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Biomedical subjects

H Konno

Publications and source records attributed to H Konno.

At least 37 records · Page 2Linked to original sources
PubMed2001

Impact of repeat hepatectomy on recurrent colorectal liver metastases.

BACKGROUND: Hepatic recurrence is seen in approximately 40% of patients undergoing hepatectomy for colorectal metastases. This study was designed to assess the risks and clinical benefits of repeat hepatectomy for those patients. METHODS: Twenty-six patients underwent repeat hepatectomy for hepatic recurrence, and their clinical data were retrospectively reviewed for operative morbidity and mortality, performance level, and survival. RESULTS: There was no operative mortality after repeat hepatectomy. Operative bleeding was significantly increased in the second hepatectomy; but operating time, duration of hospital stay, and performance status after the second hepatectomy were comparable with those of the initial hepatectomy. The median survival time from the second hepatectomy was 31 months, and the 3- and 5-year survival rates were 62% and 32%, respectively. A short disease-free interval (6 months or less) between the initial hepatectomy and diagnosis of hepatic recurrence in the remnant liver was significantly associated with poor survival after the second hepatectomy. CONCLUSIONS: Repeat resection contributed to clinical benefits for selected patients with hepatic recurrence after the initial hepatectomy for colorectal liver metastases. However, appearance of hepatic recurrence within 6 months or less after the initial hepatectomy is a poor prognostic factor for repeat hepatectomy.

Adult↗
PubMed2001

Computer-based methods for the mouse full-length cDNA encyclopedia: real-time sequence clustering for construction of a nonredundant cDNA library.

We developed computer-based methods for constructing a nonredundant mouse full-length cDNA library. Our cDNA library construction process comprises assessment of library quality, sequencing the 3' ends of inserts and clustering, and completing a re-array to generate a nonredundant library from a redundant one. After the cDNA libraries are generated, we sequence the 5' ends of the inserts to check the quality of the library; then we determine the sequencing priority of each library. Selected libraries undergo large-scale sequencing of the 3' ends of the inserts and clustering of the tag sequences. After clustering, the nonredundant library is constructed from the original libraries, which have redundant clones. All libraries, plates, clones, sequences, and clusters are uniquely identified, and all information is saved in the database according to this identifier. At press time, our system has been in place for the past two years; we have clustered 939,725 3' end sequences into 127,385 groups from 227 cDNA libraries/sublibraries (see http://genome.gse.riken.go.jp/).

5' Untranslated Regions↗
PubMed2001

Prevention of hepatic and peritoneal metastases by the angiogenesis inhibitor fr-118487 after removal of growing tumor in mice.

We established a mouse rising dbl quote, left (low)primary tumor resection model" in which a transplanted tumor was resected after an orthotopic transplantation of colorectal cancer tissue to estimate the therapeutic effect of an angiogenesis inhibitor on metastasis. The angiogenesis inhibitor FR-118487 is a member of the fumagillin family. Here, 1 mg / kg / day of FR-118487 was subcutaneously administered to nude mice for 1 week, 2 weeks, or 4 weeks through an osmotic pump. Liver metastasis developed in 7 of 9 control mice, 2 of 6 mice that underwent the tumor resection 2 weeks after transplantation (early resection), and in all 7 of the mice that underwent the tumor resection 4 weeks after transplantation (late resection). In the short treatment trial, the FR-118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal metastases, whereas its administration after the late resection had no effect on liver metastasis. In the prolonged treatment trial, inhibitory effects of prolonged treatment with FR-118487 on both hepatic and peritoneal metastases after the late resection were clearly demonstrated. The mice of the resection-alone group all died within 106 days after tumor inoculation, due to metastases of colon carcinoma. In contrast, half of the mice that underwent resection and then received antiangiogenic therapy were alive at the end of the observation period (160 days after transplantation). In conclusion, the combination of surgery and subsequent antiangiogenic therapy may be useful to prevent the distant metastasis of colorectal cancer and to improve the prognosis of patients with colorectal cancer.

Angiogenesis Inhibitors↗
PubMed2001

Urokinase receptor and vascular endothelial growth factor are synergistically associated with the liver metastasis of colorectal cancer.

