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Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 325 records · Page 18Linked to original sources
PubMed1996

Differential diagnosis of gall-bladder masses using colour Doppler ultrasonography.

To evaluate the diagnostic accuracy of colour Doppler ultrasonography in the differential diagnosis of gall-bladder lesions, we studied colour Doppler flow imaging of gall-bladder masses in 75 patients with gall-bladder masses, including 26 patients with cancer, 18 with benign polyps, 10 with adenomyomatosis and 21 with pseudo-tumorous sludge and 28 healthy subjects as controls. The presence of a colour signal, pattern of the colour signal, blood flow velocity and resistive index (RI) within lesions were assessed using colour Doppler ultrasonography. In cancerous lesions, the colour signal pattern was diffuse or arborizing (sensitivity 90.5% (19/21); specificity 62.5% (10/16)) and the velocity and RI were (mean +/- s.d.) 39.0 +/- 12.4 cm/s and 0.62 +/- 0.12, respectively, which was significantly different (P < 0.01) compared with controls (11.4 +/- 2.5 and 0.75 +/- 0.03, respectively). The colour signal pattern obtained from polyps was linear at their base in 62.5% (10/16) of cases, but the velocity (13.6 +/- 5.5) and RI (0.74 +/- 0.08) did not differ from those of the controls. Lesions other than cancer and polyp had no colour signal. There were overlaps in the values of velocity and RI between malignant and benign lesions. When 20 cm/s for velocity and 0.65 for RI were used as the respective cut-off values, the sensitivity and specificity of this method in the diagnosis of malignant lesions was 95.2% (20/21) and 87.5% (14/16) for velocity and 66.7% (14/21) and 87.5% (14/16) for RI, respectively. In a prospective study consisting of 10 patients with cancer and 21 patients with polyps, the sensitivity and specificity were 90 and 66.7% for the colour signal, 100 and 100% for velocity and 80 and 90.4% for RI, respectively. In conclusion, colour Doppler ultrasonography can be useful in the diagnosis of gall-bladder masses in combination with conventional ultrasonographic findings of gall-bladder masses, especially in the differentiation of cancers from benign lesions.

Blood Flow Velocity↗
PubMed1996

Effects of PPADS and suramin on contractions and cytoplasmic Ca2+ changes evoked by AP4A, ATP and alpha, beta-methylene ATP in guinea-pig urinary bladder.

1. The contraction and intracellular Ca2+ change evoked by diadenosine tetraphosphate (AP4A) were studied in the outer longitudinal muscle of the guinea-pig urinary bladder and compared with those evoked by ATP and alpha, beta-methylene ATP (a P2-purinoceptor agonist). 2. AP4A, ATP and alpha, beta-methylene ATP produced concentration-dependent transient contractions. These contractions were inhibited by PPADS (pyridoralphosphate-6-azophenyl- 2'-4'-disulphonic acid), 0.3- 30 microM, a P2x-purinoceptor antagonist, and suramin, 1-300 microM, a P2-purinoceptor antagonist in a concentration-dependent manner. From Schild plot analysis, the apparent pA2 values for PPADS for contractions evoked by AP4A, ATP and alpha, beta-methylene ATP were 6.86, 6.56, 6.74, and those for suramin were 6.01, 4.59 and 5.12, respectively; the Schild slopes for PPADS were 1.07, 1.14 and 1.06, and, those for suramin 0.75, 1.05 and 1.16, respectively. 3. AP4A (10 microM) and ATP (100 microM) failed to elicit any contraction of the tissue after a desensitization produced by repeated application of alpha, beta-methylene ATP (1 microM). 4. In fluorescence experiments with fura-2, the increases in [Ca2+]i and contraction evoked by AP4A were suppressed by suramin and nifedipine, an L-type Ca2+ channel blocker. 5. These findings suggest that P2x-purinoceptors, which are more sensitive to PPADS than suramin, exist on the outer longitudinal muscles of guinea-pig urinary bladder, and that the AP4A-evoked contraction results from Ca2+ influx.

Adenosine Triphosphate↗
PubMed1996

Human trehalase: characterization, localization, and its increase in urine by renal proximal tubular damage.

