Biomedical subjects

H Konno

Publications and source records attributed to H Konno.

At least 73 records · Page 4Linked to original sources

PubMed1999

Larger and more invasive colorectal carcinoma contains larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlates well with tumor size.

BACKGROUND: Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase-type plasminogen activator (uPA) activity-independent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated. METHODS: In 100 colorectal carcinoma patients, antigen levels of u-PA, uPAR, and PAI-1 and PAI-2 were assayed in both tumor tissues and their normal counterparts. Plasma levels of soluble uPAR also were determined. RESULTS: All uPAR, uPA, PAI-1, and PAI-2 antigen levels in tumor tissue were significantly higher than those in normal tissue. Levels of both uPAR and PAI-1 were significantly higher (3.09 +/- 1.37 and 6.63 +/- 7.49, respectively) in large tumors (>/=50 mm in greatest dimension) than those in smaller tumors (< 50 mm) (2.50 +/- 1.07 and 2.72 +/- 2.70, respectively) (P < 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI-1/uPAR (r = 0.490; P < 0.0001) and PAI-1/uPA (r = 0. 469; P < 0.0001). In addition to liver metastases (P = 0.004) and lymph node involvement (P = 0.04), high levels of uPAR (P = 0.05) also were found to be of independent prognostic value by multivariate analysis. CONCLUSIONS: Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI-1 over uPAR or uPAR-bound uPA appeared to play an important role in tumor progression.

Adult↗

PubMed1999

Recurrent Miller Fisher syndrome: clinical and laboratory features and HLA antigens.

In rare cases, Miller Fisher syndrome (MFS) has been known to recur. However, clinical features of recurrent MFS have not been well analyzed, and the precipitating factors relating to recurrence remain unknown. From 1981 to 1996, we examined four patients with recurrent MFS among 28 Japanese MFS patients. In the four patients, the recurrent episodes occurred after long asymptomatic intervals, ranging from 2.5 to 12.5 years. The clinical and laboratory features of recurrent episodes were similar either to those of the initial episodes or to those of the 24 non-recurrent patients. Of the two patients tested for serum IgG anti-GQ1b antibody, both were positive. Serological HLA typing showed that all recurrent patients were both HLA-Cw3 and -DR2 positive. However, out of 13 non-recurrent patients examined, six had HLA-Cw3, and four had HLA-DR2. The frequency of HLA-DR2 among the recurrent patients was significantly higher than among healthy controls (corrected P = 0.038), and was also higher than among the non-recurrent patients but not significantly. These findings suggest that recurrent MFS is clinically the same as typical MFS and that HLA-DR2 is possibly associated with recurrence.

Adult↗

PubMed1999

Contribution of endothelin-1 to microcirculatory impairment in total hepatic ischemia and reperfusion injury.

BACKGROUND: Endothelin (ET)-1 may have a role in hepatic polymorphonuclear leukocyte infiltration as well as microcirculatory disturbance during hepatic ischemia-reperfusion (HIR) injury. This study was conducted to investigate the influence of ET-1 on the hepatic microcirculation after total HIR and to evaluate the effect of a nonselective ET receptor antagonist under these conditions. METHODS: Male rats pretreated with either normal saline (NS group) or TAK-044, a nonselective ET receptor antagonist (TAK group), were subjected to 120 min of total hepatic ischemia with extracorporeal portosystemic shunting. RESULTS: Plasma ET-1 levels increased significantly from 1 to 6 hr after reperfusion in the NS group when compared with the nonischemic control. In the early phase of reperfusion, the NS group showed significantly narrower sinusoids, lower hepatic tissue blood flow, a lower hepatic tissue oxy-hemoglobin concentration, and more hepatic neutrophil infiltration than the TAK group (P<0.05). Pretreatment with TAK-044 improved hepatic microcirculatory derangement, and resulted in significantly better 7-day survival (61.5%) with more bile production after reperfusion when compared with the NS group (P<0.01). CONCLUSIONS: The present study demonstrated that ET-1 is involved in the development of HIR injury by causing deterioration of the hepatic microcirculation. A nonselective ET receptor antagonist successfully ameliorated HIR injury through improvement of hepatic oxygenation and of the microcirculation along with reduced hepatic neutrophil infiltration.