Considering recent findings that the urokinase plasminogen activation (PA) system is involved in invasion and vascular endothelial growth factor (VEGF) is involved in angiogenesis of colorectal cancer, we evaluated these factors in the liver metastasis of primary colorectal cancer. Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2), and were also assayed immunohistochemically for expression of VEGF protein. Among the PA system factors, both the levels of uPAR and PAI-1 were significantly higher in larger tumors than in smaller ones, and were also significantly higher in tumors that invaded subserosa, serosa or adjacent organs than in mucosal, submucosal tumors or in tumors that invaded the muscle layer. The uPAR levels were significantly higher in tumors with liver metastasis than in those without. VEGF overexpression was significantly more frequent in tumors with lymph node involvement or liver metastasis than in those without. Among the PA system factors, the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis. The combination of high uPAR level and overexpression of VEGF was associated with the worst prognosis in patients with colorectal cancer. These results suggest that uPAR and VEGF might contribute synergistically to the liver metastasis of colorectal cancer.

Colorectal Neoplasms↗
PubMed2001

Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.

Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.

Animals↗
PubMed2001

Cloning full-length, cap-trapper-selected cDNAs by using the single-strand linker ligation method.

We have developed the single-strand linker ligation method (SSLLM), which uses DNA ligase to add a dsDNA linker to single-stranded (ss) full-length cDNA. The linkers have random 6-bp (dN6 or dGN5) 3' overhangs that can ligate to any cDNA sequence, thereby facilitating the production of cDNA libraries with titers exceeding 1 x 10(6) independent clones. We confirmed that the 5' ends of cDNA inserts cloned by using SSLLM are full-length and include the 5' untranslated regions. The great advantage of our method is that the elimination of the GC tail simplifies the sequencing and protein translation of the full-length clones. Further, our method tags ss cDNAs more efficiently than does the traditional RNA ligase reaction.

5' Untranslated Regions↗
PubMed2001

Brain single-photon emission CT studies using 99mTc-HMPAO and 99mTc-ECD early after recanalization by local intraarterial thrombolysis in patients with acute embolic middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: The brain distribution of 9mTc-hexamethylpropyleneamine oxime (HMPAO) correlates with regional brain perfusion, whereas 99mTc-ethyl cysteinate dimer (ECD) reflects not only perfusion but also the metabolic status of brain tissue. We compared 99mTc-ECD single-photon emission CT (SPECT) with 99mTc-HMPAO SPECT early after recanalization by local intraarterial thrombolysis (LIT) in patients with acute embolic middle cerebral artery occlusion. We also assessed the predictive value of 99mTc-HMPAO and 99mTc-ECD SPECT for the development of ischemic brain damage. METHODS: 99mTc-HMPAO and consecutive 99mTc-ECD SPECT studies were performed in 15 patients within 3 hours of LIT. The two SPECT studies were obtained independently using a subtraction technique. SPECT evaluation was performed using semiquantitative region-of-interest analysis. Noninfarction, infarction, and hemorrhage were identified by follow-up CT or MR imaging. RESULTS: Forty-five lesions were identified (21 noninfarctions, 19 infarctions, and five hemorrhages). Regardless of 99mTc-HMPAO SPECT findings, lesions showing isoactivity (count rate densities of 0.9 to 1.1 as compared with the contralateral side) on 99mTc-ECD SPECT were salvaged. Lesions with hypoactivity (values < 0.9) on 99mTc-ECD SPECT developed irreversible brain damage. Hemorrhage appeared in lesions with both hyperactivity (values > 1.1) on 99mTc-HMPAO SPECT and hypoactivity on 99mTc-ECD SPECT. CONCLUSION: The brain distribution of 99mTc-ECD in a reperfused area identified by 99mTc-HMPAO SPECT early after recanalization of acute ischemic stroke is dependent on cerebral tissue viability. By combining 99mTc-ECD and 99mTc-HMPAO SPECT, performed within the first few hours of LIT, it is possible to identify patients at risk for hemorrhagic transformation reliably.

Aged↗
PubMed2001

[Effective combination chemotherapy for a recurrent case of carcinoma of the remnant stomach].

A 69-year-old-man underwent distal gastrectomy for gastric carcinoma in 1988. Another gastric carcinoma was discovered in the remnant stomach in March 1995. Total gastrectomy and lymph node dissection were performed. CEA was up and we detected a big left suprarenal mass by abdominal CT. Suprarenalectomy was performed in June 1997. The swelling of lymph nodes was detected by CT and CEA was up to 1,000. Combination chemotherapy with intermittent 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) was performed. CEA suddenly decreased and lymph node swelling was reduced.

