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Biomedical subjects

H Oguchi

Publications and source records attributed to H Oguchi.

At least 19 recordsLinked to original sources

The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with the human protein.

A mouse thyroid-specific enhancer-binding protein (T/EBP) gene and its flanking regions have been cloned and completely sequenced. The gene consists of 2 exons and exhibits high similarity (83-97%) to the rat sequence throughout the coding region and including an intron and up to 1.3 kbp upstream to the ATG initiation codon. A cDNA clone encoding human T/EBP has been also isolated and sequenced. Comparison of the deduced amino acid sequence of T/EBP revealed an extensive identity of 98% between mouse and the human protein.

Amino Acid Sequence

Long-term histological evaluation of hydroxyapatite ceramics in humans.

We have investigated the interface between bone and hydroxyapatite (HA) chronically implanted in man. By light microscopy, HA appeared to bind directly to bone without intervening fibrous tissue. By transmission electron microscopy, two patterns were noted: (1) HA either bound directly to bone; or (2) electron-dense material intervened between HA and bone. The orientation of bone collagen fibres likewise showed two patterns: (1) collagen fibres were oriented parallel to the HA; or (2) the fibres were aligned perpendicularly. We have observed similar binding properties of HA to the jaw bone of humans in vivo and in vitro.

Adult

In situ localization of transforming growth factor-beta 1 mRNA in the rat kidney with Masugi nephritis.

Masugi nephritis was induced in rats by the administration of nephrotoxic duck serum and, in their kidneys, the distributions of transforming growth factor-beta 1 (TGF-beta 1) mRNA, TGF-beta 1, and macrophage antigenic marker were investigated. Kidney specimens were obtained at 3, 7, and 14 days after the injection. By in situ hybridization, TGF-beta 1 mRNA was found to be localized in the cells of mesangial region from the early stage of nephritis. By the immunohistochemical stainings, TGF-beta 1 was found to be localized in the cells of distal convoluted tubulus throughout the experiments and the macrophage antigenic marker was found to be localized in the occasional cells which were different from that contained TGF-beta 1 mRNA. Our data indicate that TGF-beta 1 mRNA is expressed by the resident glomerular cells and not by the migrating macrophages in rat kidney with Masugi nephritis.

Animals

Radiation-induced hypoplasia of the teeth and mandible. A case report.

Hypoplasia of the mandible and teeth is reported in a 4-year-old boy who had cystic hygroma. At age 7 months he had been treated with 60Co-gamma-radiation (24 Gy to the head and neck, 45 Gy to the mediastinum) followed by surgery. Panoramic and periapical radiographs showed hypoplasia of the roots of the primary canines, molars, and permanent teeth and no evidence of tooth germs. The patient was followed up to age 13 years.

Bone Development

Sensitisation of human ovarian carcinoma cells to cis-diamminedichloroplatinum (II) by amphotericin B in vitro and in vivo.

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.

Amphotericin B

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.

Antigens, Tumor-Associated, Carbohydrate

Epitope analysis of SPan-1 and DUPAN-2 using synthesized glycoconjugates sialyllact-N-fucopentaose II and sialyllact-N-tetraose.

Epitope analysis of SPan-1 and DUPAN-2 was compared with that of CA19-9 using the synthesized glycoconjugate sialyllacto-N-fucopentaose II (SLF II, sialyl-Lewis(a)) and its precursor, sialyllact-N-tetraose (LSTa, sialyl-Lewis(c)), conjugated to human serum albumin. The CA19-9 and DUPAN-2 assay systems specifically recognized SLF II and LSTa, respectively. The SPan-1 assay system recognized both SLF II and LSTa, although the reactivity with the former was far stronger than that with the latter. These results were, in general, compatible with those obtained from assaying these markers in the sera of two pancreatic cancer patients with definite Lewis-negative phenotype and in the sera of 39 CA19-9-negative pancreatic cancer patients. In conclusion, DUPAN-2 is the precursor of CA19-9 and is accumulated in the sera of pancreatic cancer patients with Lewis-negative phenotype and SPan-1 has an advantage over CA19-9 in the diagnosis of patients with Lewis-negative phenotype, although both markers have almost the same sensitivity for this malignancy.

Antibodies, Monoclonal

Potentiation of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) by amphotericin B in BALB/c nude mice bearing human ovarian carcinoma cells.

