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Biomedical subjects

H Koga

Publications and source records attributed to H Koga.

At least 55 records · Page 3Linked to original sources
PubMed2000

Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas.

A homozygous mutation at bp 677 in the gene for the methylenetetrahydrofolate reductase (MTHFR) was previously shown to be associated with a decreased risk of colorectal cancer. We examined the relation between the MTHFR genetic polymorphism and risk of colorectal adenoma in Japanese men using 205 cases of colorectal adenomas and 220 controls of normal total colonoscopy. The homozygous mutation was not measurably associated with colorectal adenomas. The findings corroborate the lack of an association between the MTHFR genotype and colorectal adenomas, but do not deny the possibility that the genotype may be involved in the late stage of colorectal carcinogenesis.

Adenoma↗
PubMed2000

Phosphoglycerate kinase deficiency: an adult myopathic form with a novel mutation.

The authors report a 36-year-old man with exertional myoglobinuria and muscle cramp without hemolytic anemia or CNS symptoms. They found a deficiency of phosphoglycerate kinase (PGK) activity in muscle and erythrocytes and a 4-base pair deletion in exon 6 of the PGK gene. This mutation may cause a frameshift, yielding an abnormal stop codon in exon 6 by which a truncated PGK protein was produced. This phenotype is caused by a novel mutation of the PGK gene.

Adult↗
PubMed2000

Molecular analysis of mechanisms regulating drug sensitivity and the development of new chemotherapy strategies for genitourinary carcinomas.

The emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

Drug Resistance, Multiple↗
PubMed2000

High prevalence of anticardiolipin antibodies in hepatitis C virus infection: lack of effects on thrombocytopenia and thrombotic complications.

Hepatitis C virus (HCV) causes various extrahepatic immunologic abnormalities. Recently, an association between HCV infection and antiphospholipid syndrome, including thrombocytopenia, has been reported. However, the precise relationship between thrombocytopenia and anticardiolipin antibodies in patients with chronic HCV infection is not fully understood; likewise, the association of antiphospholipid syndrome and various liver diseases is not well understood. To evaluate the prevalence and importance of antiphospholipid antibodies in various chronic liver diseases, we determined the levels of anticardiolipin antibodies, platelet numbers, and levels of platelet-associated immunoglobulin G (PA-IgG) and thrombin-antithrombin III complex (TAT) in patients with chronic HCV infection, chronic hepatitis B virus (HBV) infection, and primary biliary cirrhosis (PBC). The prevalence of anticardiolipin antibodies in patients with HCV infection was significantly higher than that in control subjects or individuals with the other liver diseases examined. However, there was no significant correlation between anticardiolipin antibodies and platelet counts or TAT. The frequency of thrombotic complications was similar in anticardiolipin antibody-positive and -negative patients with chronic HCV infection. Further, sera from all but one anticardiolipin antibody-positive HCV patient were negative for phospholipid-dependent anti-beta2 glycoprotein I antibodies. Our results suggest that anticardiolipin antibodies are frequently found in patients with chronic HCV infection, but they do not appear to be of clinical importance. Immunologic disturbances induced by HCV or prolonged tissue damage in systemic organs as a result of the extrahepatic manifestations of HCV infection may induce the production of antibodies to various cardiolipin-binding proteins or phospholipids.

Antibodies, Anticardiolipin↗
PubMed2000

Recent progress in the study of pathogenesis of ossification of the posterior longitudinal ligament.

The pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unknown. Gene analysis and molecular biology have been introduced in recent years, and etiologic and pathological clarifications are being achieved. An important role of the genetic background in the development of this disease was demonstrated by pedigree survey, twin survey, and HLA haplotype study. The results of gene linkage study showed that patients with OPLL have a significantly higher incidence of genetic abnormalities found in the XI collagen (alpha)2 gene (COL11A2) region. From the gene mapping of this abnormality, the abnormal N-propeptide of the COL11A2 gene was found to be responsible. We are planning to undertake genetic analysis of the whole of chromosome VI to find the pathogenic genes responsible for OPLL in addition to COL11A2. A cell biological approach is also necessary to make clear the relationship between abnormalities of the COL11A2 gene and ossification of the ligament. In future, identification of the susceptible gene, elucidation of its function, and study toward the development of preventive and therapeutic drugs will advance.