Adenocarcinoma↗
PubMed2001

Dynamic and static 99mTc-ECD SPECT imaging of subacute cerebral infarction: comparison with 133Xe SPECT.

UNLABELLED: 99mTc-ethylcysteinate dimer (99mTc-ECD) SPECT imaging reportedly fails to show reflow hyperemia in patients with subacute stroke. This study attempts to determine the clinical usefulness of dynamic 99mTc-ECD SPECT in evaluating regional blood flow in subacute cerebral infarction and the kinetic behavior of 99mTc-ECD in infarct areas. METHODS: 133Xe and consecutive dynamic and static 99mTc-ECD SPECT studies were performed on 24 patients with cortical infarction in the middle cerebral artery territory 13-15 d after the onset of a stroke. Image contrast between infarct and contralateral control areas on 99mTc-ECD tomograms (ECD uptake ratio) was compared with that on cerebral blood flow (CBF) images obtained using 133Xe inhalation (CBF ratio). RESULTS: In all cases, ECD uptake ratios from static images were lower than CBF ratios. This tendency was obvious when CBF in the infarct area increased above the normal control value, and no significant correlation was found between ECD uptake ratios from static images and CBF ratios. Only in the infarct areas with CBF below the normal control value, however, was a significant correlation between the two maintained (r = 0.795; P = 0.0011). A very strong correlation was found between CBF ratios and ECD uptake ratios on both the first dynamic scan (36 s after injection) (r = 0.991; P < 0.0001) and the second dynamic scan (72 s after injection) (r = 0.945; P < 0.0001). The correlation coefficient decreased in a time-dependent manner, with no significant correlation observed after the fourth dynamic scan (144 s after injection). On the other hand, significant correlations were observed on all dynamic scans only in the infarct areas with CBF below the control value. CONCLUSION: Super-early images of dynamic 99mTc-ECD SPECT provide a close imaging contrast with CBF and reveal reflow hyperemia in areas with irreversible changes produced by subacute stroke, which static 99mTc-ECD SPECT images fail to show. Decreased retention of the tracer in the infarct areas with hyperperfusion causes an underestimation of CBF on static 99mTc-ECD SPECT images. Given these results, we believe that dynamic 99mTc-ECD SPECT is an effective clinical tool to evaluate regional blood flow in subacute cerebral infarction.

Adult↗
PubMed2001

[A case of mediastinal esophago-bronchogenic cyst associated with high serum level of CA 19-9].

We report a case of mediastinal esophago-bronchogenic cyst in a patient with a high serum level of CA 19-9. A 49-year-old man presented with a complaint of dysphagia. Chest X-ray, CT, and MRI showed posterior mediastinal cystic shadow which was diagnosed preoperatively. The serum level of CA 19-9 was 158 U/ml. We underwent extirpation of the cyst through video-assisted thoracoscopic surgery (VATS) and confirmed to be a bronchogenic cyst histologically. The serum level of CA 19-9 returned to normal after the operation.

Bronchogenic Cyst↗
PubMed2001

[Neuropathology of longstanding subacute myelo-optico-neuropathy (SMON): an autopsy case of SMON with duration of 28 years].

The present case, 78-years-old female, had been troubled with SMON during 28 years, and was suddenly died from cerebral hemorrhage. The neuropathology characteristic for SMON could not be revealed in the spinal cord on routine histological preparations. There were decreasing number of immunopositive granules in the nucleus gracilis of medulla oblongata for synaptophysin, and in the marginal zone of the lumbar dorsal horn for substance P. These findings showed the presence of tractus gracilis degeneration and the disappearance of nociceptive fibers from the dorsal roots, respectively. To elucidate the histopathological changes of the spinal cord in long standing cases with SMON, the 11 cases reported were reviewed. The mean duration from the onset to death was 22.8 years(16 to 33 years). The mean age was 76.3 years old(54 to 92), and the 10 cases were female. All cases showed sensory impairment of the lower extremities, while deep tendon reflex exaggerated was seen in 7 cases. There were nine cases involving dorsal funiculi degeneration of the spinal cord, in contrast the lateral funiculi alternation were noticed in only two cases. It was considered that the corticospinal tract alteration becomes undiscernible during the long course, although the dorsal funiculi degeneration remained.