By using polymerase chain reaction, cDNA encoding human renal trehalase has been isolated. The partial amino acid sequence deduced by the cDNA showed homologies in rabbit, Tenebrio molitor and silkworm trehalase. Northern blots showed renal trehalase mRNA to be about 2.0 kb. To examine the properties of renal and urinary human trehalase, the trehalase cDNA was inserted in the pMAL-cRI vector downstream from the malE gene, which encodes maltose-binding protein. Transfection of the recombinant pMAL-cRI in Escherichia coli provided high levels of expression of the maltose binding protein-trehalase fusion protein. A rabbit was immunized with purified fusion protein, and antihuman trehalase antibodies were obtained. Immunoblot analysis disclosed that renal and urinary trehalase exhibited a molecular mass of about 75 kDa. Analysis by indirect fluorescent microscopy demonstrated that the enzyme located in only proximal tubular cells. Urinary trehalase activity was low in the healthy infants and elevated in patients with asphyxia. Markedly high activity was observed in a patient with Lowe syndrome. The immunoreactive urinary trehalase with 75 kDa was increased dependent on the elevation of the activity. On the basis of these findings, we conclude that the increase of urinary trehalase reflects the extent of renal tubular damage, and we propose that urinary trehalase can be a specific marker of renal tubular damage.

Amino Acid Sequence↗
PubMed1996

Lung cancer cell lines inhibit leukotriene B4 production by human polymorphonuclear leukocytes at the level of phospholipase A2.

We studied cellular interactions between human polymorphonuclear leukocytes (PMN) and lung cancer cell lines by investigating the influence of cancer cells on the production of leukotriene B4 (LTB4) and superoxide anion (O2-) by stimulated PMN. Of the nine cancer cell lines established from human lung cancers that we examined, H23 cells showed the highest LTA4 hydrolase activity. When PMN were stimulated by the calcium ionophore A23187 in the presence of H23 cells, the production of LTB4, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), and 12(S)-hydroxyeicosatetraenoic acid (12-HETE) decreased in a dose-dependent manner. On the contrary, H23 did not inhibit O2- production by PMN. Two other cell lines (N417 and Q9) caused similar inhibition of LTB4 production by PMN. These three cancer cell lines alone did not generate any metabolites of the arachidonic acid (AA) lipoxygenase pathway or any O2- upon stimulation with A23187 alone. The addition of AA dose-dependently reversed the H23-induced inhibition of LTB4, 5-HETE, and 12-HETE production by PMN, suggesting inhibition at the phospholipase A2 (PLA2) level. Furthermore, addition of the cancer cell line Q9 inhibited 14C release from [14C]AA prelabeled PMN in a cell number-dependent manner in the buffer, with and without albumin. The supernatant of H23 cells also inhibited the production of LTB4 by PMN stimulated by A23187, as did the addition of H23 lysate or its 10(4) x g centrifugation supernatant. While neither the 10(5) x g supernatant (cytosol) nor the pellet (microsome) exhibited inhibitory activity, the combination of the separated cytosol and microsomal fractions restored the inhibitory activity. Furthermore, addition of the 10(4) x g supernatant of Q9 lysate to partially purified human cytosolic PLA2 inhibited PLA2 activity in a dose-dependent manner. Our results indicate that the lung cancer cell lines used in our study inhibit LTB4 production by human PMN through inhibition of phospholipase A2 activity, which may contribute to a predisposition to pulmonary infections in patients with lung cancer.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Elimination of low-osmolality contrast media by hemodialysis.

PURPOSE: To compare the dialyzability and safety of 2 types of low-osmolality contrast media administered to end-stage renal failure patients maintained on regular hemodialysis. MATERIAL AND METHODS: Of 44 CT examinations, iohexol was used in 22 and ioxaglate in the other 22. Adverse reactions and hemodynamic changes were recorded. Thirty minutes after the beginning of CT investigation, hemodialysis was commenced. Elimination rate and clearance of the contrast media were measured as indices of their dialyzability. RESULTS: After 4 hours of hemodialysis, 78.4+/-6.5% of iohexol and 72.4+/-6.0% ioxaglate were eliminated. Clearance of iohexol was higher than that of ioxaglate at all sampling times. No severe hemodynamic change nor adverse reaction were observed. Minor reactions were more frequently observed in the ioxaglate group. CONCLUSION: Iohexol, a nonionic monomeric contrast medium, is more advantageous for hemodialysis patients than ioxaglate, an ionic dimeric contrast medium.

Contrast Media↗
PubMed1996

Elimination of ioversol by hemodialysis.

