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Y Ino

Publications and source records attributed to Y Ino.

At least 73 records · Page 4Linked to original sources
PubMed1989

Low incidence of point mutation of c-Ki-ras and N-ras oncogenes in human hepatocellular carcinoma.

We examined the incidence of point mutation in codons 12, 13 and 61 of c-Ki-ras and N-ras genes in human hepatocellular carcinoma (HCC) using the polymerase chain reaction and oligonucleotide hybridization techniques. Among 34 tissues specimens surgically resected from 30 patients and 5 cell lines of human HCC, only two had ras point mutations; in one case, codon 12 of c-Ki-ras was altered from GGT, coding glycine, to GTT, coding valine; in the other case, codon 61 of N-ras was altered from CAA, coding glutamine, to AAA, coding lysine. Thus, point-mutational activation of ras oncogenes is an uncommon event in human HCC.

Carcinoma, Hepatocellular↗
PubMed1989

Characterization of the proteases in the crude mite extract.

Characterization of the proteases was performed in the crude mite extract fractionated by Sephacryl S-200 gel filtration. Three peaks of protease activities were detected in the fractions. From the results of substrate specificity and susceptibility to the inhibitors, PK.1 protease (about 60 kD) is suggested to be a trypsin-like protease of mites. From the results of susceptibility to various agents, PK.2 (about 30 kD) and PK.3 (about 20 kD) proteases may be cysteine proteases, e.g., papain and cathepsin B. PK.3 protease existed in the precipitate of 60% ammonium sulfate fractionation. The data in the present study suggest the possibility that Dermatophagoides farinae I allergen might be a cysteine protease probably derived from the gastrointestinal tract of the house dust mite.

Allergens↗
PubMed1989

Experimental asthma in guinea pigs sensitized with mites (Dermatophagoides farinae).

Guinea pigs were intraperitoneally immunized with 1, 10, 100 or 1,000 micrograms protein of an extract from mites (Dermatophagoides farinae) incorporated with aluminium hydroxide gel 3 times every 28 days. Ten days after the last injection, a bronchial provocation test was performed by the use of the mite extract. The group immunized with 1 microgram protein produced very low levels of IgE-, IgG1- and IgG2 antibodies, and did not show asthmatic response upon the challenge. Although the group immunized with 10 micrograms protein showed higher rates of asthmatic onset than other groups, the sera of this group contained lower levels of IgE antibodies than the group immunized with 100 or 1,000 micrograms protein. However, the sera of the group immunized with 10 micrograms protein showed higher ratios of IgE/IgG1, IgE/IgG2 and lower ratios of IgG1/IgG2 antibodies than the sera of the group immunized with 100 or 1,000 micrograms protein.

Airway Resistance↗
PubMed1989

[Inhibitory effect of N-alpha-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) on angiotensin converting enzyme in vitro].

N-alpha-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. The present investigation describes its ACE and other enzymes inhibitory properties and compares it to those of captopril, MK-421 and MK-422 in vitro. MK-0521 inhibited rat pulmonary ACE by 50% (IC50) at a concentration of 3 nM and was 6.13 times more potent than captopril. The IC50 values of MK-421 and MK-422 against ACE were 2,000 nM and 3.5 nM, respectively. MK-0521 had practically no inhibitory activities against carboxypeptidase A, carboxypeptidase B, leucine aminopeptidase, papain, pepsin and trypsin. The kinetic study on the inhibitory activity of M-0521 against ACE using Lineweaver-Burk plots indicated that MK-0521 exerted competitive ACE inhibition. The dialysis study conducted on the ACE-MK-0521 complex revealed that the inhibitory effect of MK-0521 against ACE was reversible. In the guinea pig ileum, MK-0521 potentiated the contractile effect of bradykinin and depressed the contractile effect of angiotensin I. These effects on bradykinin and angiotensin I were 33.11 and 2.63 times more potent than that of captopril, respectively. The present results suggest that MK-0521 may show a potent hypotensive effect in vivo.

Angiotensin I↗
PubMed1989

[Angiotensin converting enzyme inhibitory activity of MK-0521 in vivo and antihypertensive effect of its single oral administration on blood pressure and effect on the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs].