Chromosome Mapping↗
PubMed2000

Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes.

BACKGROUND & AIMS: Wilson's disease is a genetic disorder characterized by the accumulation of copper in the body caused by a defect of biliary copper excretion. The Wilson's disease gene has been cloned; however, the precise localization of the gene product (ATP7B) and its role in biliary copper excretion have not been clarified. METHODS: We constructed a chimeric protein between green fluorescent protein (GFP) and ATP7B (GFP-ATP7B) and expressed it in a human hepatoma cell line (Huh7) and isolated rat hepatocytes. The Golgi apparatus, late endosomes, lysosomes, and bile canaliculus were visualized by fluorescence microscopy. Brefeldin A and nocodazole were used to redistribute the Golgi proteins. Bafilomycin A1 was used to analyze the association between GFP-ATP7B and the late endosomes. RESULTS: GFP-ATP7B colocalized with rhodamine-dextran and late endosome markers but not with the Golgi markers, lysosome markers, or a tight junction protein. Brefeldin A and nocodazole redistributed the Golgi proteins, but they did not affect the distribution of ATP7B. CONCLUSIONS: Although it is widely believed that ATP7B is located at the Golgi apparatus, its main localization is in late endosomes. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.

Adaptor Protein Complex gamma Subunits↗
PubMed2000

6-Substituted 2,2-bis(fluoromethyl)-benzopyran-4-carboxamide K+ channel openers.

In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-pentafluoroethyl-2H-1-ben zopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol.

Animals↗
PubMed2000

Design of the Y1-receptor-selective cyclic peptide based on the C-terminal sequence of neuropeptide Y.

We designed four cyclic peptides which are mimics of the C-terminal region of human neuropeptide Y (NPY) on the basis of the structural model of NPY. One of these cyclic peptides, c[D-Cys29-L-Cys34]NPY Ac-29-36 (YM-42454), exhibited significantly higher affinity for the Y1-receptor than the corresponding C-terminal linear fragment, NPY Ac-28-36. Interestingly, YM-42454 showed binding affinity for the Y1-receptor in spite of the lack of the N-terminal sequence of NPY, whereas it did not show any binding affinity for the Y2-receptor. This conformationally restricted Y1-selective peptide would provide some insights into the bioactive conformation of the C-terminal region of NPY.

Animals↗
PubMed2000

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.

BACKGROUND: To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS: Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS: Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS: The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.

Adult↗
PubMed2000

Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis.

Cholestasis is frequently associated with inflammatory bowel disease. Because some cholestasis is resulted from altered hepatocyte tight junctions (TJs) or the canalicular multispecific organic anion transporter, we have investigated the following topics in a rat model of inflammatory bowel disease: (1) alterations in hepatocyte TJs and in the canalicular multispecific organic anion transporter, (2) etiologic factors for cholestasis, and (3) effects of antibiotics on cholestasis. Rats with trinitrobenzene sulfonic acid-induced colitis were studied 24 hours after treatment. Hepatocyte TJs and the canalicular multispecific organic anion transporter were evaluated by immunostaining for TJ-associated proteins, 7H6 and ZO-1, and multidrug resistance protein 2 (mrp2). To investigate etiologic factors causing cholestasis, portal endotoxin and proinflammatory cytokines were examined. The effects of polymyxin B, penicillin G, or metronidazole on immunostaining for 7H6, ZO-1, mrp2, and cholestasis were investigated. (1) Immunostaining for 7H6 and ZO-1 colocalized outlining the bile canaliculi and immunostaining for mrp2 localized on the canalicular membrane in controls. Treatment with trinitrobenzene sulfonic acid induced significant cholestasis and caused translocation of immunostaining for 7H6, but not that for ZO-1, to the cytoplasm and diminished immunostaining for mrp2 on the canaliculus membrane. (2) The levels of portal endotoxin, but not proinflammatory cytokines, was increased. (3) Polymyxin B, but not the other antibiotics, prevented alterations in immunostaining for both 7H6 and mrp2, and cholestasis. We described that both hepatocyte TJs and the canalicular multispecific organic anion transporter were altered and that gut-derived endotoxin levels in the portal blood were increased in this rat colitis model.

