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Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 289 records · Page 16Linked to original sources
PubMed1997

[Studies on bacillary dysentery cases of overseas travellers--during 1979 to 1995].

A total of 36,780,440 overseas travellers during 1979-1995 (17 years) were quarantined at Osaka and Kansai Airport Quarantine Station, 84,777 travellers reported themselves suffer from diarrhoea. Stools from 29,587 persons were bacteriologically examined. Various enteropathogenic bacteria were isolated from 9,766 (33.0%) patients of the stools examined. Isolated species were as follows: Plesiomonas shigelloides (3,234 cases); Salmonella spp. (2,236 cases); enterotoxgenic Escherichia coli (1,621 cases); Vibrio parahaemolyticus (1,959 cases); and Shigella spp. (1,242 cases). 1,278 different Shigella strains were isolated from 1,242 cases who were thus diagnosed as bacillary dysentery patients. The suspected regions or countries for infection of these cases were analysed. The serovars and antibiotic-sensitivities of the isolated strains were examined. Colicine typing of S. sonnei strains were also done. The results can be summarized as follows. 1) The most cases (53.4%) were infected in India. 2) The percentage distribution of sub-species of the strains was as follows; S. sonnei (57.8%), S flexneri (29.8%), S. boydii (8.4%), and S. dysenteriae (4.0%), respectively. 3) The major colicine type of S. sonnei strains were type 6 and 0. 4) The percentage of Antibiotic-resistant strains of each sub-species was S. dysenteriae (92.2%), S. sonnei (89.4%), S. flexneri (87.1%), and S. boydii (84.9%), respectively. The percentage of Antibiotic-resistant strains of S. flexneri were increased annually.

Adolescent↗
PubMed1997

[Vertical oculomotor disorders in progressive supranuclear palsy and spino-cerebellar degeneration].

We performed neuro-otological investigation of vertical oculomotor disorders in 35 patients with degenerative disease [progressive supranuclear palsy (PSP) and spino-cerebellar degeneration], and obtained the following results: 1) In the patients with PSP, in addition to vertical oculogyric disorder both saccade and pursuit eye movements were disturbed, and the disturbance of saccade movement was greater. Even the patients without an oculogyric disorder were all found to have decreased saccade velocity, suggesting that this disorder may occur earliest in PSP. 2) In olivo-ponto-cerebellar atrophy (OPCA), saccade movement was less disturbed than that in PSP. In contrast, pursuit movement was disturbed more frequently. 3) In late cortical cerebellar atrophy (LCCA), vertical ocular movement was hardly disturbed compared with OPCA. 4) Concerning dentate nuclear degeneration, we cannot reach a conclusion because of the few cases studied, but a variety of oculomotor disorders were seen; both saccade and pursuit movements were disturbed, but saccade movement was less disturbed than in PSP. 5) In visual suppression tests, enhancement in the light area was frequently seen in the patients with PSP and OPCA, but none with LCCA showed such change. In addition, enhancement of the light area under visual suppression was significantly correlated with vertical oculomotor disorder.

Adult↗
PubMed1997

Diagnosis of mucin-producing tumor of the pancreas with an intraductal ultrasonographic system.

The purpose of this study is to examine the usefulness of intraductal ultrasonography at a frequency of 20 or 30 MHz in the diagnosis of mucin-producing tumor. The subjects were 66 patients with mucin-producing tumor (10 with main pancreatic duct type tumor and 56 with branch type tumor) who had also undergone endoscopic ultrasonography. In main pancreatic duct type tumors, we could diagnose the extent of the tumor and evaluate the invasion of the tumor into the pancreatic parenchyma in all seven patients who had undergone resection (three invasive tumors, four noninvasive tumors). Sixteen of 32 resected branch type tumors showing mural nodules with intraductal sonography were carcinoma or adenoma. On comparing intraductal and endoscopic ultrasonography in the rate of detecting nodules, in five tumors (one carcinoma and four adenomas), nodules were detected only with intraductal ultrasonography. In conclusion, intraductal ultrasonography is very useful for the diagnosis in the main pancreatic duct type tumor and in the detection of mural nodules in the branch type tumor.

Adenoma↗
PubMed1997

Reversal of multidrug resistance-associated protein-mediated drug resistance by the pyridine analog PAK-104P.

