

Allyl Compounds↗

PubMed1994

Immunohistochemical demonstration of intestinal-type alkaline phosphatase in stomach tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

A polyclonal antibody against rat intestinal-type alkaline phosphatase (I-ALP) was generated and proven to be applicable immunohistochemically to paraffin-embedded sections. Expression of I-ALP in normal tissues, intestinal metaplasia and stomach tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) animals were given drinking water containing 100 micrograms/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all stomach tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal-type tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I-ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I-ALP was also detected in the normal stomach, limited to the striated cell borders of absorptive cells of the upper one-fourth of intestinal metaplastic glands. I-ALP may thus be a useful marker for stomach tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No stomach tumors consisting mainly of intestinal-type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.

Adenocarcinoma↗

PubMed1994

Parvovirus B19-associated haemophagocytic syndrome with prominent neutrophilia.

We describe a patient with both haemophagocytic syndrome and acute myocarditis probably associated with parvovirus B19 infection. The patient had a marked neutrophilia instead of neutropenia more usually observed in virus-associated haemophagocytic syndrome (VAHS). Endogenous serum concentrations of macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-alpha (TNF-alpha) were higher than normal, suggesting that these cytokines may be involved in the genesis of the observed syndrome.

Acute Disease↗

PubMed1994

Malignant progression of adenomyoepithelial adenosis of the breast.

A case of breast tumor is described, which consisted of dense and uniform proliferation of ducts and lobules composed of both epithelial and myoepithelial cells and in which multiple foci of adenocarcinoma were observed. The tumor surrounding the carcinoma foci was identified as 'adenomyoepithelial adenosis'. Adenomyoepithelial adenosis was not monoclonal by clonal analysis, but revealed a relatively high labeling index for proliferating cell nuclear antigen by immunohistochemistry. Although it was still undetermined whether adenomyoepithelial adenosis is a non-clonal nonneoplastic lesion or a biclonal neoplastic one, the lesion was shown to reveal high proliferative activity in both glandular epithelial and myoepithelial cells and was considered to be prone to progress to obvious carcinoma.

Adenocarcinoma↗

PubMed1994

Role of protein phosphorylation in EPO-mediated early signal transduction: analysis in the EPO-reactive cell line ELM-I-1 transfected with a c-fos-enhancer/promoter-luciferase reporter gene.

To investigate the role of protein phosphorylation in the early phase of EPO-mediated signal transduction, we EPO-stimulated a murine erythroid cell line ELM-I-1 transformed by plasmids comprised of the c-fos enhancer/promoter linked to the luciferase gene. Using this reporter gene system, we previously showed that EPO-induced activation of the c-fos promoter can be detected rapidly and sensitively as an elevation of cellular luciferase activity. In this study, we first examined the role of protein tyrosine phosphorylation. The tyrosine phosphatase inhibitor orthovanadate not only induced luciferase activity by itself but enhanced the action of EPO. On the other hand, the tyrosine kinase inhibitors erbstatin and herbimycin suppressed the effect of EPO. Next, the role of protein kinase C (PKC) in the EPO response was assessed. The PKC activator phorbol myristate acetate (PMA) not only induced luciferase activity by itself but enhanced the action of Epo. On the other hand, the PKC inhibitor 1-(5-isoquinolynyl-sulfonyl)-2-methylpiperazine (H7) suppressed the effect of Epo and PMA, whereas a nonspecific protein kinase inhibitor, N-(2-Guanidinoethyl)-5-Isoquinolinesulfornamine (HA1004) inhibited the action of neither Epo nor PMA. Another known PKC inhibitor staurosporine (STSP) did not inhibit but rather enhanced the effect of Epo. This action of STSP was blocked by H7 but not by HA1004. These results suggest that the EPO-mediated early signal transduction pathway leading to c-fos expression involves protein-tyrosine phosphorylation, is modulated by tyrosine phosphatase activity and is positively regulated by PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

A new system that analyzes erythropoietin-mediated early signal transduction: transfection of the c-fos enhancer.promoter-luciferase gene into a murine erythroid cell line.

Erythropoietin (Epo) exerts its effects by binding specific receptors on the surface of reactive cells. However, the signal transduction system after binding has not been well described. To develop a system to analyze the steps of signal transduction, we transfected the human c-fos-enhancer/promoter linked with the Photinus pyralis luciferase gene (pfosluc2) into a murine erythroleukemia cell line ELM-I-1, in which we previously showed that c-fos mRNA is rapidly induced upon Epo-stimulation. A stable transfectant was obtained. The cells transfected with pfosluc2 were stimulated with Epo and luciferase activity in the cells was measured as light intensity. The light intensity integrated for 2 min (LI2.0) was 3202 +/- 80 unit/1.5 x 10(5) cells before stimulation. This increased up to 5869 +/- 321 unit/1.5 x 10(5) cells by incubating the cells with 5 U/ml Epo for 2 h. After Epo stimulation, light intensity began to increase at 30 min, reached a peak (about 1.8 times the basal level) at 120 min, and then gradually dropped. The effect of Epo was dose-dependent; significant action occurred at as low as 0.5 U/ml, with a maximum at 5 U/ml. A similar response was observed when the cells were stimulated with interleukin-3 (IL-3) although the response was apparently lower than that with Epo. It was also found that IL-3 had an additive action with Epo on c-fos activity in this system. Thus, the above method was proven to be simple, rapid and sensitive enough to use to determine the early phase of signal transduction of Epo.