Animals↗
PubMed2000

Laparoscopic adrenalectomy for pheochromocytoma: comparison with open adrenalectomy and comparison of laparoscopic surgery for pheochromocytoma versus other adrenal tumors.

OBJECTIVE: To compare the efficacy of laparoscopic adrenalectomy for pheochromocytoma with that of conventional open adrenalectomy for pheochromocytoma and laparoscopic surgery for other adrenal tumors. PATIENTS AND METHODS: Fifty-four patients with adrenal tumors, including 10 cases of pheochromocytoma, 18 cases of Cushing's syndrome, 20 cases of primary aldosteronism, and 6 cases of nonfunctioning tumors, were evaluated. A historical group of 7 consecutive patients who underwent conventional open adrenalectomy for pheochromocytoma was also studied. RESULTS: Laparoscopic adrenalectomy for pheochromocytoma was successful in 9 of the 10 patients. There was no difference in tumor size, operation time, estimated blood loss, or occurrence of hypertensive episodes during surgery between patients treated with laparoscopic procedures and those treated with open surgery. However, the number of days to first postoperative oral feeding and first ambulation, length of hospitalization, and number of patients requiring parenteral analgesics were significantly smaller after laparoscopic surgery than after open surgery. There was no significant difference in operation time, estimated blood loss, incidence of intraoperative complications, or postoperative recovery between patients who underwent laparoscopic adrenalectomy for pheochromocytoma and those who underwent laparoscopic surgery for other adrenal lesions. CONCLUSIONS: Laparoscopic adrenalectomy does not increase the specific risks associated with surgery for pheochromocytoma. It is a minimally invasive alternative to conventional open adrenalectomy.

Adolescent↗
PubMed2000

Structure-affinity relationships of C-terminal cyclic analogue of neuropeptide Y for the Y1-receptor.

We previously reported that a cyclic octapeptide amide, c[D-Cys29, Cys-34]NPY Ac-29-36 (YM-42454) showed a high affinity for Y1-receptors in SK-N-MC cells (Ki=0.047,microM) but not for Y2-receptors in the porcine hippocampus membranes (Ki>10microM). To explore the critical residues of this unique cyclic peptide for Y1-binding activity, the structure-affinity relationships were investigated by means of amino acid replacement. The results indicated that the hydrophobic side-chains of Leu30 and Ile31, the guanidinium groups of Arg33 and Arg33, and the C-terminal amide are critical for the binding affinity of YM-42454 to the Y1-receptor. On the other hand, Thr32 in YM-42454 might not be critical for the Y1-binding affinity. 1H-NMR studies for YM-42454 and its derivatives have suggested that the critical residues are involved in the direct interaction with a Y1-receptor rather than in maintaining the bioactive conformation.

Animals↗
PubMed2000

Superficial temporal artery dilatation in a patient with infectious temporal headache clinically mimicking temporal arteritis.

A 57-year-old woman noticed a pulsatile shooting headache in her right temporal region 3 days after extraction of a tooth from the right mandible. The following day, a localized headache over the right superficial temporal artery (STA), low grade fever, and jaw claudication appeared and progressed subacutely. Seven days after the onset, magnetic resonance imaging and angiography (MRI/MRA) disclosed inflammatory swelling of the right temporal muscle and dilatation of the right STA. All the symptoms disappeared following antibiotic treatment, and neuroimaging findings were improved. In conclusion, MRA is thought to be useful to non-invasively identify reversible inflammatory dilatation of extracranial vessels.