Three agents, verapamil, cepharanthine, and 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1, 3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-3-py ridinecarboxylate P-oxide (PAK-104P), that reverse drug resistance in P-glycoprotein (P-Gp)-mediated multidrug-resistant cells were examined for their activity to reverse drug resistance in multidrug resistance-associated protein (MRP)-mediated multidrug-resistant C-A120 cells. Agents other than PAK-104P could not reverse the resistance to doxorubicin in C-A120 cells. PAK-104P moderately reversed the doxorubicin resistance. In contrast, PAK-104P almost completely reversed the resistance to vincristine (VCR) in C-A120 cells as well as in KB-8-5 cells, and other agents moderately reversed the VCR resistance in C-A120 cells. PAK-104P at 10 microM enhanced the accumulation of VCR in C-A120 cells to the level of that in KB-3-1 cells without the agent. PAK-104P competitively inhibited the ATP-dependent [3H]leukotriene C4 uptake in membrane vesicles isolated from C-A120 cells. These findings demonstrate that PAK-104P can completely reverse the resistance to VCR in both P-Gp- and MRP-mediated multidrug-resistant cells and that PAK-104P directly interacts with MRP and inhibits the transporting activity of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Comparison of long-term survival between bone marrow transplantation and maintenance chemotherapy for adult acute lymphoblastic leukemia in first remission].

To clarify the efficacy of allogeneic bone marrow transplantation (BMT) for adult ALL in first remission we retrospectively studied long-term outcomes of adult ALL patients of age between 15 and 44 years who were treated in our institute from 1980 to 1990. In this period thirteen patients with HLA compatible donors were offered allogeneic BMT during the first remission, while 16 patients without HLA-compatible donor were treated with maintenance chemotherapy (Cancer Chemoth Pharmacology 33:359-365, 1994). Patient and disease characteristics (age, leukocyte count at presentation, immunophenotype, Ph1 chromosome, and duration to first remission) in the two groups were not significantly different (chi-square test p > 0.1). As causes of treatment failure, relapse was 90% for chemotherapy while relapse and therapy-related death were 67% and 33%, respectively, for transplantation. The leukemia-free survival (LFS) rates at 10 years were 52 +/- 13% for transplantation and 30 +/- 11% for chemotherapy (P > 0.2, g-Wilcoxon, Logrank). The 10-year-LFS rates of Ph1-negative patients of 15 to 29 year-old were 67 +/- 15% for transplantation (n = 9) and 62 +/- 15% for chemotherapy (n = 8) (P > 0.9). Although the present data are derived from a non randomized retrospective study and a relatively small number of patients, this study revealed no superiority of BMT over chemotherapy for the prolongation of first remission in adult ALL, especially, in a standard risk group such as young patients without Ph1 chromosome.

Adolescent↗
PubMed1997

[ATP-dependent glutathione conjugate export pump].

KCP4 cells are resistant to cisplatin and have a GS-X pump different from MRP. The GS-X pump was suggested to be involved in reducing the accumulation of cisplatin in KCP-4 cells. The expression of cMOAT was 4-to 6-fold higher in KCP-4 cells and two other cisplatin-resistant human cell lines. It is still not clear whether the cisplatin resistance in KCP-4 cells are attributed to cMOAT. Other members of the MRP/GS-X pump family have been reported. Amino acid sequence of EBCR of rabbit is 91% identical to that of human cMOAT. On the view of cancer chemotherapy, it is very important to understand the structure and function of GS-X pumps since they may be involved in not only drug resistance but also drug metabolism and side effects.

ATP-Binding Cassette Transporters↗
PubMed1997

[Induction chemotherapy based on histoculture drug response assay for a patient with advanced thymic cancer--a case report].

Histoculture drug response assay (HDRA) was applied to a biopsy specimen of advanced thymic cancer from a 68 years-old male patient. HDRA revealed that the tumor was not sensitive to CDDP but highly sensitive to 5-FU, ADM and MMC, which were administered as induction chemotherapy. The tumor regressed to 14% of the pretreatment size and was able to be completely resected with right and left brachiocephalic veins, superior vena cava, pericardium, right phrenic nerve and a part of right lung. Histologically, only a few small cancer nests remained in the fibrous tissue. The patient is alive and disease free 32 months after surgery. This result suggests that HDRA is useful to select anticancer agents which are sensitive to a rare kind of carcinoma such as thymic cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Mediastinal lymph node metastasis from esophageal carcinoma: CT assessment with pathologic correlation].

Computed tomographic (CT) scans were performed in 179 patients with esophageal carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings were compared with CT findings in a total of 7,218 resected lymph nodes. First, the criterion for lymph node metastasis on CT scans was 10 mm or more in long transverse diameter. The overall sensitivity and positive predictive value (PPV) were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of each of the eight subgroups of mediastinal nodes revealed that the PPV was more than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups. Second, the criterion for metastasis was 10 mm or more in short transverse diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26 of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106 nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long transverse diameter increased sensitivity to only 55%. Of the 317 histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the 6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size. Small (less than 5 mm in size) metastatic nodes were present in all eight subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size) nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We conclude that CT does not provide an accurate assessment of metastatic versus non-metastatic mediastinal lymph nodes in patients with esophageal carcinoma.