Alanine Transaminase↗

PubMed1999

Pathophysiological role of endothelins in pulmonary microcirculatory disorders due to intestinal ischemia and reperfusion.

BACKGROUND: This study was conducted to investigate pulmonary microcirculatory disorders caused by intestinal ischemia reperfusion (IIR), and the pathophysiological roles of endothelin (ET) in acute lung injury (ALI). METHODS: Male rats were pretreated with normal saline or a nonselective ET receptor antagonist (TAK-044) and subjected to IIR (60 min of intestinal ischemia and 180 min of reperfusion). The right upper lobe of the lung was examined by intravital confocal microscopy. RESULTS: The size of arterioles and venules was not significantly reduced during IIR, but the functional capillary density (FCD) decreased significantly. TAK-044 improved the pulmonary microhemodynamics, inhibiting the accumulation of leukocytes, the pulmonary edema, and the decrease of FCD. CONCLUSIONS: In the early stage of IIR, pulmonary microhemodynamics seemed more likely to be disturbed by the decrease of FCD, than by arteriolar or venular vasoconstriction. ETs decrease the FCD, promoting the interaction between leukocytes and pulmonary vessels.

Animals↗

PubMed1999

Double cancer of the gallbladder and common bile duct associated with an anomalous pancreaticobiliary ductal junction without a choledochal cyst: report of a case.

We report herein the case of a 37-year-old woman found to have double cancer of the gallbladder and common bile duct associated with an anomalous pancreaticobiliary ductal junction (APBDJ) without a choledochal cyst (CC). Abdominal ultrasonography showed an isoechoic mass in the gallbladder, and percutaneous transhepatic biliary drainage tubography revealed incomplete obstruction in the upper portion of the common bile duct and APBDJ. The patient underwent cholecystectomy, partial hepatic resection, pancreatoduodenectomy, and portal vein reconstruction. Pathological examination of the tumors from the gallbladder and bile duct revealed papillary carcinoma and poorly differentiated adenocarcinoma, respectively, and direct continuity was not observed between the tumors. A review of the literature on six cases of multiple primary carcinoma of the biliary tract associated with APBDJ without CC is presented following this case report. Double cancer of the biliary tract was found synchronously in five patients and metachronously in one. Gallbladder cancer showed subserosal invasion in four patients, while bile duct cancer invaded the pancreas in one patient and reached the serosa in two patients. Considering the potential for cancer to arise in the biliary tract and the difficulties associated with monitoring it, cholecystectomy and resection of the extrahepatic common bile duct may be the most appropriate treatment for patients with an APBDJ without a CC.

Adenocarcinoma↗

PubMed1999

Antitumor effect of the angiogenesis inhibitor TNP-470 on human digestive organ malignancy.

The antitumor and antimetastatic effects of TNP-470, an angiogenesis inhibitor, on human gastrointestinal tumors xenotransplanted into nude mice were investigated. When two gastric cancer (MT-2 and MT-5) and two colon cancer (TK-4 and TK-13) xenografts are transplanted orthotopically into nude mice, liver metastasis develops 6 weeks after transplantation. TNP-470 30 mg/kg had a significant inhibitory effect on primary tumor growth of gastric cancers when given on alternate days from 7 days after transplantation. However, when given from 10 days or 14 days after transplantation, no inhibitory effect on the growth of any tumor xenograft was observed. In contrast, liver metastasis of each xenograft type was inhibited significantly by TNP-470. The effect of TNP-470 on prognosis was investigated using a hepatic metastatic model of rat hepatoma. Although all untreated rats that received AH-130 cell implants died within one month of massive hepatic metastasis, >50% of rats treated with TNP-470 survived for 4 months. The number of apoptotic cells in hepatic metastatic foci was significantly increased by TNP-470 administration. These results suggest that TNP-470 may provide a new approach to the treatment of digestive organ malignancies.

