Biomedical subjects

H Konno

Publications and source records attributed to H Konno.

At least 91 records · Page 5Linked to original sources

PubMed1998

Primary dissection of the hepatic artery: report of a case.

Dissecting aneurysms of the hepatic artery are extremely rare. We report herein the case of a 51-year-old man with massive hepatic metastases from rectal carcinoma, who was found incidentally to have a left hepatic artery aneurysm by a preoperative angiography. After replacing the left hepatic artery with a 2-cm segment of long saphenous vein, an extended right lobectomy with partial resection of the left lateral segment for multiple metastases was successfully performed. To prevent thrombus formation at the anastomosis, the Pringle maneuver was not used during dissection of the hepatic parenchyma. Histological examination of the resected specimen showed a dissecting aneurysm of the left hepatic artery, but there were no findings to suggest the etiology of this disease. The patient is currently alive 13 months after his operation without any evidence of further recurrence of the carcinoma. To the best our knowledge, 12 case reports of this anomaly have been documented, but only one of these describes a successful operation. The clinical features and etiology of the hepatic artery aneurysm that develops independent of other vascular diseases are discussed following this case report.

Aortic Dissection↗

PubMed1998

Surgical management for a malignancy of the digestive organs accompanied with an abdominal aortic aneurysm.

Surgical management of patients with simultaneous coexisting malignancy of the digestive organs and an abdominal aortic aneurysm (AAA) remains controversial. In the five patients who underwent the aneurysmectomy first, no complications developed after an aneurysmectomy and a resection of malignancy could be performed within 4 weeks, whereas postoperative complications after the resection of malignancy developed in two of them. Two patients underwent a one-stage operation, in which one was unable to tolerate the two procedures, and no postoperative complications were seen; however, one patient with cardiac dysfunction who first underwent an aneurysmectomy died 3 months after operation due to cardiac and renal failure. These results indicate that the aneurysmectomy first is preferred, when such patients do not have absolute indications of malignancy or AAA; however, a one-stage operation should be chosen when the patients show a disturbance of key organs.

Adult↗

PubMed1998

Prodigiosins uncouple mitochondrial and bacterial F-ATPases: evidence for their H+/Cl- symport activity.

Prodigiosin, metacycloprodigiosin, and prodigiosin 25-C all inhibited the acidification activity of submitochondrial and bacterial (Escherichia coli) F-ATPases (FoF1-ATPases) strongly (IC50 = 20-30 and 24-30 pmol/mg protein, respectively), without affecting significantly the ATP hydrolysis activity. Their effect on the acidification activity was rapid and reversible, showing non-competitive apparent Ki values of the order of nM to sub-nM. However, unlike FCCP (an ordinary uncoupler of oxidative phosphorylation), they showed no protonophoric activity, as demonstrated by the absence of acceleration of ATP hydrolysis. Prodigiosins also inhibited the acidification of proteoliposomes reconstituted from phospholipids and purified F-ATPase of E. coli, suggesting that their acidification-inhibitory effect is not due to the inhibition of anion channels. They did not, however, inhibit the ATP-dependent formation of membrane potential of F-ATPase vesicles. Furthermore, they inhibited and quickly reversed acidification by F-ATPase only in the presence of chloride, and not in the presence of gluconate anion. Finally, they induced swelling of liposomes and submitochondrial particles in isotonic solution of ammonium chloride but not ammonium gluconate, suggesting that intravesicular entry of Cl- is promoted by prodigiosins. These results suggest that prodigiosins uncouple F-ATPases through promotion of H+/Cl- symport (or OH-/Cl- exchange) across vesicular membranes.

Animals↗

PubMed1998

Antitumor effect of a neutralizing antibody to vascular endothelial growth factor on liver metastasis of endocrine neoplasm.

