Biomedical subjects

H Kohno

Publications and source records attributed to H Kohno.

At least 127 records · Page 7Linked to original sources

PubMed1998

Levels of soluble Fas in patients with myocarditis, heart failure of unknown origin, and in healthy volunteers.

This study showed that serum levels of sFas were elevated in patients with myocarditis, and that this elevation was correlated with sIL-2R level as a marker of T-cell activation. Therefore, sFas levels may be associated with T-cell activation in patients with myocarditis, and elevation of sFas may inhibit apoptosis in activated T cells, leading to persistent cell-mediated destruction of myocytes in myocarditis.

Adult↗

PubMed1998

Suppression of cell proliferation and the expression of a bcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by interferon-alpha.

A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/abl-2 splice junction. When the KT-1 cells were cultured with interferon (IFN)-alpha or IFN-gamma, the growth of the cells were dose-dependently suppressed. IFN-alpha and IFN-gamma exerted synergistic suppressive effects on the growth of KT-1 cells. Furthermore, IFN-alpha suppressed the expression of the bcr-abl fusion gene in KT-1 cells, and induced G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line should be a valuable tool for studying the molecular mechanism of the suppression of Ph1 clone cells from CML by IFN.

Apoptosis↗

PubMed1998

Modulation of endothelin and nitric oxide: a rational approach to improve canine hepatic microcirculation.

ET receptor blocker (TAK-044) and NO donor (FK409) were used to improve the hepatic microcirculation following ischemia-reperfusion injury. In the first experiment (60 minutes of ischemia), 15 dogs were divided into three groups: group A (control), saline; group B, TAK 5 mg/kg; and group C, FK 0.4 mg/kg. In the second experiment (90 minutes of ischemia), 38 dogs were divided into six groups that underwent 90 minutes of hepatic ischemia followed by reperfusion: group I (control), saline only; group II, TAK 5 mg/kg and FK 3.2 mg/kg; group III, TAK 5 mg/kg and FK 0.4 mg/kg; group IV, TAK 5 mg/kg; group V, FK 0.4 mg/kg; and group VI, FK3.2 mg/kg. All drugs were administered through the portal vein. Following 60 minutes of ischemia, both FK and TAK produced significant improvement in hepatic microcirculation and enzymatic status when compared with the control group. After 90 minutes of ischemia, low doses of FK and TAK significantly improved hepatic microcirculation and reduced portal pressure following reperfusion in group III compared with group I. Leakage of hepatic enzymes was prevented and tissue injury score was significantly lower in group III. In group VI, early protection was obtained to some extent; however, blood pressure was reduced significantly following reperfusion compared with group I. In contrast, hepatocellular function deteriorated and the tissue injury score was higher in group II animals. TAK pretreatment with low doses of FK provided the best protection for the hepatic microcirculation in ischemia-reperfusion injury of the liver.

Animals↗

PubMed1998

Prognostic factors and rational approach in the treatment of submucosal cancer of the stomach.

In early gastric cancer, lymph node metastasis is known to be a prognostic factor. A retrospective study of 134 patients with submucosal gastric cancer (SMGC) who had undergone gastrectomy with lymph node dissection was performed to evaluate the prognostic factors and indication of postoperative chemotherapy. Five-year disease-free survival rate for 121 patients without nodal metastasis was 100% with (n = 62) or without postoperative chemotherapy (n = 59). On the other hand, it was 72.9% for 13 patients with nodal metastases, although all patients had undergone D2 or D3 resection and received postoperative chemotherapy. Tumor recurrence occurred only in three patients (n = 3) with alpha-fetoprotein (AFP) producing cancer and lymph node metastasis. Multivariate analysis with the Cox's proportional hazard model revealed AFP positivity to be a new independent prognostic factor in addition to lymph node metastasis in the patients with SMGC. Our findings suggest that routine use of postoperative chemotherapy does not appear rational for the patients without nodal metastasis and that new modalities of operation and chemotherapy may be necessary for the patients with AFP producing SMGC with nodal metastasis. The necessity of chemotherapy in conventional-type SMGCs with nodal involvement remains to be studied in future.