Animals↗

PubMed1999

Antiangiogenic therapy for liver metastasis of gastrointestinal malignancies.

In about half of the patients with gastrointestinal carcinomas, surgical excision of the primary tumor is not curative because metastasis has already occurred. Recent investigations of metastasis have shown that angiogenesis plays an important role in this process. In solid tumors angiogenesis occurs continuously to provide a blood supply for the proliferating cancer cells. As a new and potent method to control metastasis, antiangiogenic therapy has attracted considerable interest. This therapy inhibits angiogenesis, inducing a dormant state in which tumors cannot grow; the prognosis may thus be remarkably improved. Antiangiogenic agents show a characteristic antitumor effect which is different from that of chemotherapy. Based on our experimental in-vivo data, we conclude that antiangiogenic agents should not be used only for achieving tumor shrinkage, like chemotherapy. These agents should be used to control micrometastases, as the therapeutic effect on such metastasis is excellent. In addition, antiangiogenic agents may be valuable for long-term administration to maintain tumor dormancy, because drug resistance does not develop and these agents have a sustained effect. Combinations with conventional anti-cancer treatments such as chemotherapy, radiotherapy, immunotherapy, or surgery may also be valuable.

Animals↗

PubMed1999

Resection of hepatic metastases of colorectal carcinoma: 20 years' experience.

We analyzed the results and the prognostic factors influencing survival in 79 patients with metastases of colorectal carcinoma who underwent hepatectomy at our hospital in the 20-year period 1978-1998. The 5- and 10-year survival rates were 49% and 33%, respectively. Repeat hepatectomy was done 29 times in 24 patients with relapse of liver tumors. The 3- and 5-year survival rates after repeat hepatectomy were 58% and 14%, respectively. The distribution of and number of tumors in the liver, the disease-free interval from initial to second hepatectomy, and the presence of extrahepatic disease were significantly associated with survival (P < 0.01). Seven of 43 patients who underwent hilar node dissection had metastasis and 2 of them survived for more than 5 years. Repeat hepatectomy and hilar lymphadenectomy may be effective in prolonging the survival of selected patients with hepatic metastasis. We also discuss prognostic factors after extensive surgery for hepatic metastases of colorectal carcinoma.

Adenocarcinoma↗

PubMed1999

Chromosomal diagnosis in each individual blastomere of 5- to 10-cell bovine embryos derived from in vitro fertilization.

Chromosomal normality and sex were diagnosed in each blastomere of bovine embryos derived from in vitro fertilization (IVF). Bovine embryos developing to the 5- to 10-cell stage were separated into individual blastomeres with 0.5% protease. After treatment with 100 ng/mL vinblastine sulfate for 8 to 10 h, they were prepared for chromosome samples. In total, 33 bovine embryos and 185 blastomeres were examined. Chromosomal normality was analyzed in 43.8% (81/185) of the blastomeres and 60.6% (20/33) of the embryos; while chromosomal anomalies were found in 16 (80%, 16/20) of the embryos, 5 haploid embryos and 11 mosaic (n/2n) embryos. Mosaicism characteristic of the opposite sex in X-and Y-chromosomes was found in 2 haploid embryos, and that of a Y-chromosome and of XX chromosomes in 1 n/2n embryo. Various sex-chromosome compositions were also observed in the other 10 chromosomal mosaic n/2n embryos.

Animals↗

PubMed1999

Therapeutic effect of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) on liver metastasis of xenotransplanted human colon carcinoma.