Human ovarian carcinoma cells (HRA) were sensitized to cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) 1.2-, 2.1- and 3.4-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4, and 10.8 microM, respectively. Moreover, the intracellular accumulation of platinum after 2-h exposure to CBDCA was increased significantly by AMB treatment. For estimating the enhancing effect of AMB on CBDCA cytotoxicity in vivo, we prepared HRA cell-inoculated nude mice. Ascites was evident 7 to 9 days after intraperitoneal (i.p.) inoculation of HRA cells, and the mice died of intraabdominal carcinomatosis 11 to 14 days (mean survival time (MST): 12.0 +/- 1.0 days) after inoculation. Treatment with AMB (2.0 mg/kg) alone increased the MST by only 1.2 days. Simultaneous treatment with CBDCA (12 or 15 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CBDCA alone. Maximal MST (38.5 days) was obtained by treatment with 15 mg/kg CBDCA plus 2.0 mg/kg AMB, whereas the MST with 15 mg/kg CBDCA alone was 15.8 days. A drug accumulation study demonstrated that platinum accumulation in tumor tissues after i.p. treatment with CBDCA and AMB in tumor-bearing nude mice was increased significantly compared to treatment with CBDCA alone. These findings indicate that intraperitoneal combination chemotherapy with CBDCA and AMB is useful in nude mice with advanced ovarian carcinoma.

Amphotericin B

Synthesis of multivalent beta-lactosyl clusters as potential tumor metastasis inhibitors.

A beta-lactosyl residue was linked to the amino groups of L-lysyl-L-lysine through spacer arms of three different lengths (C2, C4, and C9) to give trivalent beta-lactosyl clusters in order to increase the inhibitory activity of the beta-lactosyl group against tumor cell colonization. Thus, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-2,3, 6-tri-O-acetyl-glucopyranosyl trichloroacetimidate was treated with methyl or benzyl hydroxyethanoate, methyl or benzyl 4-hydroxybutanoate, and methyl 9-hydroxynonanoate, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate to give the corresponding beta-lactosides. These were coupled to L-lysyl-L-lysine, after conversion to the N-hydroxysuccinimide esters, to yield the corresponding trivalent beta-lactosyl-L-lysyl-L-lysine conjugates in good yields. The beta-lactosyl group with a C4 spacer arm was also coupled similarly to poly(L-lysine) (M(r) 3800) to form a polyvalent beta-lactosyl cluster. Coinjection of the trivalent (with C2 and C4 spacer arms) and polyvalent beta-lactosyl clusters with the highly metastatic B16 murine melanoma cells inhibited the formation of lung colonies in C57/BL mice, whereas the trivalent cluster with a C9 spacer arm displayed no activity.

Animals

A newly synthesized bifunctional inhibitor, W-77, enhances adriamycin activity against human ovarian carcinoma cells.

A newly synthesized calmodulin antagonist, (S)-P-(2-aminoethyloxy)-N-[2-(4-benzyloxy-carbonylpiperazinyl++ +)-1-(P-methoxybenzyl)ethyl]-N-methylbenzenesulfonamide dihydrochloride (W-77), acts as a calcium-independent uncompetitive antagonist which binds to glutathione-S-transferase (GST). We purified GST from human placenta using drug affinity chromatography on a column of W-77 coupled with Sepharose 6B and demonstrated that W-77 bound to GST. A spectrophotometric assay also showed that W-77 inhibited GST activity. We prepared Adriamycin-resistant and -sensitive cells from human ovarian serous cystadenocarcinomas. Immunoblot analysis revealed that GST expression was increased in the Adriamycin-resistant cells. We also purified GST from Adriamycin-resistant cells and found that W-77 bound to the GST obtained from these ovarian carcinoma cells. Adriamycin resistance was partially overcome by the addition of W-77 (10 microM) to the cultured cells. In addition, we investigated the effect of W-77 on P-glycoprotein. Northern blot analysis revealed MDR1 gene expression in Adriamycin-resistant cells. Although W-77 was less potent in increasing the intracellular Adriamycin content than verapamil, it was more effective in overcoming Adriamycin resistance. These results suggest that W-77 enhances the antitumor activity of Adriamycin by inhibiting both GST and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem

Clinical remission criteria for epithelial carcinoma of the ovary.