Adenocarcinoma↗

PubMed1998

Tumor vascularity predicts recurrence in differentiated thyroid carcinoma.

BACKGROUND: New prognosticators are necessary for optimizing the extent of thyroidectomy and adjuvant radiotherapy in differentiated thyroid carcinoma. METHODS: Tumor microvessel density (MVD), expression of thymidine phosphorylase (dThdPase) and CD68 stained macrophages were evaluated in 71 differentiated thyroid carcinomas by an immunohistochemical method. RESULTS: The recurrence-free survival was significantly (P <0.05) shorter in patients with hypervascular tumors but was not related to the dThdPase expression. Significant (R = 0.323, P <0.001) correlation between dThdPase expression score and increment in MVD was documented. Frequent high MVD and dThdPase expression were encountered in tumors >3 cm. Twenty-two of the 27 (82%) patients expressing high dThdPase were also evaluated positive for CD68 (P <0.001). CONCLUSIONS: Tumor MVD might be a new prognostic indicator of differentiated thyroid carcinoma, whereas dThdpase expression with high MVD might serve to identify a subgroup of thyroid carcinoma patients as potential candidates for adjuvant radiotherapy.

Adult↗

PubMed1998

Serum carcinoembryonic antigen as a prognostic factor in resectable gastric cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor marker useful in the diagnosis and management of colorectal cancer. When CEA levels are positive in gastric cancer patients, they could be useful prognostic indicators. However, the value of CEA as a tumor marker for gastric cancer remains a matter of controversy. STUDY DESIGN: We measured preoperative serum CEA levels in 196 patients with resectable gastric cancer between May 1986 and April 1996 and then evaluated the correlation between serum CEA levels, clinicopathologic features, and prognostic information. RESULTS: Serum levels of CEA were above the normal range in 29 of 196 (14.8%) surgically resected patients (range, 5.2-570 ng/mL). Among 100 early gastric cancers confined to the submucosal layer, only 7 patients (7.0%) had positive CEA levels, but among 96 advanced cancers, 22 patients (22.9%) had high CEA levels. The CEA positive patients had more macroscopically infiltrative tumors, a more prominent serosal invasion, more frequent lymph nodes involvement, and a more advanced stage than did the CEA negative patients. The 3- and 5-year cumulative disease-specific survival rates of patients positive for serum CEA were 39.6% and 31.7%, respectively; these rates for patients negative for CEA were 83.0% and 77.3%, respectively (p < 0.0001 for comparison of survival curves). In various clinicopathologic parameters, nine parameters (tumor size, macroscopic type, type and time of operation, Laurén classification, depth of invasion, lymph node involvement, CEA, alpha-fetoprotein [AFP], and carbohydrate antigen [CA] 19-9) showed statistically significant differences in the cumulative survival rates. Of these nine parameters, independent prognostic factors by multivariate analysis were depth of invasion (T1, 2 versus T3, 4, p < 0.0001), serum CEA levels (negative versus positive, p = 0.0003), and lymph node metastasis (negative versus positive, p = 0.0005). CONCLUSIONS: Preoperative serum CEA levels provide a predictive value in determining tumor stage and prognostic information for patients with potentially resectable gastric cancer during the preoperative period.

Adenocarcinoma↗

PubMed1998

Effectiveness of weekly subcutaneous recombinant human erythropoietin administration for chemotherapy-induced anemia.