PURPOSE: The dialysability of ioversol was investigated in 12 patients with chronic renal failure, on 4-h hemodialysis. MATERIAL AND METHODS: One hundred ml of ioversol (320 mg I/ml) was injected in less than 10 min during CT. Hemodialysis was commenced within 30 min of starting the contrast medium injection and was continued for 4 h. Blood was sampled before and at 15 min, 30 min, 1 h, 2 h, and 4 h after the start of hemodialysis. Mean dialysance of ioversol was 114 to 129 ml/min and the elimination rate was 82.5 +/- 5.1% 4 h after starting hemodialysis. The half-life of ioversol during hemodialysis was 1.80 +/- 0.38 h. The only side effects of the ioversol injection were heat sensations, which were experienced by 3 patients. RESULTS: As ioversol was effectively removed from the body during the 4 h of hemodialysis and no severe adverse reactions were observed, we conclude that ioversol is suitable for use in hemodialyzed patients.

Adult↗
PubMed1996

Functions of cardiac ion channels under normal and pathological conditions.

Using the patch clamp technique, normal and abnormal functions of cardiac ion channels were studied. The transient outward K+ current contributes to the early repolarization phase of the action potential as well as to the plateau height and total duration. The latter role is observed in at premature excitations due to slow recovery from inactivation of this current compared to that of the Ca2+ current. Early and delayed afterdepolarizations are produced by multiple components of ionic currents, especially in the former case. Transient inward current is mainly involved in the formation of delayed afterdepolarizations, but the activities can be produced by a different ionic mechanism in rare occasions. Barium-induced automaticity can be brought about by blocking and unblocking of the inward rectifier K+ channels. The ATP-sensitive K+ channels are assumed to play important roles in myocardial ischemia and related conditions. The channels are a target of the K+ channel openers and their functions are modulated by various intracellular factors. While the channel activity is strongly inhibited by intracellular ATP, ATP is necessary for the channel in an operative state. The former effect by ATP is produced by its ligand action, but the latter may be brought about by hydrolysis of MgATP, which may be regulated by the assembly and disassembly of the actin cytoskeleton.

Action Potentials↗
PubMed1996

Effects of the novel antipsychotic agent 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro -2(1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary gland.

The effects of a novel antipsychotic agent, 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2 (1H)-quinolinone (OPC-14597, generic name aripiprazole), on prolactin (PRL) release from isolated rat anterior pituitary slices and on the serum PRL levels were investigated in male rats. In in vitro experiments on the isolated anterior pituitary, the spontaneous PRL release was decreased by talipexole, a dopamine D2 receptor full agonist, in a dose-dependent manner to 36% of the basal release, and the decrease was antagonized by haloperidol, a D2 receptor antagonist. OPC-14597 also decreased the release of PRL at the same concentration range with a maximal decrease to 78%, the potency being weaker than that of talipexole. The decrease in PRL release induced by OPC-14597 was completely antagonized by haloperidol. Moreover, OPC-14597 antagonized the inhibition of PRL release induced by talipexole. In in vivo experiments, haloperidol increased the serum PRL levels to 8 times the basal PRL level, whereas talipexole decreased the levels to 49% of the basal level. OPC-14597 increased the serum PRL levels by 2-fold and also antagonized the talipexole-induced decrease. The hyperprolactinemia induced by estrogen, which was inhibited by talipexole but enhanced by haloperidol, was enhanced by OPC-14597, whereas the hyperprolactinemia induced by reserpine, which was inhibited by talipexole but elevated by haloperidol, was inhibited by OPC-14597. In addition, the OPC-14597-induced inhibition was antagonized by haloperidol. These results suggest that OPC-14597 has a mixed agonist/antagonist profile at D2 receptors on lactotroph cells and thereby exerts either an antagonistic or an agonistic action, depending on the preexisting tone of the dopaminergic neuronal activities.

Animals↗
PubMed1996

Non-neuronal release of ATP and inositol 1,4,5-trisphosphate accumulation evoked by P2- and M-receptor stimulation in guinea pig ileal segments.

Intracellular signal transduction involved in non-neuronal ATP release evoked by alpha, beta-methylene ATP and bethanechol was evaluated in guinea pig ileal longitudinal muscle segments. alpha, beta-methylene ATP (100 microM) and bethanechol (10 microM) evoked ATP released that reached a peak about 3 min after administration. The evoked release of ATP was markedly inhibited by neomycin and spermine, inhibitors of phospholipase C, but not by treatment with pertussis toxin. In addition, the release of ATP was almost completely suppressed by 1 mM Li+, an inhibitor of inositol monophosphatase. These inhibitors, however, did not affect the contractions of the tissue evoked by these agonists. Forskolin and phorbol 12-myristate 13-acetate, activators of adenylate cyclase and protein kinase C, respectively, failed to enhance the evoked release. The accumulation of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] in the muscle segments were enhanced about 2 min after the administration of alpha, beta-methylene ATP. In the presence of 1 mM Li+, however, the enhancement of Ins(1,4,5)P3 accumulation by the P2 agonist was no longer elicited. These findings suggest that the release of ATP by receptor stimulation may result mainly from the activation of phospholipase C, which is coupled to a pertussis toxin-insensitive G-protein and subsequent accumulation of Ins(1,4,5)P3 in the smooth muscles. However, the discrepancy between the inhibitory effects of Li+ on the release of ATP and the accumulation of Ins(1,4,5)P3 to be clarified in future studies.