Animals↗

PubMed1994

Orientational micro-Raman spectroscopy on hydroxyapatite single crystals and human enamel crystallites.

Single crystals of synthetic hydroxyapatite have been examined by orientational micro-Raman spectroscopy. The observed Raman bands include the PO4(3-)/OH-internal and external modes over the spectral range from 180 to 3600 cm-1. The Raman-active symmetry tensors (A, E1, and E2) of crystal-class C6 have been assigned to these bands. Intensities of the Raman bands are invariant to the orientation of the a- or b-axis of a single crystal, but depend solely on the c-axis orientation. Changes in the spectral profile thus reflect changes in the c-axis orientation, which, with respect to the known excitation/observation coordinates, can be determined through the angular dependencies of Raman bands due to A and E2 symmetries. The useful bands are those of the PO4(3-)v4 vibrational mode, which contains relatively well-defined bands due to E2 (581 cm-1) and A (593 cm-1) symmetries. A preliminary Raman study on crystallites near the intact outer surface of human enamel has also been carried out. Strong orientational dependencies similar to those of hydroxyapatite single crystals have been observed among the bands in enamel spectra. This suggests that the crystallites in the region investigated are highly oriented. The results were consistent with an averaged orientation of the crystallite c-axis being perpendicular to the outer surface.

Crystallography↗

PubMed1994

[Accumulation of gene alterations and progression of breast cancer].

A number of gene alterations have been detected in human breast cancer, and their clinicopathological implications have been investigated. Amplification of the c-erb B-2 gene and point mutations of the p53 gene are shown to be associated with biological aggressiveness of cancer cells, whereas loss of heterozygosity on chromosome 16q is suggested to be associated with acquirement of malignant phenotype. Because these gene alterations are accumulated frequently even at the preinvasive stage, the genotype as well as phenotype of breast cancer appears to have been determined mostly relatively soon after tumorigenesis.

Breast Neoplasms↗

PubMed1994

Double burst stimulation with submaximal current.

The present study evaluated responses to double burst stimulation (DBS) at supramaximal and submaximal currents in 30 adult patients. Usually, DBS is applied with supramaximal stimulation, but this may be quite uncomfortable for the awake patient. Therefore, the authors investigated whether it is possible to obtain an accurate assessment of significant residual neuromuscular blockade if the stimulus current is reduced to 30 mA. In all patients, neuromuscular response to DBS three three (DBS3.3), DBS three two (DBS3.2) and train-of-four (TOF) stimulation at supramaximal and/or submaximal currents was recorded using a mechanomyograph, and the ratios of the fourth to the first twitch (T4/T1) induced by TOF stimulation at supramaximal current, and the height of the second response to the first (D2/D1) induced by DBS at 30 mA and supramaximal current were calculated. The relations between control T4/T1 ratios determined by supramaximal TOF stimulation and D2/D1 ratios determined by supramaximal DBS3.3 and submaximal DBS3.3 were Y = 0.99X + 0.08 and Y = 1.01X + 0.04, respectively, and there was no statistical difference between the two regression lines. The same relation between T4/T1 ratios and D2/D1 ratios by DBS3.2 were Y = 0.69X + 0.05 and Y = 0.72X + 0.02, respectively, and there was no significant difference. It is concluded that evaluation of the response to DBS at 30 mA has the same reliability as evaluation with supramaximal current.

Adult↗

PubMed1994

[Patients acceptance of immediate breast reconstruction after subcutaneous mastectomy in breast disease].

Most profound emotional impact for the women with breast carcinoma is experienced as loss of femininity as a result of surgical mutilation. From this point of view, the recommendation for reconstructive surgery provide the amelioration to patient's anxiety. Two hundred women with breast carcinoma including huge nonepithelial malignant and/or benign tumors who adopted the breast reconstruction were treated during a 13-year period in 1982-1994 at NCCH. The breast reconstruction was mainly created by latissmus dorsi musculocutaneous (LDMC) flap in one sitting (modified mastectomy plus simultaneous reconstruction). Thirty patients treated with subcutaneous mastectomy (conserving the nipple-areolar complex) among them, were followed by deepithelialized LDMC flap without implant as the procedure of choice in early carcinoma located in lateral half at a distance of at least 4-5 cm from the areola and in huge benign tumors. Although one patient was dissatisfied with ischemia of LDMC flap, this approach was safe, simple, and possible to produce the patient's satisfaction. There was a positive effect on life style and on sexual, social or work relationships.