The effects of weekly subcutaneous recombinant human erythropoietin (r-hEPO) administration on anemia during chemotherapy including cisplatin and 5-fluorouracil in patients with head and neck carcinomas were examined. Weekly subcutaneous r-hEPO administration in cancer patients has not been investigated previously. Patients were treated with r-hEPO 100 IU/kg (2 patients), 200 IU/kg (6 patients), or 400 IU/kg (5 patients), or placebo, and effectiveness was evaluated by monitoring hemoglobin concentration changes after administration for 8 weeks. Hemoglobin concentrations in all 3 r-hEPO dosage groups were higher than that in the control group during chemotherapy. All r-hEPO doses produced improvements in the anemia induced by chemotherapy; however, the 400 IU/kg dose was most effective. The requirement for blood transfusions decreased in patients receiving r-hEPO therapy, and no significant side-effects were associated with r-hEPO administration. These results suggest that chemotherapy-induced anemia can be prevented by weekly subcutaneous r-hEPO administration.

Aged↗

PubMed1998

Tauroursodeoxycholic acid protects cholestasis in rat reperfused livers: its roles in hepatic calcium mobilization.

Tauroursodeoxycholic acid (TUDCA) is of potential benefit in cholestatic disorders. However, the effect of TUDCA on hepatic ischemia-reperfusion injury is unknown. We studied this subject with particular regard to its roles in hepatic calcium mobilization. Three doses of TUDCA were used with continuous intravenous infusion (1.0, 0.1, and 0.01 micromol/kg body weight/min). At 3 hr after 1 hr of ischemia and reperfusion in 70% rat liver, high-dose TUDCA reduced hepatic reperfused injury according to biochemical and histological findings and significantly increased bile flow after reperfusion. It significantly increased tissue calcium content and serum calcium concentration after reperfusion. Furthermore, it also enhanced biliary calcium concentration and total output during reperfusion. In conclusion, TUDCA has a salutary effect on ischemia-reperfusion injury of the liver. However, it is still unclear how the calcium mobilization induced by TUDCA is associated with the hepatoprotection against ischemia-reperfusion injury.

Animals↗

PubMed1998

Synchronous and metachronous lung carcinomas: molecular evidence for multicentricity.

The present study is aimed to evaluate the genetic evidence for multicentricity of synchronous and metachronous multiple lung carcinomas. Nineteen cases of synchronous multiple lung carcinomas and 11 cases of metachronous multiple lung carcinomas were analyzed for p53 protein overexpression by immunohistochemistry (DO-7) and for genetic abnormality of the p53 gene by loss of heterozygosity (LOH) at chromosome 17p and by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. They were also analyzed for K-ras mutation. DNA from three patients was also sequenced by the dideoxy sequencing method to confirm the presence of mutations and determine the base substitutions. Different spectrums of genetic changes, which were evaluated by a combination of p53 mutation, LOH at chromosome 17p and p53 overexpression, were observed in 11 of 19 cases of synchronous multiple lung carcinomas (57.9%) in the present study. Similarly, five of 11 cases of metachronous multiple lung carcinomas (45.4%) showed a different pattern of genetic changes. The present data suggest that some of the multiple carcinomas have different clonal origins, although their histological types are identical, and support the use of genetic markers in the differential diagnosis between metastasis and second primary carcinoma of the lung.

Adult↗

PubMed1998

Inferior vena caval thrombosis after traumatic liver injury.

We report here the case of a 35-year-old man who presented with inferior vena cava thrombosis (IVCT) after blunt hepatic trauma. The IVCT was incidentally detected by computed tomography (CT) 35 days after deep parenchymal suturing and suture approximation for liver lacerations. The patient denied any symptoms of thrombophlebitis. However, he had presented with significantly elevated values of FDP-D-dimer and a modest increase in plasminogen concentration, which indicated that he had been in a hypercoagulable and hypofibrinolytic state after the operation. He had not undergone any prophylactic anticoagulant therapy because of his concomitant subarachnoid hemorrhage and huge hepatic hematoma. The patient was treated with an emercy thrombectomy. Posttraumatic IVCT is extremely rare phenomenon. We should consider IVCT in patients with a severe hepatic injury, particularly if their coagulation system change into hypercoagulable and hypofibrinolytic state. Additionally, this case made us reflect on the treatment of traumatic liver injury.