Distant metastasis of gastrointestinal endocrine neoplasm is resistant to currently available treatments. Because hematogenic metastasis is dominant, anti-angiogenic drugs are expected to be a novel therapy for this neoplasm. In the present study, the therapeutic effect of vascular endothelial growth factor neutralizing antibody (VEGFAb) on liver metastasis of an endocrine neoplasm was investigated experimentally. Cecal transplantation into nude mice of small pieces of EN-1, a xenotransplanted human intestinal endocrine neoplasm, resulted in liver metastasis. A treated group (n = 19) received 100 micrograms/mouse of VEGFAb intraperitoneally on alternate days from day 10 after tumor transplantation, and the control group (n = 19) received saline. Five of the 19 control mice died of tumor progression, of which 2 could not be evaluated. The cecal tumor weighed 6316 +/- 2333 mg (n = 17) in the control group and 1209 +/- 837 mg (n = 19) in the treated group (P < 0.01) 6 weeks after transplantation. Liver metastasis developed in 16 of 17 control mice and in 2 of 19 treated mice (P < 0.01). The VEGF level of the whole cecal tumor in the control group was significantly higher than that in the treated group (305.1 +/- 174.1 vs. 54.7 +/- 41.2 mg; P < 0.001). VEGFAb did not cause any body weight loss (28.52 +/- 1.63 in the control vs. 28.44 +/- 1.71 g in the treated group). These results indicate that VEGFAb may be a novel therapeutic agent for endocrine neoplasm with distant metastasis.

Aged↗

PubMed1998

Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype.

A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.

Aged↗

PubMed1998

Relationship of p53 and vascular endothelial growth factor expression of clinicopathological factors in human scirrhous gastric cancer.

Although scrirrhous cancer has the highest malignant potential among various types of gastric cancer, its pathogenesis is still unclear. The relationship between expression of p53 or vascular endothelial growth factor (VEGF) and clinicopathological variables was investigated by immunohistochemical analysis of archival specimens from 40 patients with scirrhous gastric cancer. Staining for p53 and VEGF was observed in the nuclei and cytoplasm of the tumor cells, respectively. There was no significant association between expression of p53 or VEGF and sex, age, depth of invasion, lymph node metastasis or histological stage. Peritoneal dissemination was the most frequent mode of recurrence, and the depth of tumor invasion was a crucial factor. The recurrence rate was 83.9% (2/9) in patients without serosal invasion. Only 7 out of 40 patients (17.5%) survived without recurrence. Among them, the VEGF-positive rate was 14.3% (1/7), whereas it was 52.6% (10/19) in the patients with recurrence. There was no correlation between p53 and VEGF staining. These findings suggest that the progression of scirrhous gastric cancer may be promoted by VEGF overexpression, which is not upregulated by p53 mutation.

Adenocarcinoma, Scirrhous↗

PubMed1998

Quantitative analysis of vascular endothelial growth factor in colon cancer. Clinical and experimental.

Although some studies have shown that overexpression of vascular endothelial growth factor (VEGF) mRNA or protein is correlated with the progression of human malignancies, it is still unknown whether the VEGF level in tumor tissue correlates with tumor growth or metastasis. The present clinical study enrolled 26 patients with colon cancer and revealed that the VEGF level in tumor tissue was significantly higher than in adjacent normal tissue (220.93 +/- 217.64 pg/mg protein in the tumor tissue; n = 26; 38.93 +/- 20.26 in the normal tissue; n = 26) and significantly correlated with tumor size, whereas it did not correlate with other clinicopathological variables. The animal study involved orthotopic transplantation of a human colon cancer strain into nude mice and demonstrated that the VEGF level of transplanted tumor tissue (2,318.5 +/- 1,340.9 pg/mg protein) was significantly correlated with tumor weight (1,856.4 +/- 928.9 mg), but not with the number of the liver metastatic foci. These results indicate that VEGF produced by primary tumors of colon cancers may mainly promote primary tumor growth.

Adult↗

PubMed1998

Quinolone-resistant mutations of DNA gyrase increase sensitivity to acriflavine.

DNA gyrases were constructed to possess the quinolone-resistant (D87N in GyrA or K447E in GyrB) and acrB (S759R-R760C in GyrB) mutations and their sensitivities to acriflavine and oxolinic acid were examined. Both quinolone-resistant mutations in GyrA and GyrB increased acriflavine sensitivities in the supercoiling assay irrespective of the co-presence of the acrB mutation. In the DNA binding assay, however, the hypersensitvity caused by the GyrB (K447E) mutation was observed only in the co-presence of the acrB mutation; the presence of the acrB mutation, which not affecting acriflavine sensitivity, reduces the extent of DNA binding, as reported previously. Thus, the quinolone-resistant mutation site in GyrB is likely to be involved in DNA binding which is not detectable in acrB+ gyrase. Furthermore, oxolinic acid was found to enhance DNA binding of the gyrase having GyrB (acrB-K447E), supporting a recent proposal that quinolone binding to the DNA-gyrase complex does not require DNA breakage.