Bacterial Infections↗
PubMed2000

Effect of Er:YAG laser irradiation on acid resistance to bovine dentin in vitro.

Resin bond strength to Er:YAG laser irradiated dentin has been reported to be lower than that of unlased dentin. The reasons have been much discussed, but not clarified. One hypothetical cause has been discussed that lased dentin is acid resistant, therefore, the etching effect of acid conditions decreases. The purpose of this study was to evaluate the acid resistance of laser-irradiated dentin and compare it with the dissolved mineral of Er:YAG laser irradiated dentin and unlased dentin. This experiment was a pilot study to assess the etching effect of pre-conditioner for resin bonding to lased dentin. Bovine dentin was irradiated by Er:YAG laser and immersed in 0.1 M lactic buffer solution (pH 4.0). The dissolved Ca and P in the solution were then both measured. Dissolved Ca from lased dentin was not significantly different from that coming from unlased dentin (p > 0.05). The molar ratio of Ca/P did not differ significantly between lased and unlased dentin, either (p > 0.05). Under FE-SEM view before immersion, the dentin surface was covered with a smear layer in unlased dentin, but this layer was not clearly observed in lased dentin. These results suggested that the lased dentin had little or no resistance to lactic buffer solution.

Acid Etching, Dental↗
PubMed2000

Accumulation of intracellular platinum is correlated with intrinsic cisplatin resistance in human bladder cancer cell lines.

We investigated the mechanism of intrinsic resistance to cisplatin in human transitional cell cancer (TCC) using 7 human bladder cancer cell lines, which were derived from untreated TCC of the urinary bladder. The sensitivity to cisplatin was different from cell line to cell line, and a 15-fold difference was observed between the most sensitive line and the most resistant line. No significant correlation was observed between the content of intracellular glutathione and the resistance to cisplatin. In contrast, a positive correlation was seen between intracellular cisplatin accumulation and cisplatin resistance. The expression of drug resistance-related genes including glutathione S-transferase pi, gamma-glutamyl-cysteine synthetase, multidrug resistance-1, multidrug resistance-associated protein, DNA topoisomerase I, topoisomerase II, human canalicular multispecific organic anion transporter, and thioredoxin was not significantly related to cisplatin resistance. These data suggest that intracellular cisplatin may contribute to intrinsic cisplatin resistance and may therefore be a useful biomarker to predict cisplatin sensitivity in human untreated TCC.

Carcinoma, Transitional Cell↗
PubMed2000

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction.

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.

Acute Kidney Injury↗
PubMed2000

Hand assisted laparoscopic radical nephrectomy for renal carcinoma using a new abdominal wall sealing device.

PURPOSE: We report our initial experience with a hand assisted laparoscopic radical nephrectomy for patients with renal carcinoma, and compare our results to those of conventional open radical nephrectomy. MATERIALS AND METHODS: The clinical data on 6 consecutive patients who underwent hand assisted laparoscopic radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal wall sealing device. We compared the results of this procedure with those of conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell carcinoma. RESULTS: The hand assisted laparoscopic radical nephrectomy for renal carcinoma was successfully performed without any major or minor complications in all 6 patients. Mean operation time for the laparoscopic group was significantly longer than that for the open surgery group (303 minutes versus 224 minutes, p = 0.0042). However, no significant difference was observed in mean estimated blood loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the open surgery group). The frequency of parenteral analgesia postoperatively in the laparoscopic group was significantly lower than that in the open surgery group (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to recover more rapidly than the open surgery group. The abdominal wall sealing device was easy to attach to the abdominal wall, and allowed rapid hand removal and reinsertion. CONCLUSIONS: Our preliminary results indicate that a hand assisted laparoscopic radical nephrectomy with the abdominal wall sealing device is an effective and safe surgical procedure, and is less invasive than open radical nephrectomy.

Adult↗