Adult↗

PubMed1998

Identification, functional characterization, and developmental expression of two nonallelic parathyroid hormone (PTH)/PTH-related peptide receptor isoforms in Xenopus laevis (Daudin).

Complementary DNAs encoding two nonallelic PTH/PTH-related peptide (PTHrP) receptor (PPR) isoforms, xPPR-A and xPPR-B, were isolated from a kidney complementary DNA library of the tetraploid African clawed frog Xenopus laevis. Both isoforms differ in their coding region by 19 amino acids, and lack the region corresponding to the mammalian exon E2. When expressed in mammalian COS-7 cells, both receptor isoforms bound radiolabeled PTH-(1-34) and PTHrP-(1-36) analogs with comparable affinity, and both unlabeled peptides equivalently stimulated the accumulation of cAMP. xPPR-A also mediated inositol phosphate turnover in COS cells and stimulated channel-mediated current changes in voltage clamp experiments after injection into oocytes. Using ribonuclease protection analysis, significant xPPR-A messenger RNA expression was first detected in neurula stage embryos, which subsequently increased approximately 30-fold during tadpole development. Expression reached a maximum at the metamorphotic climax, when isoform B also became detectable at significant levels, and subsequently declined in postmetamorphotic froglets. In the adult frog, xPPR-A was prominently expressed in lung, brain, small bowel, and skin, whereas isoform B was highest in lung, heart, and brain. Using an xPPR-A antisense riboprobe for in situ hybridization, expression appeared during metamorphosis at all sites of chondrogenesis, specifically in the maturing zone of the amphibian growth plate. xPPR-A expression was also seen in a subpopulation of mononuclear cells, possibly representing osteoblasts that line perichondral bone and diaphyseal bone trabeculae. Our findings suggest that xPPRs serve a prominent role in amphibian skeletal development and possibly other functions during embryonal and early larval development.

Aging↗

PubMed1998

Long-term prospective study of body composition and lipid profiles during and after growth hormone (GH) treatment in children with GH deficiency: gender-specific metabolic effects.

GH has many effects on metabolism in addition to promoting growth. We studied changes in body composition and lipid profiles during and after GH treatment in 94 children with GH deficiency. Sixty-two subjects (46 boys and 16 girls) were evaluated at the beginning and during 36 months of GH treatment. The other 32 (21 boys and 11 girls) who had already been treated with GH were examined after the discontinuation of GH for a 6-month period. The height SD scores at the beginning and the discontinuation of GH treatment were -2.81 and -1.34 in boys and -3.14 and -1.38 in girls, respectively. The percent body fat (BF) significantly decreased from 16.5% to 11.7% in boys and from 16.7% to 11.6% in girls during the first 6 months of GH treatment (P < 0.01). BF subsequently remained constant in boys, but started to increase in girls from the 18th month of treatment. Lean body mass (kilograms) increased linearly throughout the treatment in both sexes (P < 0.01). Mean total cholesterol (TC) values decreased as a result of marked declines in low density lipoprotein cholesterol in both sexes, although statistical significance was detected only in boys (P < 0.01). High density lipoprotein cholesterol (HDLC) and apolipoprotein AI (Apo-AI) rapidly increased only in boys (P < 0.01). Triglyceride, Apo-AII, Apo-B, Apo-CII, Apo-CIII, Apo-E, and lipoprotein(a) showed no significant changes compared with baseline levels. Mean TC/HDLC and Apo-B/Apo-AI ratios decreased during treatment in both sexes, but the difference from baseline was significant only in boys (P < 0.01). After discontinuation of GH treatment, BF increased, and lean body mass decreased in boys (P < 0.01), whereas these variables did not change in girls. TC and low density lipoprotein cholesterol increased in boys within 6 months of discontinuing GH (P < 0.05). Other lipoproteins did not change in either sex, except for lipoprotein(a), which decreased significantly 6 months after the cessation of GH treatment in boys (P < 0.01). The mean TC/HDLC and Apo-B/Apo-AI ratios increased in boys slightly, but insignificantly. We concluded that GH treatment has beneficial effects on body composition and lipid profiles in both boys and girls with GH deficiency, although there are considerable gender differences. These beneficial effects of GH were reversed after the discontinuation of GH treatment, suggesting an important role of GH for GH-deficient children in the maintenance of normal metabolism even after the completion of linear growth.