Angiotensin converting enzyme (ACE) inhibitory activity of MK-0521 in dogs and the effects of its single oral administration on blood pressure and the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs were compared with those of captopril and MK-421. MK-0521 at 0.001-0.1 mg/kg, i.v., or 0.01-1 mg/kg, p.o., attenuated the pressor effect of angiotensin I without affecting that of angiotensin II and augmented the depressor effect of bradykinin. The potency of MK-0521 to reduce the pressor effect of angiotensin I was 9.8 times that of captopril by intravenous administration, and by oral administration, it was 15.9-32.1 times that of captopril and approximately 3 times that of MK-421. When administered orally, the onset of action and the time to peak effectiveness were more rapid than those of MK-421, but slower than those of captopril. Duration of the action of MK-0521 was longer than that of captopril and equal or longer than that of MK-421. The inhibition of ACE was well correlated with serum MK-0521 levels. MK-0521 produced a dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive dogs at over 0.3 mg/kg, p.o., without affecting the heart rate. The antihypertensive effect of MK-0521 was persistent and approximately 3 times more potent than that of captopril. MK-0521 inhibited the serum ACE activity and increased the plasma renin activity, while it had a tendency to decrease plasma aldosterone level. These changes were parallel to the time course of the antihypertensive effect. These results suggest that the main mechanism of the antihypertensive effect of MK-0521 is the suppression of angiotensin II production due to the inhibition of the ACE.

Administration, Oral↗
PubMed1989

[Antihypertensive effect of repeated oral administration of MK-0521 in 2-kidney Goldblatt hypertensive dogs].

MK-0521 and captopril were orally administered to acute (6 to 8 days after unilateral renal artery constriction) and chronic (2 to 2.5 months after the constriction) 2-kidney Goldblatt hypertensive dogs for 7 to 21 days. MK-0521 lowered the blood pressure to similar extents in the acute and chronic stages of hypertension. The antihypertensive effect of MK-0521 was dose-dependent and persistent even after its cessation. Captopril also produced an antihypertensive effect, although the effect in the chronic stage of hypertension was less prominent than that in the acute stage of hypertension. MK-0521 was more inhibitory on the renin-angiotensin system than captopril. In the acute stage of hypertension, the dogs treated with MK-0521 had increased angiotensin converting enzyme (ACE) activity, while they had decreased plasma angiotensin II level and elevated plasma angiotensin I level and plasma renin activity. These results clarified the inhibitory effect of MK-0521 on ACE. In contrast, in the chronic stage of hypertension, MK-0521 showed no depression of plasma angiotensin II. There were no significant changes in daily urinary volume, and renal clearances of sodium, potassium and creatinine. These results suggest that the major mechanism of the antihypertensive effect of MK-0521 in 2-kidney Goldblatt hypertensive dogs is an inhibition of the ACE. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanisms of maintaining blood pressure between the two stages of 2-kidney Goldblatt hypertensive dogs.

Administration, Oral↗
PubMed1989

Production of IgE antibodies to mite in guinea pigs by nasal immunization.

There has been no report that IgE antibodies can be raised in guinea pigs by immunizations through respiratory tracts. We dropped a 0.1 ml mixture of 50 micrograms mite extract and aluminium hydroxide gel (Alum) into each of both nostrils of 5 guinea pigs. A mite extract alone was dropped into the nostrils of another 5 guinea pigs. The immunization was done every week. IgE antibodies were detected in one of guinea pigs sensitized 5 times with Alum + mite and also in another guinea pig in the same group sensitized 10 times. No IgE antibodies were detected in the animals immunized with mite alone.

Alum Compounds↗
PubMed1989

Dogs hypersensitive to house dust mite.

Active intradermal skin reaction, respiratory resistance and respiratory patterns were examined in five dogs after intradermal injection or inhalation of house dust mite (Dermatophagoides farinae) extract and the results obtained were as follows: 1. Three out of the five dogs exhibited positive skin reactions against house dust mite extract solution at concentrations of 0.1 micrograms/ml to 10 micrograms/ml. 2. Inhalation of mite extract at a concentration of 1 mg/ml by the dogs that had positive skin reactions produced a marked increase in respiratory resistance and changes in spirogram. These results suggest that the dogs that exhibited positive skin reactions were spontaneously sensitized to D. farinae.

Animals↗
PubMed1988

Increasing incidence of hepatocellular carcinoma possibly associated with non-A, non-B hepatitis in Japan, disclosed by hepatitis B virus DNA analysis of surgically resected cases.