Esophageal Neoplasms↗
PubMed1996

Expression of the multidrug resistance-associated protein (MRP) gene in urothelial carcinomas.

The intrinsic or acquired resistance of urothelial cancer to chemotherapy is one major obstacle to successful treatment. Generally, the expression level of P-glycoprotein in urothelial cancer is low, so we accordingly investigated the expression of multidrug resistance-associated protein (MRP). We examined the expression of MRP mRNA by means of slot-blotting samples of 11 renal pelvic and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC). We also estimated, by Southern blotting, whether or not the MRP gene was amplified in clinical specimens that overexpressed MRP mRNA. MRP was detected immunohistochemically using a polyclonal antibody against MRP. In all, 5 of 11 renal pelvic and/or ureter tumors (45.5%), 17 of 33 bladder tumors (51.5%) and 4 of 7 non-cancerous urothelia of TCC patients (57.1%) expressed more than 2-fold the MRP mRNA levels of drug-sensitive human KB cells. There was no significant difference in the MRP mRNA level between primary and recurrent tumors. Low-grade urothelial carcinomas (G1 and G2 TCCs) expressed significantly higher levels of MRP mRNA than the high-grade G3 TCC. The MRP gene was not amplified in urothelial carcinomas, irrespective of their expression levels of MRP mRNA. Immunohistochemically, MRP was located mainly on the plasma membrane, but also detected on the cytoplasm of cancer cells. MRP may be one mechanism responsible for intrinsic drug resistance in low-grade urothelial cancer.

ATP-Binding Cassette Transporters↗
PubMed1996

Off-oscillation in hair cell membrane is correlated with the decremental response at the hair cell-afferent fibre synapse in the goldfish sacculus.

In this study, we examined the decremental response in the hair cell-afferent fibre synapse of goldfish. This decremental response is a transient reduction in sound-evoked EPSPs associated with a step reduction in sound intensity. To determine its presynaptic correlates, a patch clamp study was performed on oscillatory-type hair cells isolated from the sacculus of goldfish. Injection of depolarizing current produced a damped oscillation in the membrane potential of such cells. When the current intensity was reduced in steps, instead of simply being turned off, very marked dips were produced as off-oscillation in the hair cell membrane potential. These dips correlated with the decremental response in EPSPs.

Afferent Pathways↗
PubMed1996

Inwardly rectifying currents in hair cells and supporting cells in the goldfish sacculus.

1. Inwardly rectifying ionic currents were studied using patch-clamp recording methods in oscillatory-type and spike-type hair cells and supporting cells dissociated from the goldfish sacculus. These cells had different types of inwardly rectifying currents. The biophysical properties of these currents were investigated. 2. A unique potassium current (Isc) was the sole ionic current recognized in supporting cells. Isc was active throughout the membrane potential range between +30 and -170 mV, but showed weak inward rectification and no inactivation. 3. In spike-type hair cells, inwardly rectifying current (Ik1) was selectively permeable to K+ (K+:Na+ permeability ratio, 1:0.0021). Ik1 could underlie the high negative resting potential of these hair cells because it is partially active at this potential. The strong inward rectification of Ik1 contributed to the low negative plateau potential seen in spike-type hair cells. 4. In oscillatory-type hair cells, hyperpolarization-activated potassium-sodium current (Ih), which had properties similar to that in photoreceptor and other neurons, was present instead of inwardly rectifying K+ current. 5. In the cell-attached and inside-out modes with 125 microM external K+ ([K+]o), IK1 channel had a unitary conductance of 27 pS and showed inactivation with increasing hyperpolarization. Putative Ih and Iso single channels had unitary conductances of 7 and 61 pS, respectively, in the cell-attached mode with 125 microM Ko+.

Animals↗
PubMed1996

Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells.