4-Quinolones↗

PubMed1998

[Treatment of hepatocellular carcinoma: application of vascular surgery].

The present status of hepatic resection for hepatocellular carcinoma (HCC) is reviewed with special reference to the vascular aspects. Hepatic resection combined with portal tumor thrombectomy has been attempted in Japan. This procedure may be effective in the prevention of rupture of esophageal varices and making transcatheter arterial embolization possible. According to the report of Yamaoka and his associates, the 1- and 3-year survival rates of 29 patients treated with this combined procedure were 53% and 12%, respectively. This surgical strategy may thus yield survival benefits. In patients with a tumor near the confluence of the major hepatic vein and inferior vena cava, resection of segments 4b, 7, and 8 combined with hepatic vein reconstruction has been performed, which allows functional preservation of the residual liver. The historical development of hepatic vascular exclusion (HVE) is also reviewed. HVE can be performed safely using a centrifugal active pump, even in patients with cirrhosis. Hepatic resection combined with removal of tumor thrombus in the right atrium has been carried out using extracorporeal circulation. There are reports that at least two patients undergoing this operation survived more than 2 years after surgery. The hepatic warm ischemic time should be less than 60 min. Vascular surgery techniques are being increasingly applied in Japan for the treatment of HCC. Such surgery can be performed safely even in patients with cirrhosis. Improvement of long-term survival in patients undergoing such procedures remains an unresolved problem, however.

Carcinoma, Hepatocellular↗

PubMed1998

[Therapeutic effect of angiogenesis inhibitors on liver metastases of human colorectal carcinoma].

Angiogenesis is essential for the growth of solid tumors. Antiangiogenic therapy has therefore attracted considerable interest as a novel therapy for various tumors including colorectal carcinoma. We experimentally investigated the therapeutic effect of TNP-470, a nonspecific inhibitor of angiogenic factors, and vascular endothelial growth factor (VEGF)-neutralizing antibody (VEGFAb), was a VEGF-specific inhibitor, on liver metastases of colon carcinoma using a murine orthotopic transplantation model. TK-4 and TK-13 are moderately differentiated adenocarcinoma strains established in our department which express VEGF mRNA and protein. Administration of TNP-470 30 mg/kg significantly inhibited the liver metastases of both strains, as did administration of VEGFAb 100 micrograms/mouse. The therapeutic effect on liver metastases was more dominant with antiangiogenic therapy than with chemotherapy (mitomycin C). Furthermore, the sustained effect of TNP-470 induced tumor dormancy and consequently improved the survival of the animals. These results suggest that antiangiogenic treatment will be a potent therapy for liver metastases of human colorectal carcinoma in the future.

Animals↗

PubMed1998

[Abdominal aneurysm].

Ulcer bleeding in the upper gastrointestinal tract is one of severe complications in the patients with abdominal aortic aneurysm (AAA). Retrospective analysis of patients with AAA and prospective endoscopic study revealed ulcer lesions occurred more frequently in AAA patients than in controls. Decreased gastric mucosal blood flow (GMBF) and accompanied consumption coagulopathy (CC) mainly contribute to the development of postoperative ulcer bleeding. Recently, the number of AAA patients with ulcer bleeding has been decreased remarkably after we started the anti-ulcer therapy for AAA patients with low GMBF or/and the administration of heparin for the patients with CC.

Aortic Aneurysm, Abdominal↗

PubMed1997

Alteration of reticuloendothelial phagocytic function and tumor necrosis factor-alpha production after total hepatic ischemia.