Adenosine Triphosphate↗
PubMed1996

Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16.

Pancreatic cancer is one of the most lethal cancers in humans. The majority of these cancers arise from the pancreatic duct epithelium. Research into the pathogenesis of pancreatic carcinoma has largely relied on animal models. In vitro models of pancreatic carcinogenesis using propagable cultured epithelial cells derived from the pancreatic ducts of rats and hamsters have been described. A human model, however, has been nonexistent due to the unavailability of propagable cultured duct epithelial cells derived from normal human pancreas. We report here a reproducible method for the long-term culture of pancreatic duct epithelial cells derived from normal and benign adult human pancreata by infection with a retrovirus containing the E6 and E7 genes of the human papilloma virus 16. One of these cell lines has become immortal and has propagated continuously for more than 20 passages. They remain anchorage dependent in their growth and nontumorigenic in nude mice. These cell lines and the methodology described here to establish them may provide new avenues for in vitro studies of the roles played by duct epithelium in human pancreatic diseases and cancers.

Aged↗
PubMed1996

Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY.

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.

Antigens, CD↗
PubMed1996

[Clinicopathological study on primary lung cancer--immunohistochemical expression of p53 suppressor gene and bcl-2 oncogene in relation to prognosis].

Two hundred and eleven surgically resected primary lung tumors were studied immunohistochemically. According to histologic type, they were 129 adenocarcinomas, 56 squamous cell carcinomas, 4 small cell carcinomas, 8 large cell carcinomas, 8 adenosquamous cell carcinomas, 5 so-called carcinosarcomas and 2 other tumors. Immunohistochemical expression of p53 and bcl-2 was studied in relation to the disease-free survival. Among the 211 patients with lung cancer, 109 were positive for p53 expression, and there was no significant relationship between p53 expression and sex, or clinicopathological stage and size of the tumor, although the patients with squamous cell carcinoma had a significantly higher frequency of p53 expression than those with adenocarcinomas. The frequency of p53 expression was significantly higher in the patients with poorly differentiated adenocarcinomas than in those with other histologic types. Seventy four of the 211 patients were positive for bcl-2 expression and bcl-2 expression was higher in the stage I patients and patients with small lung tumors 2cm or less in diameter than in the other patients. The patients with adenocarcinoma had a higher frequency of expression than those with squamous cell carcinoma but no difference was found in the histological differentiation of the tumor. The 5-year survival of patients positive for p53 expression was poorer than that of those with negative expression and the survival rate was higher in the patients positive for bcl-2 expression than in those with negative expression. These findings suggested that the expression of p53 and bcl-2 is a useful marker of follow-up and prognosis, but will require more data concerning the mechanism of carcinogenesis. Seven cases of primary lung cancer were examined for genetic abnormality of the p53 gene. cDNA was synthesized from total RNA of primary tissues of lung cancer using oligo (dT) primer and reverse transcriptase and polymerase chain reaction (RT-PCR), and PCR-single strand conformation polymorphism (SSCP) analysis were performed. Five patients gave a positive result upon PCR-SSCP analysis of the p53 gene. To confirm the results of PCR-SSCP analysis, their nucleotide sequences were further analyzed and four of them had point mutations at different codons (154, 176, 207, 236) and one had deletion of one nucleotide (245) in exon 5 and 8. Fifteen percent of 26 patients with small peripheral lung adenocarcinomas less than 2cm in diameter were already advanced in stage and various factors such as vascular invasion, pleural involvement and degree of scar grade were higher than in patients with clinicopathological stage I. In advanced cases, the frequencies of p53 expression was higher than in stage I cases. Concerning the relationship of the degree of scar grade to PDGF-B expression, we demonstrated the production of PDGF-B protein immunohistochemically and the expression of PDGF-B-mRNA by In situ hybridization in the adenocarcinoma cells and macrophages of the lung tumors. However, no significant correlation was observed between the degree of PDGF-B expression and collagen production in the fibrotic focus.

Adenocarcinoma↗