An active efflux pump for cis-diamminedichloroplatinum(II) (cisplatin) has been identified in cisplatin-resistant KCP-4 cells isolated from human epidermoid carcinoma KB-3-1 cells. The adenosine triphosphate(ATP)-dependent transport of leukotriene C4 (LTC4), an endogenous substrate for the glutathione S-conjugate export pump(GS-X pump), has been found in membrane vesicles prepared from KCP-4 cells. Multidrug resistance-associated protein (MRP) has also been identified as an ATP-dependent LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 transporting activity of GS-X pump expressed in KCP-4 cells with that of MRP. The level of MRP gene expression in KCP-4 cells was low and similar to that in KB-3-1 cells. MRP was not detected in membrane vesicles prepared from KB-3-1 and KCP-4 cells by immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 transport in KCP-4 vesicles was more inhibited by 2,4-dinitrophenyl-S-glutathione(DNP-SG), bis-(glutathionato)-platinum(II) (GS-platinum) complex and glutathione disulfide(GS-SG) and less by LTD4 compared with that in C-A120 vesicles. The character of the LTC4 transporter expressed in KCP-4 vesicles is similar but not identical to that of MRP. Our results suggest that a glutathione S-conjugate export pump which is different from MRP exists in cisplatin-resistant KCP-4 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Requirement of multiple DNA-protein interactions for inducible expression of RNR3 gene in Saccharomyces cerevisiae in response to DNA damage.

The RNR3 gene encodes the large subunit of ribonucleotide reductase. Transcription of this gene is induced 12-fold in response to DNA damage or by a DNA replication blocker. To investigate cis-acting regulation, deletion analysis of the promoter region of the RNR3 gene was performed and we identified two upstream-repressing sequences in the RNR3 regulatory region. An 18-base-pairs fragment, termed DNA-damage responsive element 1 (DRE1) located between -212 and -194 in this region was found to be essential for the induction of RNR3. This fragment contained a negatively acting sequence where a protein factor bound to the region during normal growth but disappeared by exposure to 4-nitroquinoline-1-oxide. The other repressive element homologue to DRE1 was located at -263 to -254. One possible upstream-activating sequence which regulates the basal expression of RNR3 was also found. These results show that at least three potential cis-elements are necessary for the inducible expression of yeast expression of yeast RNR3 in response to DNA damage.

4-Nitroquinoline-1-oxide↗
PubMed1996

Expression of the multidrug-resistance-associated protein (MRP) gene in human colorectal, gastric and non-small-cell lung carcinomas.

MRP has been identified as another multidrug-resistance (MDR) gene and may be involved in an alternative MDR mechanism in some solid tumors. We investigated the expression of MRP mRNA in multidrug-resistance KB sublines (KB-8-5, KB-C2, C-A40 and C-A120), human non-small-cell lung carcinomas (NSCLC), gastric and colorectal carcinomas, and compared it with that in drug-sensitive human KB cells. MRP gene expression was elevated in 8 of 9 (89%) squamous-cell carcinomas of the lung. Furthermore, MRP expression in 4 squamous-cell carcinomas (L13, 18, 19 and 20) was more than 3.6 times higher than in KB-3-1 cells, and the average MRP mRNA expression level of all squamous-cell carcinomas was significantly higher than that of adenocarcinoma of the lung and of colorectal and gastric carcinomas. These results suggested that the MRP is responsible, at least in part, for drug resistance in some squamous-cell carcinomas of the lung.

ATP-Binding Cassette Transporters↗
PubMed1996

Mouse coproporphyrinogen oxidase is a copper-containing enzyme: expression in Escherichia coli and site-directed mutagenesis.

We previously isolated cDNA for mouse coproporphyrinogen oxidase (CPO) and provided evidence for the induction of mRNA during differentiation of murine erythroleukemia cells (Kohno et al. (1993) J. Biol. Chem. 268, 21359-21363). To better understand the structure and the mechanisms of reaction of the enzyme, we expressed mouse CPO in Escherichia. coli and purified it to a homogeneity. Analysis of the metal content revealed that the recombinant mouse CPO contains one copper atom per polypeptide chain. When the bacterial cells were treated with D-penicillamine, a copper chelator, formation of the active CPO was partially reduced. Addition of Cu2+ in minimal medium resulted in 6-fold higher level of CPO activity. These results suggest that expression of active mouse CPO in E. coli depended on the presence of Cu2+ in the culture medium. To elucidate the apparent involvement of Cu2+ in enzyme function, a series of mutant enzymes, whose highly conserved histidine and cysteine residues were individually converted to alanine residue, were prepared by site-directed mutagenesis. Mutant enzymes were expressed in E. coli and their activities examined. Mutation at histidine 158 resulted in a complete loss of enzyme activity, yet the enzyme protein was expressed at a comparable level. Concomitantly, only a trace amount of Cu2+ was detected in the purified H158A enzyme. We propose that mouse CPO is copper-containing enzyme and Cu2+ interacts with a conserved histidine residue.

Amino Acid Sequence↗