Adolescent↗

PubMed1994

[Successful treatment of acute promyelocytic leukemia in a pregnant woman by using all-trans retinoic acid].

A 34-year-old woman was admitted because of pancytopenia with DIC in the 28th week of pregnancy. Bone marrow aspirate demonstrated 81.2% abnormal cells which showed Auer bodies and faggot formation. Chromosomal analysis demonstrated an abnormality, t (15; 17). The patient was diagnosed as having acute promyelocytic leukemia (APL) and started to receive treatment with all-trans retinoic acid (ATRA) 70 mg/body/day per os. She had a cesarean section and gave birth to a female infant in the 29th week of pregnancy. An increase of WBC counts was observed on the 9th hospital day, then chemotherapy with anti-cancer agents was performed additionally. Complete remission was achieved on the 27th hospital day. Management of pregnant patients with APL could be improved by using ATRA instead of conventional combinations of cytotoxic agents.

Adult↗

PubMed1994

Leiomyosarcoma of the pancreas: report of a case diagnosed by fine needle aspiration biopsy.

We present a case of pancreatic leiomyosarcoma with liver metastasis diagnosed by liver tumor biopsy. A 66-year-old man had a pancreatic tumor and hepatic tumors, which were hypoechoic and mixed echoic on ultrasonography, respectively. They were stained in enhanced computed tomography and angiography. A fine needle aspiration biopsy of the liver tumor was performed, and the pathological examination of the biopsied specimen suggested the tumor cells to have originated from smooth muscle. Under a diagnosis of pancreatic leiomyosarcoma with liver metastasis, the patient was treated with several anticancer agents. The tumor, however, spread to multiple organs and he dies of the disease two years nine months after the start of treatment. The diagnosis of pancreatic leiomyosarcoma was confirmed by autopsy.

Aged↗

PubMed1994

[Adult T cell leukemia with cytomegalovirus associated hemophagocytic syndrome].

A 59-year-old woman, diagnosed as adult T-cell leukemia (ATL), was admitted because of fever and disturbance of consciousness. Peripheral blood examination demonstrated leukopenia and anemia, and subsequently thrombocytopenia. Bone marrow aspiration showed the increase of mature histiocytes with hemophagocytosis and a diagnosis of hemophagocytic syndrome (HPS) was established. She died due to respiratory failure on the eighth hospital day. Autopsy histological examination revealed systemic cytomegalovirus (CMV) infection with CMV pneumonia, and also demonstrated the findings of HPS in bone marrow, lymph nodes, and spleen. This case was considered as virus associated hemophagocytic syndrome (VAHS) developed by CMV infection. CMV is one of the causative viruses of VAHS and the opportunistic infection. In the patient with ATL in the immunodeficiency state, VAHS accompanied with opportunistic infection might be one of the causes of pancytopenia.

Cytomegalovirus Infections↗

PubMed1994

[A new neuromuscular transmission monitor (TOF Guard): the rationale behind the method and its clinical usefulness].

TOF Guard is one of the latest developments in the field of neuromuscular monitoring equipment. This system uses a miniature acceleration transducer (a piezo-electric ceramic wafer is used), simply fastened to the thumb with tape. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. In this study, authors assessed the accuracy of this system in clinical use, comparing with the force transducer method (Myograph 2000). The result showed that there was a very close positive correlation between the values of T1, TOF ratio and posttetanic count simultaneously measured by both methods. The coefficient of correlation was 0.96, and its significance level was P < 0.001. From the clinical view point, it is concluded that TOF Guard is very useful because of its accuracy and because the equipment is easy to handle, compact and of low price as a neuromuscular monitoring system for routine anesthesia.

Adult↗

PubMed1993

Endometrial assessment by transabdominal ultrasonography in postmenopausal women.

We evaluated the usefulness of transabdominal ultrasonography (TAS) for endometrial abnormalities in postmenopausal women. A total of 232 postmenopausal women were examined by TAS and endometrial sampling. Abnormal findings, including endometrial hyperplasia, atypical hyperplasia and endometrial cancer, were noted in 0.7% (1/41) of sonographically measured endometrium < 2 mm and in 15.4% (14/91) of measurements > or = 2 mm. Endometrial cancer was found in 5.9% in the postmenopausal bleeding group (n = 85) and in 1.4% in the symptom-free group (n = 147). With one exception, all endometrial abnormalities were in endometrial thickness > or = 2 mm. We conclude that TAS has limitations as a technique but is useful in deciding which postmenopausal women require endometrial biopsy.

Adult↗