S-1 [1 M tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypyridine (CDHP)-1 M potassium oxonate (Oxo)], was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CDHP and Oxo. The therapeutic effect of S-1 on human colon cancer xenografts (TK-13) with high metastatic potential to the liver was evaluated. Small pieces of TK-13 were sutured into the cecal wall of 52 nude mice, and the animals were randomly divided into 3 groups [control (n=17), UFT (combination of 1 M FT and 4 M uracil) (n=18) and S-1 (n=17)]. S-1 or UFT was administered orally at an equitoxic dose (S-1, 7.5 mg/kg; UFT, 17.5 mg/kg as FT) for 37 consecutive days beginning 10 days after the transplantation. S-1 showed higher tumor growth inhibition than UFT (P<0.05) and also showed a significant anti-metastatic effect on liver metastasis, while UFT did not. Liver metastasis developed in only 2 of the 17 mice (12%) in the S-1 group, whereas it developed in 9 of the 17 (53%) and 7 of the 18 (39%) in the control and UFT group, respectively. Analysis of AUC (area under the curve) revealed that S-1 yielded higher 5-FU levels in both tumor tissue (1.6 times) and plasma (2.5 times) than UFT. These results suggest that S-1 will show a higher clinical therapeutic effect against human colorectal cancer than UFT.

Animals↗

PubMed1999

Antitumor effect on human gastric cancer and induction of apoptosis by vascular endothelial growth factor neutralizing antibody.

Induction of apoptosis by antiangiogenic therapy has been suggested as a new anticancer strategy. To clarify the mechanism of the antitumor effect achieved by inhibition of vascular endothelial growth factor (VEGF), which is a major mediator of angiogenesis, we used an orthotopic transplantation model of human gastric carcinoma line (MT2) treated with a monoclonal VEGF neutralizing antibody (VEGF Ab). We histologically examined the microvessel density (MVD) and the apoptotic index (AI) in this model. Transplanted tumor growth was significantly inhibited by the VEGF Ab (P = 0.03), and there was a significant decrease in the number of mice with liver metastasis (P = 0.004). The MVD detected by immunohistochemical staining with ER-MP12 antibody was 33.6 +/- 8.0 in the control group and 21.1 +/- 5.4 in the treated group, and the difference was significant (P < 0.0001). The AI values of the control and treated groups were 4.73 +/- 1.11 and 7.26 +/- 1.62, respectively, and this difference is also significant (P < 0.0001). However, the expression of VEGF mRNA in transplanted tumors did not show a significant difference between the control and treated groups. These results suggest that the antitumor effect of the VEGF Ab on human gastric carcinoma is exerted by inducing mild hypoxia followed by apoptosis, which does not influence VEGF mRNA expression in the carcinoma.

Adenocarcinoma↗

PubMed1999

[Steroid-responsive diffuse cerebral white matter lesions in a case of intractable fungal meningoencephalitis].

We report a case of fungal meningoencephalitis with steroid-responsive diffuse cerebral white matter lesions. A 49-year-old male developed auditory hallucination, confusion and fever, on April, 1994. He was diagnosed as having cryptococcal meningoencephalitis based on the detection of cryptococcal antigens in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole resulted in improvement of his neurologic symptoms and CSF findings. For the next seven months, he was treated with oral fluconazole and the neurological status was stable. However, soon after the dose of fluconazole was tapered, he became confused and febrile, which made him admitted to our hospital. Neurological examination on admission showed disturbance of consciousness, disorientation and meningeal irritation. The CSF examination revealed mild pleocytosis (mostly lymphocytes), elevated protein and normal glucose levels, although fungus was not detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed spotty enhanced lesions in the periventricular white matters. The neurologic symptoms were once relieved after intravenous administration of fluconazole was started, but two months later, he became comatose and needed ventilatory support, despite amphotericine B therapy. Then, a needle brain biopsy targeting the white matter lesion was done. Histopathology of the specimen showed chronic inflammation with granuloma formation and T lymphycyte infiltrate around the small vessels, though fungus was not detected in the tissue. Combined therapy with corticosteroid and antifungal agents remarkably improved the neurological symptoms as well as the MRI findings. In the present case, fungal infection possibly induced an altered immune reactions which resulted in the steroid responsive diffuse cerebral white matter lesions.

Anti-Inflammatory Agents↗

PubMed1999

[Role of cytokines in hepatic ischemia and reperfusion injury].