Adolescent↗

PubMed1998

Comparative glucoregulatory responses of mice to restraint and footshock stress stimuli.

Effects of two types of stress, restraint and footshock, on plasma glucose level, insulin secretion, and glucose uptake by the liver, heart and femoral muscle were investigated in mice. Plasma glucose level gradually increased and reached maximum at 60 min after the onset of restraint stress, while footshock stress slightly increased plasma glucose level only 15 min after the onset of the stress, and this subsequently decreased significantly. The basal plasma insulin level and glucose-induced insulin secretion significantly decreased during both the stress stimuli. Glucose uptake by the femoral muscle was slightly increased during restraint stress, and was significantly increased during footshock stress. These results suggest that the transient increase in plasma glucose level during the early period of both stress stimuli might be caused by the inhibition of insulin secretion, and subsequent decrease in plasma glucose level during the latter phase of both stress stimuli was probably due to the increase in glucose uptake by the skeletal muscle. The present study confirmed that there was a difference in stress-induced glucoregulatory changes between restraint stress and footshock stress. This difference might be due to the degree of muscle movement during the stress stimuli.

Animals↗

PubMed1998

[A case of neurofibromatosis type I associated with basal meningocele and abnormal vessels].

A 21-year-old man with neurofibromatosis type 1 (NF 1) had many widespread cutaneous neurofibroma on his right face. Magnetic resonance imaging (MRI) revealed basal meningocele due to dysplasia of the skull base. Carotid and vertebral angiograms revealed occlusion of the right internal carotid artery, persistent primitive trigeminal artery. We have reviewed the clinical and radiographic features of this case of neurofibromatosis, meningocele and cerebral arterial abnormalities. NF associated with both intracranial vascular malformation and meningocele is very rare, and in our case both were thought to arise congenitally as a manifestation of mesodermal dysplasia. Careful follow up using MRI and MR angiography should be performed for such patients.

Adult↗

PubMed1998

[Measurement of coronary flow reserve using adenosine 5'-triphosphate in dogs].

Adenosine 5'-triphospate (ATP) was compared with adenosine and papaverine for the measurement of coronary flow reserve in 12 anesthetized dogs. Intracoronary bolus injection of ATP (1 ml, 1-500 microM) produced a dose dependent increase in the blood flow of the left anterior descending artery, which attained the plateau at the dose of 100 microM. The ratio of peak to resting coronary flow volume (coronary flow reserve) with 100 microM of ATP (3.5 +/- 0.5) was similar to that with 200 microM of adenosine (4.0 +/- 0.7) and 50 mM of papaverine (3.7 +/- 0.8). Hemodynamic variables did not change after administration of each drug, except left ventricular regional wall motion abnormality during papaverine injection. The coronary flow reserve as measured after intracoronary ATP administration (100 microM) decreased as the grade of stenosis of the left anterior descending artery progressed. In addition, the flow reserve was similar to that of adenosine or papaverine administration at each stenosis grade. Intravenous administration of ATP (1,000 micrograms/min) caused a similar increase in coronary blood flow as intracoronary ATP injection (100 microM). However, premedication with 8-phenyltheophylline, an adenosine receptor blocker, significantly suppressed the coronary dilatory effect of intravenous ATP and intracoronary adenosine but not the effect of intracoronary ATP. These results indicate that intracoronary ATP is useful for measuring coronary flow reserve and that its coronary dilatory effect is not mediated by metabolysis to adenosine.