BACKGROUND: This study was conducted to determine whether the duration of total hepatic ischemia influences reticuloendothelial phagocytic activity and tumor necrosis factor (TNF)-alpha production after reperfusion. METHODS: Male rats pretreated with either normal saline (NS group) or gadolinium chloride (7 mg/kg) for 2 days to inhibit Kupffer cell function (GC group) were subjected to 30, 60, or 90 min of total hepatic ischemia. RESULTS: The animals tolerated hepatic ischemia well for 30 and 60 min. Although the 7-day survival rate of the NS group decreased to 28% after 90 min of hepatic ischemia, that of the GC group improved significantly to 68% (P<0.01). In the NS group, plasma alanine transaminase and TNF-alpha levels after reperfusion increased with the length of hepatic ischemia. The phagocytic index (PI) after 60 min of reperfusion following 90 min of hepatic ischemia showed significant depression compared with the preischemic level and the value after 30 or 60 min of ischemia. The GC group had significantly lower plasma alanine transaminase and TNF-alpha levels as well as significantly less polymorphonuclear leukocyte infiltration in the liver compared with the NS group. The preischemic PI was significantly inhibited in the GC group when compared with that in the NS group, but PI in the GC group did not change significantly after reperfusion, irrespective of the ischemic time. CONCLUSIONS: This study demonstrated that warm ischemia of up to 60 min is tolerable for normal rat liver without a detrimental effect on phagocytic activity. Modulation of Kupffer cell function may have the potential to prevent reperfusion injury after hepatic ischemia, which may allow safe prolongation of the ischemic time.

Alanine Transaminase↗

PubMed1997

Restriction landmark genomic scanning (RLGS-M)-based genome-wide scanning of mouse liver tumors for alterations in DNA methylation status.

Restriction landmark genomic scanning for methylation (RLGS-M) was used to detect, and subsequently clone, genomic regions with alterations in DNA methylation associated with tumorigenesis. Use of a methylation-sensitive enzyme for the landmark cleavage allows analysis of changes in methylation patterns. In this study, we used RLGS-M to analyze SV40 T antigen-induced mouse liver tumors derived from interspecific F1 hybrids between Mus spretus (S) and C57BL/6 (B6). Because 575 S- and B6-specific RLGS loci/spots have been mapped, tumor-related alterations in the RLGS profile could be immediately localized to specific chromosomal regions. We previously found that the loss of contiguous loci/spots could be attributed primarily to DNA loss, whereas loss of solitary loci/spots could be attributed primarily to DNA methylation. In this study, we examined 30 mouse liver tumor samples for loss of the 507 mapped loci/spots. Fourteen solitary loci/spots found to be absent or reduced in more than 75% of tumor samples were cloned and subjected to DNA sequence analyses. Two loci were identified as alpha4 integrin and p16/CDKN2, genes reported to be involved in tumorigenesis. Thus, RLGS-M can detect alterations in the methylation status of known tumor suppressor genes and provide a method for detecting and subsequently cloning novel genomic regions that undergo alterations in methylation during tumorigenesis.

Animals↗

PubMed1997

Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice.

The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer.

Adenocarcinoma↗

PubMed1997

acrB mutation located at carboxyl-terminal region of gyrase B subunit reduces DNA binding of DNA gyrase.

Mutations that exhibit susceptibility to acriflavine have been isolated and classified as acr mutations in Escherichia coli. We cloned the acrB gene, which has been identified as a mutation of the gyrB gene, and found a double point mutation altering two consecutive amino acids (S759R/R760C) in the COOH-terminal region of the gyrase B subunit. The mutant B subunit was found to associate with the A subunit to make the quaternary structure, and the reconstituted gyrase showed an 80-fold reduction of specific activity in DNA supercoiling assay; the sensitivity to acriflavine was not different in the same unit of wild-type and mutant gyrases. The mutant enzyme retained intrinsic ATPase activity, but DNA-dependent stimulation was observed infrequently. A gel shift assay showed that acriflavine inhibited the DNA binding of gyrase. The acrB mutation also reduced significantly the DNA binding of gyrase but did not change the sensitivity to acriflavine. These results revealed that the acrB mutation is related to the inhibitory mechanism of acriflavine; and the acriflavine sensitivity of the mutant, at least in vitro, is caused mainly by reduction of the enzyme activity. Further, our findings suggest that the COOH-terminal region of the B subunit is essential for the initial binding of gyrase to the substrate DNA.