The liver is an organ with abundant blood flow, consisting of hepatic arterial and portal blood flow. The viability of liver tissue depends on the condition of the hepatic microcirculation which is controlled by hepatic sinusoidal lining cells. Hepatic ischemia and reperfusion (HIR) injury is inevitable in surgical procedures for liver trauma and hepatectomy as well as liver transplantation. Reperfusion through an ischemically damaged organ enhances the tissue injury. Cytokines are pivotal factors in neutrophil-mediated liver injury following HIR, while various other mediators are involved in this insult. Advances in molecular biology have allowed the identification of various cytokines. Inflammatory cytokines such as TNF-alpha are associated with the induction of cellular adhesion molecules and hepatic microcirculatory impairment based on neutrophil-vascular endothelial cell interaction. Members of the chemokine family such as IL-8, CINC, MIP-2, and MCP-1 are involved in neutrophil infiltration in the liver and remote organs. Since each cytokine has a wide variety of actions and interacts' among others' via the cytokine network, their actions in HIR injury have not been determined completely. Kupffer cells have been focused on as a source of cytokine production in HIR injury. Further studies on the mechanisms of cytokine production after HIR and analysis of regulation in the cytokine network would clarify the pathophysiology of HIR injury and the most suitable therapeutic strategy for this insult.

Cytokines↗

PubMed1999

[An autopsy case of motoneuron disease with dementia of long duration].

An autopsy case of MND with dementia, 67 years old, man, was reported. The behavioral disturbance appeared at 61 years old, and was followed by the upper limb weakness and respiratory failure. He had remained on a respirator for 56 months. The total duration of the disease was 74 months, which was far longer than mean duration of the cases previously reported, 25-30 months. The pathological findings were about essentially identical to those mentioned before, such as cortical alterations in temporal and frontal lobes, neuronal loss with gliosis in amygdaloid body and substantia nigra, and loss of lower motoneurons in anterior horn of spinal cord and in the several motor cranial nerve nuclei. There were several Bunina bodies in the remnant lower motoneurons, but no changes in the pyramidal tracts or loss of Betz cells in the precentral gyrus. Intracytoplasmic ubiquitin-immunopositive inclusions in the granule cells of hippocampal dentate gyrus were also encountered, but the number of which did not increased, compared to the preceding data. There may be frequently little correlation between the disease duration and the number of such inclusions. The regional alteration in the intermediate zone between subiculum and entorhinal cortex was revealed also at the level of the splenium of corpus callosum. It has been reported that such parahippocampal lesion may initiate at the anterior part of temporal lobe and become undiscernible at more posterior level than the lateral geniculate body. The formation of such parahippocampal lesion may be concerning with the length of disease duration. In addition, there were numerous senile plaques, diffuse or neuritic type only in the parietal lobe cortex without any other changes.

Aged↗

PubMed1998

Anti-tumor and anti-metastatic effects of human-vascular-endothelial-growth-factor-neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice.

In order to determine whether the inhibition of vascular-endothelial-growth-factor (VEGF) activity by administration of an immunoneutralizing antibody could suppress tumor growth and metastasis in spontaneous metastatic models of human colon and gastric carcinoma, 4 human carcinoma xenografts, 2 human colon carcinomas (TK4 and TK 13) and 2 gastric carcinomas (MT2 and MT5) were transplanted orthotopically into nude mice. The anti-VEGF antibody (MV833, 100 microg/mouse) or the same volume of saline was administered i.p. on alternative days from day 10 after transplantation. With each of the 4 xenografts, administration of MV833 significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied. The inhibitory effect of MV833 on primary tumor growth appeared to have no correlation with the level of VEGF in tumor. Body-weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers, and that VEGF may be a possible target for cancer therapy.

Adenocarcinoma↗

PubMed1998

Prodigiosins as a new group of H+/Cl- symporters that uncouple proton translocators.