At the National Cancer Center Hospital in Japan, the total number of surgically treated hepatocellular carcinomas (HCCs) has been increasing steadily and rapidly over the last 10 years, whereas the number of cases positive for hepatitis B surface antigen in sera (HBsAg) has remained almost stable. Thus, the relative percentage of HCC cases with serum HBsAg has shown a marked decrease. In order to examine whether this increased proportion of HBsAg-seronegative patients carries hepatitis B virus (HBV) DNA in the liver, we extracted DNA from the formalin-fixed and paraffin-embedded cancerous and noncancerous liver tissues of 79 patients with HCC. The HCCs examined included 49 specimens resected during a period from 1970 to 1980 and 30 resected in 1986 and 1987. We were able to detect reliably the presence of HBV DNA by dot-blot hybridization. The presence of HBV DNA in liver tissues showed a good correlation with positivity for serum HBsAg in both examined groups. In total, HBV DNA was detected in 81% (21 of 26) of HBsAg-seropositive cases and in only 8% (4 of 53) of HBsAg-seronegative cases, indicating that the increased number of HBsAg-seronegative cases had no HBV involvement. Among these HBsAg-seronegative HCC patients, 89.7% showed a histology of cirrhosis or chronic active hepatitis in the noncancerous liver and 29.1% had a history of blood transfusion. These results suggest an increasing incidence of non-A, non-B hepatitis-associated HCCs in Japan and the possible transmission of factors by means other than blood transfusion.

Carcinoma, Hepatocellular↗
PubMed1988

[Estimation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5-FU concentrations in sera and resected specimens from patients with ovarian tumors].

Concentrations of HCFU and 5-FU in blood and tissues of resected specimens were evaluated in 28 patients with ovarian tumor (pathologically benign 10, malignant 18) preoperatively considered to be malignant. 1) No significant difference of HCFU and 5-FU concentrations in sera, uterus and peritoneum was observed between the benign and cancer groups. 2) No significant difference of HCFU concentration in tissues of ovarian tumor was recognized between the benign and malignant groups, but as for 5-FU concentrations, 0.116 +/- 0.198 micrograms/g tissue in the cancer group was considerably higher than 0.021 +/- 0.144 micrograms/g tissue in the benign group (p = 0.085). Furthermore, the 5-FU level in ovarian cancer tissues was much higher than that in the tissues of the contralateral normal ovary, suggesting that degradation of 5-FU might be delayed in cancer tissue. 3) HCFU concentration in omental tissues from cancer patients was 0.043 +/- 0.061 micrograms/g tissue, significantly higher than that from benign patients, 0.004 +/- 0.008 micrograms/g tissue (p = 0.024). As for 5-FU concentration, no apparent difference was found, suggesting that 5-FU might be quickly eluted or metabolized in omental tissue.

Administration, Oral↗
PubMed1988

[Augmentative effects of radiofrequency hyperthermia (RFH) combined with intraperitoneal (IP) administration of CDDP in ovarian cancer].

Radiofrequency hyperthermia (RFH) was applied to 21 adnexal cancer patients in combination with IP administration of CDDP (150 to 200 mg) 2 weeks or more after surgery. The instrument used, an OMR-ON HEH 500C, was shown by rectal temperature monitoring to produce sufficient intraperitoneal temperature elevation up to 40 degrees-41 degrees C. The serum level of filterable CDDP after IP infusion of CDDP (150 mg) followed by sodium thiosulfate rescue was basically the same irrespective of whether RFH was used. It reached a peak level of 2.06 +/- 0.48 micrograms/ml (n = 8) 1h after IP infusion, and gradually declined thereafter. No serious side effect except 3 cases of II- to III-degree burns was recognized. A slight increase in the incidence of prolonged vomiting and diarrhea was found with the RFH combination. This suggests an exacerbating effect of RFH on intestinal damage following CDDP infusion. As for any suppressive effect on reaccumulation of ascites, RFH might have a slight benefit in increasing the antitumor effect of CDDP in 90% of patients.

Body Temperature↗
PubMed1987

Inhibitory effects of FUT-175, a new synthetic protease inhibitor, on intravascular hemolysis by human serum in mice.