Amino Acid Sequence↗

PubMed1997

Immunohistochemical studies on endothelial cell phenotype in hepatocellular carcinoma.

To examine the phenotype of the sinusoidal endothelial cells (SECs) surrounding tumor cells and the process of capillarization in hepatocellular carcinoma (HCC), 51 primary HCCs, 4 adrenal metastases, and 3 portal tumor thrombi were immunohistochemically stained with monoclonal antibodies (MAbs) for CD4, CD14 (lipopolysaccharide-binding protein complex receptors), and CD32 (Fc gamma receptor II), which are specifically found on the SECs in normal liver, but not on ordinary vascular endothelial cells (ECs). Immunostaining was also performed for CD36 (thrombospondin receptors), EN4 antigen (Ag) (a pan-vascular endothelial cell Ag), PAL-E Ag (a venous and capillary EC Ag), factor VIII-related Ag (FVIIIRAg), and laminin. MAb 25F9, which identifies macrophages, was simultaneously used with the other MAbs to distinguish macrophages from SECs in HCCs (HCC SECs). CD4, CD14, and/or CD32 were found on HCC SECs only in 12 well-differentiated primary HCCs showing a thin trabecular or pseudoglandular tumor cell arrangement. These 12 tumors were smaller than those without CD4-, CD14-, and/or CD32-positive SECs (P < .05). Among them, 7, 5, and 11 tumors were negative or only partially positive for laminin, PAL-E Ag, and FVIIIRAg, respectively. Staining for laminin and PAL-E Ag showed an inverse relationship to the expression of CD4, CD14, and CD32 on HCC SECs and the tumor differentiation. In conclusion, the phenotypes of the SECs in early and well-differentiated HCC are thought to be similar to those of the SECs in normal liver. With progressing tumor dedifferentiation the HCC SECs lose the phenotypes peculiar to liver SECs and acquire the characteristics of capillary ECs, though both types of phenotypical change occur independently of each other.

Antigens, CD↗

PubMed1997

Direct hepatic vein anastomosis during hepatectomy for colorectal liver metastases.

BACKGROUND: When the right and middle hepatic veins (RHV and MHV) and all the short hepatic veins are removed during resection of segments (S) 7 and 8 and part of S 5 and 6 including the caudate lobe, the remainder of S 5 and 6 shows congestion, so restoration of liver function may be delayed. METHODS: In 5 patients with hepatic metastases of colorectal carcinoma, which were in the region circumscribed by the RHV, MHV, and inferior vena cava, direct hepatic vein anastomosis was performed during hepatectomy. RESULTS: Hepatic vein reconstruction took 17 to 30 minutes to complete. All 5 patients had an uneventful postoperative course, and the anastomosis was patent at 1 month after operation. One patient died of recurrent carcinoma 6 months after operation. Four have remained alive and disease free for 12, 24, 40, and 61 months. CONCLUSION: Direct hepatic vein anastomosis is an option, which should be adopted in hepatectomy, especially in patients with carcinoma invading the major hepatic veins and short hepatic veins.

Aged↗

PubMed1997

Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis.

Spinal cords of sporadic cases with amyotrophic lateral sclerosis (ALS) and normal controls were immunohistochemically examined using antibodies for nitrotyrosine (NT), Cu/Zn superoxide dismutase (SOD), and nitric oxide synthase (NOS) of brain, endothelial, and inducible forms. Immunoreactivity for NT was densely detected in the motor neurons of ALS while it was not or was only minimally detected in those of controls. The staining was also found in the axons of motor neurons of ALS, but was not found in the controls. In contrast, although immunoreactivity for Cu/Zn SOD of the motor neurons was dense in the motor neurons, it was not different between the ALS and controls. Immunoreactivities for bNOS and eNOS in the motor neurons of ALS were stronger than those of controls, and were also found in degenerated axons in the anterior horn of ALS. However, the immunoreactivity for inducible NOS was only minimally detected in the motor neurons of ALS and controls, and was not detected in the degenerated axons of ALS. These results suggest that nitration of protein-tyrosine residue is upregulated in motor neurons of the spinal cord of ALS with selective increases of brain NOS- and endothelial NOS-like immunoreactivities.

Amyotrophic Lateral Sclerosis↗