We reported previously (Kataoka, T., Muroi, M., Ohkuma, S., Waritani, T., Magae, J., Takatsuki, A., Kondo, S., Yamasaki, M., and Nagai, K. (1995) FEBS Lett. 359, 53-59) that prodigiosin 25-C uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification, and affected glycoprotein processing. In the present study we show that prodigiosins (prodigiosin, metacycloprodigiosin, and prodigiosin 25-C) inhibit the acidification activity of H+-ATPase chloride dependently, but not membrane potential formation or ATP hydrolysis activity, and suggest that they promote H+/Cl- symport (or OH-/Cl- exchange, in its equivalence) across vesicular membranes. In fact, prodigiosins displayed H+/Cl- symport activity on liposomal membranes. First of all, they decreased the internal pH of liposomes depending on the external chloride, and raised it depending on the internal chloride when external buffer was free from chloride. Second, their effect was electroneutral and not seriously affected by the application of an inside positive membrane potential generated by K+ and valinomycin. Finally, they promoted the uptake of [36Cl] from external buffers with concomitant intraliposomal acidification when external pH was acidic relative to liposome interior. As prodigiosins hardly inhibit the catalytic activity (ATP hydrolysis) unlike well known OH-/Cl- exchangers (for example, tributyltin chloride), they should provide powerful tools for the study of molecular machinery and cellular activities involving transport of protons and/or chloride.

Animals↗

PubMed1998

Characterization of gene expression in mouse blastocyst using single-pass sequencing of 3995 clones.

To study the gene expression profile in the mouse blastocyst and to identify embryonic stage-specific genes, we randomly selected cDNAs derived from mouse blastocysts and sequenced a total of 3995 clones from one or both ends. Excluding the uninformative clones, 3395 clones were grouped as 937 different kinds of genes. Among these, 465 and 406 species showed similarity to known genes and expressed sequence tags (ESTs), respectively, whereas 66 species showed no significant similarity to any genes in known databases. Analysis of these cDNAs revealed that this library contained a variety of functional genes as well as genes that have not been detected in the human EST database; it should provide us with a useful resource for molecular analysis of developmental mechanisms. Although the human EST project is considered to represent roughly half of all genes, our findings indicate that many early stage developmental genes remain to be identified.

Animals↗

PubMed1998

Pathophysiological appraisal of a rat model of total hepatic ischemia with an extracorporeal portosystemic shunt.

BACKGROUND: Animal models of total hepatic ischemia (THI) and reperfusion injury are restricted by concomitant splanchnic congestion. This study was performed to determine the requirement suitable for an extracorporeal portosystemic shunt (PSS) to maintain the intestinal integrity in a rat model of THI. MATERIALS AND METHODS: Using a polyethylene tube (0.86 or 1 mm i.d.), PSS was placed between the mesenteric and jugular veins. Comparison was done between THI models with or without PSS and a partial ischemia model with hepatectomy of the nonischemic lobes. Well-tolerated hepatic ischemic period, portal pressure after 10 min of hepatic ischemia, portal endotoxin levels at 1 h after reperfusion, histological features of the small bowel just before reperfusion, and local jejunal and ileal blood hemoglobin oxygen saturation index (ISO2) were compared among the models. RESULTS: Animals without PSS poorly tolerated 30 min of THI. Animals receiving THI with PSS or partial hepatic ischemia tolerated a longer ischemic period (60 min) with a significantly higher small bowel ISO2, lower portal pressure and endotoxin levels (P < 0.01), and less histological damage of the small bowel when compared to those receiving THI without PSS. Portal endotoxin levels after THI with PSS using a 1-mm i.d. tube as well as partial hepatic ischemia were significantly lower than those after THI with PSS using a 0.86-mm i.d. tube. CONCLUSIONS: THI with PSS using a 1-mm i.d. tube was strikingly similar to partial hepatic ischemia in the pathophysiological profile during hepatic ischemia. PSS with a tube 1 mm or more in inner diameter offers pathophysiological advantages in experiments on THI and reperfusion.

Animals↗