Effects of FUT-175, a new protease inhibitor, on intravascular hemolysis of mouse erythrocytes caused by intravenous injection of human serum was studied in mice. In in vitro experiments, unsensitized erythrocytes obtained from various species of animals were lysed with sera in EGTA-GVB-Mg++. After heat inactivation of sera at 50 degrees C for 30 min, hemolysis in EGTA-GVB-Mg++ was abolished, indicating loss of activity of the alternative complement pathway. FUT-175 inhibited the alternative complement pathway-mediated hemolysis with IC50 values of 1.3 X 10(-7) to 4.0 X 10(-7) M. Intravenous injection of human serum caused intravascular hemolysis of mouse erythrocytes in mice. No remarkable change was observed in the mice that were injected with heat-inactivated (56 degrees C, 30 min) human serum. Intravenous administration of FUT-175 at a dose of 3 or 10 mg/kg inhibited intravascular hemolysis of mouse erythrocytes regardless of whether it was administered before or after injection of human serum. These results indicated that FUT-175 prevents intravascular hemolysis of mouse erythrocytes through the inhibitory effect of both alternative and classical complement pathway.

Animals↗
PubMed1987

Effects of FUT-175, a novel synthetic protease inhibitor, on the development of adjuvant arthritis in rats and some biological reactions dependent on complement activation.

1. The effects of FUT-175 on the development of adjuvant arthritis in rats were studied and compared with those of indomethacin. FUT-175 inhibited both primary and secondary paw lesions in the adjuvant arthritic rats when it was administered orally on a daily basis from the day before through 18th day after adjuvant injection. 2. In addition, FUT-175 inhibited the increase in hemolytic complement in adjuvant arthritic rats in a dose-dependent manner. 3. Indomethacin also showed an inhibitory effect on the development of arthritic lesion, but had no effect on the increase in hemolytic complement in the adjuvant arthritis in rats. 4. Furthermore, FUT-175 inhibited the activities of various proteases in vitro, and then strongly inhibited complement-mediated hemolysis via the classical and alternative pathways, while indomethacin had no effect on them. 5. These results suggest that the anti-inflammatory activity of FUT-175 may differ from indomethacin in the mechanisms of action and, at least in part, due to the anti-complement activity.

Animals↗
PubMed1987

Expression of Lewis blood group antigens in cancerous and non-cancerous liver.

The expression of Lewis blood group antigens, Lewisa, Lewisb, Lewisx and Lewisy, in 40 non-cancerous livers and in 20 hepatocellular carcinomas (HCC), 5 cholangiocarcinomas (CC), and 6 combined hepatocellular and cholangiocarcinomas (Comb) was studied by immunohistochemistry using monoclonal antibodies. Although normal hepatocytes did not express any of the four Lewis antigens, Lewisy expression was detected in some hepatocytes at the periphery of pseudolobules in cirrhotic liver. While Lewisx in bile duct epithelial cells was undetectable in normal livers, it was detected in some cases with non-cancerous liver diseases. Lewisx and Lewisy were detected in 30% of HCC and 100% of CC and Comb. Non-cancerous bile duct epithelial cells in almost all instances were stained strongly by anti-Lewisa and/or anti-Lewisb antibody. Proliferating bile ductules within Glisson's sheath and pseudolobules could be clearly detected by Lewisa and Lewisb staining. Lewisa and Lewisb were never detected in non-cancerous hepatocytes, and were only rarely detected in HCC, but were expressed in most cases of CC and Comb. These results suggested that Lewisa and Lewisb are useful markers for differentiation towards biliary epithelial cells in the liver, and that Lewisx and Lewisy expression might be associated with states of increased or altered cell proliferation.

Adenoma, Bile Duct↗
PubMed1987

[Side effects and anti-cancer effects following intraperitoneal (ip) administration of mitomycin C (MMC)].

Nineteen patients with gynecological cancers were initially treated intraperitoneally with MMC at a dose of 20 to 52 mg/body and then intravenously with CAP regimen. The following side effects were observed in patients intraperitoneally administered doses of MMC greater than 25 mg/m2; leucocytopenia 7/12, thrombocytopenia 5/12, liver damage 8/12, renal damage 2/12, ileus 3/12 and severe anorexia 2/12. Sixteen patients were evaluated for their prognoses more than 1 year after treatment. Seven of them are well with no sign of recurrence, but 9 suffered recurrence with or without peritonitis carcinomatosa (PC). The incidence of PC among these 9 cases was not linked with clinical staging, complete or incomplete resection or the dose of MMC administered, but rather with the respective histopathology; mesonephroid 2/2, metastatic 2/2, mucinous 1/1, serous 0/3, endometrial corpus 0/1. The results suggested that the former 3 kinds of cancer did not respond to i.p. infusion of MMC, whereas the latter 2 were sufficiently sensitive to MMC to prevent the occurrence of PC.

Female↗