After primary cytoreductive surgery 188 patients with epithelial ovarian cancer were treated with combination chemotherapy between 1986 and 1989 in the Tokai Ovarian Tumor Study Group. Clinical remission criteria were set in this study and patients were examined to determine if they were in remission or not. Forty-seven cases (25%) had no remission and 85.9% of them died within 20 months after primary surgery. Fifty-seven cases (30.3%) had a remission and a subsequent recurrence. Eighty-four cases (44.7%) had no recurrence and all are currently alive. Independent remission factors by multivariate analysis were higher stage (P = 0.018), clear-cell carcinoma (P = 0.0048), larger maximum residual tumor (P = 0.0023), and PVB therapy (P = 0.026). Independent recurrence factors were higher stage (P = 0.0012), serous cystadenocarcinoma (P = 0.0001), clear-cell carcinoma (P = 0.00409), and PVB therapy (P = 0.0499). A significantly high remission rate and low recurrence rate was achieved using PVB therapy. This criteria has value for the treatment of epithelial ovarian carcinoma. The disease-free survival rate after clinical remission was the same as that after a negative second-look laparotomy, which implies that a second-look laparotomy may be unnecessary in the management of epithelial carcinoma of the ovary.

Adenocarcinoma

Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function.

Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2)%; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function.

Adult

Stiffening of connective tissue in elderly diabetic patients: relevance to diabetic nephropathy and oxidative stress.

Limited joint mobility seen in diabetes mellitus is thought to be the result of stiffening of periarticular connective tissue, which is presumably derived from increased cross-linking of collagen related to advanced glycation end products. In this study the extent of the stiffening of connective tissue was measured by the passive extension angle of the metacarpophalangeal joints in 205 elderly diabetic patients. Association with diabetic nephropathy, with which advanced glycation end products have recently been demonstrated to increase, and metabolic abnormalities were also considered. The angle of the metacarpophalangeal joints was significantly correlated with age (r = -0.24, p < 0.01), and was significantly smaller in men than in women (p < 0.01). The angle demonstrated a decrease in association with diabetic retinopathy and nephropathy, and only the association with nephropathy was significant (p < 0.05). The angle was weakly, but significantly, correlated with serum thiobarbituric acid reactants as a measure of lipid peroxides (r = -0.15, p < 0.05), triglyceride (r = -0.20, p < 0.01) and HDL cholesterol (r = 0.19, p < 0.01), but not with blood glucose (r = 0.02), HbA1c (r = 0.06) or duration of diabetes (r = -0.05). In addition, the angle in 14 non-diabetic patients on haemodialysis was significantly (p < 0.05) smaller than that in age- and sex-matched normal subjects. Thus, it was indicated that the stiffening of connective tissue was associated with diabetic nephropathy, serum lipid peroxide and dyslipidaemia. Stiffening of connective tissue seems to be more affected by oxidative stress than non-enzymatic glycation per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria

Pregnancy and successful delivery in a patient with triple heart valve prosthesis.

A 42-year-old patient had a history of rheumatic fever in childhood. At 37 years of age, she underwent a triple heart valve replacement; thereafter, she was followed with the administration of warfarin and methyldigoxin. Her third pregnancy occurred with the last menstruation on 12 March 1990. At the 30th gestational week, she was admitted to the Nagoya University Hospital for the control of anticoagulation and rest. She delivered by cesarean section a healthy male infant weighing 2070 g at 34 weeks of gestation. The post-operative course was uneventful. This report shows that a patient with a three heart valve prosthesis tolerated pregnancy well under intense medical supervision.

Adult

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Adult

Pharmacokinetics of temocapril and enalapril in patients with various degrees of renal insufficiency.

Temocapril is a novel ACE inhibitor that is cleared via dual excretion routes in humans. Borderline or mildly hypertensive patients with normal renal function [group 1, creatinine clearance (CLCR) > 70 ml/min (4.2 L/h), n = 12], moderate renal impairment [group 2, CLCR 30 to 70 ml/min (1.8 to 4.2 L/h), n = 12] or severe renal impairment [group 3, CLCR < 30 ml/min (1.8 L/h), n = 12] received a single oral dose of either temocapril 1 mg (n = 6, each group) or enalapril 5mg (n = 6, each group). These 2 drugs gave similar values for the area under the plasma concentration-time curve (AUC) of the active diacids. The maximum plasma concentration of enalapril diacid was increased 2- and 6-fold in moderate and severe renal impairment, respectively, whereas that of temocapril diacid was not altered. The AUC of enalapril diacid increased 13-fold at CLCR values < 30 ml/min, but that of temocapril diacid increased only 2-fold. The duration of plasma ACE inhibition due to enalapril was greatly prolonged by the impairment of renal function, whereas that due to temocapril was affected very little. Urinary recovery of temocapril diacid was decreased markedly in patients with severe renal dysfunction, most probably because the diacid was excreted through the biliary route. On the other hand, urinary recovery of enalapril diacid remained fairly high even in patients with severe renal impairment, because of extremely high plasma diacid concentrations resulting from the lack of biliary excretion. These observations suggest that temocapril is beneficial in the treatment of hypertension in patients with severely impaired renal function.

Adult