Aged↗
PubMed2001

[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction].

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.

Friedreich Ataxia↗
PubMed2000

Inverse regulation of F1-ATPase activity by a mutation at the regulatory region on the gamma subunit of chloroplast ATP synthase.

Chloroplast ATP synthase is a thiol-modulated enzyme whose DeltamuH(+)-linked activation is strongly influenced by reduction and the formation of a disulphide bridge between Cys(199) and Cys(205) on the gamma subunit. In solubilized chloroplast coupling factor 1 (CF(1)), reduction of the disulphide bond elicits the latent ATP-hydrolysing activity. To assess the regulatory importance of the amino acid residues around these cysteine residues, we focused on the three negatively charged residues Glu(210)-Asp-Glu(212) close to the two cysteine residues and also on the following region from Leu(213) to Ile(230), and investigated the modulation of ATPase activity by chloroplast thioredoxins. The mutant gamma subunits were reconstituted with the alpha and beta subunits from F(1) of the thermophilic bacterium Bacillus PS3; the active ATPase complexes obtained were purified by gel-filtration chromatography. The complex formed with a mutant gamma subunit in which Glu(210) to Glu(212) had been deleted was inactivated rather than activated by reduction of the disulphide bridge by reduced thioredoxin, indicating inverse regulation. This complex was insensitive to the inhibitory CF(1)-epsilon subunit when the mutant gamma subunit was oxidized. In contrast, the deletion of Glu(212) to Ile(230) converted the complex from a modulated state into a highly active state.

Adenosine Triphosphate↗
PubMed2000

The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion.

BACKGROUND: This study was designed to verify the involvement of platelet-activating factor (PAF) in renal damage associated with hepatic ischemia and reperfusion (HIR) injury through the release of endothelin (ET)-1 and to determine the modulating effect of a specific PAF receptor antagonist on these insults in rats. METHODS: Male rats pretreated with either normal saline as a vehicle (NS group) or intravenous TCV-309, a PAF receptor antagonist (TCV group), were subjected to 120 min of total hepatic ischemia under an extracorporeal portosystemic shunt. Plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight were determined under nonischemic conditions and at 1, 3, and 6 hr of reperfusion after hepatic ischemia. Changes in mean arterial blood pressure and renal tissue blood flow measurements in the kidney were determined throughout the experiment. RESULTS: Increased plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight after HIR in the NS group were significantly suppressed by TCV-309 pretreatment. Mean arterial blood pressure and renal tissue blood flow after HIR in the TCV group were significantly improved when compared with those in the NS group. These effects resulted in attenuation of structural hepatic and renal damage with the improvement of 7-day survival (62%). CONCLUSIONS: The present study demonstrates that renal damage as well as critical liver injury is produced after reperfusion following 120 min of total hepatic ischemia. A PAF receptor antagonist may be therapeutically useful to protect against these types of damage via indirect modulation of plasma ET-1 levels.

Animals↗
PubMed2000

Methylation and downregulated expression of mac25/insulin-like growth factor binding protein-7 is associated with liver tumorigenesis in SV40T/t antigen transgenic mice, screened by restriction landmark genomic scanning for methylation (RLGS-M).

Restriction landmark genomic scanning for methylation (RLGS-M) was used to detect alterations in DNA methylation associated with murine SV40 T/t antigen-induced hepatocarcinogenesis. An altered locus/spot (S130) was cloned and found to correspond to sequences in the 5' flanking region and 5' portion of the cDNA for the murine mac25/insulin-like growth factor binding protein-7 (Igfbp-7) gene. IGFBPs are believed to be capable of binding insulin, Igf1, and Igf2 and modulating mitogenic effects. Previous studies have shown that Igf2 has an important role in promoting liver tumorigenesis. Quantitative PCR was used to access the methylation status of the NotI site just 5' to the coding region and the expression level of the mac25/igfbp-7 gene. The results indicated that the degree of methylation was inversely related to the expression level and is consistent with a role for DNA methylation in silencing mac25/Igfbp-7 gene expression and function for mac25/Igfbp-7 as a tumor suppressor gene.

Animals↗