Adenosine↗

PubMed1997

Usefulness of low doses of atropine to quantify the vagal stimulus-response relation in patients with congestive heart failure.

The response of low doses of atropine is reported to be attenuated in patients with congestive heart failure (CHF). Judging from the main site of action of low doses of atropine, we may be able to assess the functional state of the vagal center in the central nervous system. This study examines the clinical significance of heart rate (HR) response to a low dose of atropine in patients with CHF. Low and high doses of atropine were administered intravenously in 72 patients with CHF. HR after a low (parasympathomimetic) dose injection was assessed by the ratio Rm (minimal HR/basal HR), and after a high (parasympatholytic) dose by the ratio R1 (augmented HR/basal HR). Rm and R1 were related to indexes of CHF. Rm increased with progression of CHF (0.92 +/- 0.03 in New York Heart Association functional class I, 0.98 +/- 0.05 in class II, and 1.00 +/- 0.04 in class III). It also correlated with ejection fraction (r = -0.48, p <0.01) and more importantly, with peak oxygen uptake (r = -0.59, p <0.01). R1 exhibited weak correlation with basal HR (r = -0.33, p <0.05) and ejection fraction (r = 0.31, p <0.05), but had no correlation with other indexes. The vagal center may be already blunted in New York Heart Association class II with respect to increased Rm, which may be related to depressed exercise capacity. A low dose of atropine injection offers a simple and safe method for providing important information on the functional state of the vagal center in the central nervous system in patients with CHF.

Adult↗

PubMed1997

Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5.

Hedgehog (hh) family proteins appear to use the conserved targets in their signalling pathway including Patched (Ptc), Smoothened (Smo), and Gli. Although Indian hedgehog (Ihh) plays an important role in endochondral bone formation, the involvement of hh signalling molecules in skeletogenesis is unknown. We cloned a mouse (m) Smo cDNA and studied the expression patterns of Ihh, Ptc, Smo, and Gli mRNAs in mouse chondrogenic EC cells, ATDC5. The deduced amino acid sequence of mSmo consisted of 793 amino acids and was 98 and 93% homologous to the rat (r) Smo and human (h) Smo, respectively. In ATDC5 cells, the expression of Ihh mRNA paralleled that of type X collagen mRNA. Smo, Ptc, and Gli mRNAs were constitutively expressed throughout chondrogenesis and the subsequent cartilage differentiation processes except for the transient decrease in Ptc mRNA at the cellular condensation stage. Our data suggest that hh signalling molecules may be involved in chondrogenesis and cartilage differentiation in ATDC5 cells.

Amino Acid Sequence↗

PubMed1997

Enzyme immunoassay to detect antituberculous glycolipid antigen (anti-TBGL antigen) antibodies in serum for diagnosis of tuberculosis.

We report the development of an EIA specific for antituberculosis antibody in human serum for the clinical evaluation of tuberculosis. We developed a TLC immunostaining method to detect specific antigens for antibodies in the serum of patients with tuberculosis. The detected specific antigens, TDM and specific gylcolipid fraction, were individually purified from M. tuberculosis H37Rv by column chromatography. The two purified fractions were mixed and the mixture, termed TBGL antigen, was applied to an enzyme immunoassay suitable for the measurement of antituberculosis antibodies in serum. This EIA meets all the requirements of routine clinical assay in terms of sensitivity (detection limit: 0.125 U/ml), reproducibility (total CV : 3.3-6.0%), accuracy (recovery: 96-105%), simplicity and rapidity (< 2.5 h). Clinical validation of the assay was confirmed by the measurement of the anti-tuberculosis antibody in the serum of normal subjects and patients with pulmonary tuberculosis. The EIA tested in this study showed a high serodiagnostic discriminating power (90% sensitivity and 98% specificity).

Adult↗