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Biomedical subjects

K Ino

Publications and source records attributed to K Ino.

At least 55 records · Page 3Linked to original sources
PubMed1994

Expression of aminopeptidase N on human choriocarcinoma cells and cell growth suppression by the inhibition of aminopeptidase N activity.

We previously found that an aminopeptidase inhibitor, ubenimex (bestatin), had a growth-suppressive effect on choriocarcinoma cell lines in vitro. To clarify the mechanism of this action, we investigated the expression of aminopeptidase N (AP-N/CD13) on choriocarcinoma cells and other human tumor cells. Two choriocarcinoma cell lines, NaUCC-4 and BeWo, had higher AP-N activity than other cell lines (358.8 and 340.2 nmol/h/10(6) cells, respectively), as did human myeloid leukemia cell line, HL-60 (373.8 nmol/h/10(6) cells). These choriocarcinoma and leukemia cell lines with abundant AP-N activity showed much higher sensitivity to bestatin (IC50 = 0.5, 2.1 and 1.0 micrograms/ml, respectively) than the other cell lines. By immunoblotting and immunocytochemical staining, AP-N was detected as an approximately 165-kDa protein and localized on the cell membrane in choriocarcinoma cells. We also examined the effects of two other aminopeptidase inhibitors and three anti-CD13 monoclonal antibodies (MAbs) (WM15, MCS2 and MY7) on the growth of NaUCC-4 cells. Cell growth was markedly suppressed by the AP-N inhibitor actinonin as well as bestatin, but not by the AP-B inhibitor arphamenine. Of the three MAbs, only WM15, which is able to inhibit AP-N activity, suppressed cell growth in a dose-dependent manner. These results indicate that AP-N inhibitors show a growth-suppressive effect, presumably through inhibition of the enzymatic activity of AP-N on tumor cells, and suggest that AP-N may play important roles in the growth of certain tumors, such as choriocarcinoma and leukemia.

Antibodies, Monoclonal↗
PubMed1993

Tumoricidal effect of human macrophage-colony-stimulating factor against human-ovarian-carcinoma-bearing athymic mice and its therapeutic effect when combined with cisplatin.

The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM-CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect.

Agranulocytosis↗
PubMed1993

Possible action of human placental aminopeptidase N in feto-placental unit.

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.

Amino Acid Sequence↗
PubMed1993

Effects of triiodothyronine on canine hepatic ischemia caused by Pringle's maneuver.

BACKGROUND: A significant reduction in the serum concentration of triiodothyronine is frequently observed in surgical stress and may influence the severity and prognosis of the underlying disease. METHODS: Alterations of thyroid hormone levels and effects of triiodothyronine were evaluated in the shock state after Pringle's maneuver for 60 minutes in dogs. Triiodothyronine (1 micrograms/kg/hr) was infused intravenously for 3 hours after declamping in the triiodothyronine-treated group. The effect of triiodothyronine on hepatic mitochondrial function was investigated by measuring the arterial ketone body ratio (AKBR). RESULTS: In the control group (n = 6) the low triiodothyronine syndrome was observed and progressive deterioration of AKBR and standard liver functions represented by aspartate aminotransferase, glutamic-pyruvic transaminase, and lactic dehydrogenase were noted after declamping. All dogs went into shock and died within 24 hours. By contrast, in the triiodothyronine-treated group (n = 6), hemodynamics were stabilized and standard liver functions were maintained favorably (p < 0.01). AKBR was fully restored to the preischemic liver within 30 minutes after declamping, with a decrease in serum lactate levels (p < 0.05). All dogs survived at least 7 days after operation (p < 0.01). CONCLUSIONS: These results indicate that triiodothyronine has beneficial effects on cytoprotection, hemodynamics, and hepatic energy metabolism in the ischemic liver injury. Furthermore, it improves survival in the shock state after Pringle's maneuver.

Animals↗
PubMed1992

Bone metastases of hepatocellular carcinoma after liver resection.

Between January 1985 and July 1990, 323 cases of hepatocellular carcinoma underwent liver resection in our department. Bone metastases were found in 12 of these cases (3.7%). Bone metastases were mainly found in vertebral bone (58.3%) and pelvic bone (41.7%). The time interval to the development of bone metastasis after liver resection was closely related to the presence of intrahepatic metastasis and the stage at operation. In all cases, the initial clinical symptom was pain and/or motor disturbance. Radiotherapy was performed in 10 cases and transcatheter arterial embolization or surgery was performed in 4 cases. The pain or neurological symptoms improved with these therapies in all cases. Cumulative survival was 1 year in 74%, 2 years in 34%, and 3 years in 17%, respectively.

Adult↗
PubMed1992

Prophylactic effect of bestatin on the onset of invasive mole--clinical and fundamental studies.

This study was performed to determine whether bestatin (Ubenimex) has clinical prophylactic effects on the onset of invasive mole and a direct inhibitory effect on the growth of hydatidiform molar cells. A total of 49 patients with hydatidiform mole treated at Nagoya University Hospital from 1984 to 1990 were randomly divided into two groups, a bestatin administered-group and a bestatin non-administered group. Patients in the bestatin group were given 30 mg of bestatin orally and daily for three months just after their molar deliveries. There was no significant difference in age, gravidity, parity and gestational weeks between the two groups. There was also no significant difference in the duration of human chorionic gonadotropin (hCG) negative conversion in patients without invasive mole between the two groups. However, the incidence of invasive mole in the bestatin group (2/25, 8%) was significantly lower than that of the non-bestatin group (7/24, 29.2%). Nevertheless, there was no significant difference between the two groups in such immunological parameters as PHA skin test, PPD skin test, PHA stimulation index (PHA-SI), white blood cell (WBC) count lymphocytes % per WBC, OKT 3% per lymphocytes, OKT 4% per lymphocytes, OKT4/OKT8 and Leu 11% per lymphocytes. In vitro studies were performed with primary cultured hydatidiform moles. The result was that bestatin inhibited the secretion of hCG and 3H-thymidine uptake of hydatidiform molar cells. Thus, a possibility was suggested that bestatin directly inhibits the growth of hydatidiform molar cells and prevents the onset of invasive mole.

Adolescent↗
PubMed1992

Maintenance of liver graft viability in the state of brain death. Synergistic effects of vasopressin and epinephrine on hepatic energy metabolism in brain-dead dogs.

The influence of vasopressin and epinephrine on hepatic energy metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) and hepatic energy charge (EC) in brain-dead dogs. Mean arterial blood pressure (MABP) was significantly decreased from 125.5 +/- 5.5 to 53.4 +/- 1.7 mmHg after complete brain death (P less than 0.01). In the control group AKBR and EC were maintained at near the normal values thereafter, despite marked hypotension. Combined administration of vasopressin and epinephrine sustained AKBR normally and improved MABP above 90 mmHg (P less than 0.01). EC was also maintained within the normal range at 5 hr after initiation of administration of the drugs. By contrast, vasopressin or epinephrine alone maintained AKBR and EC at near the normal values, but improved MABP just slightly to around 60 mmHg (P less than 0.01). As for the volume control, the urinary output was significantly smaller in the vasopressin and epinephrine-treated group than in the control group (P less than 0.05). It is suggested that combined administration of vasopressin and epinephrine has a synergistic effect in improving the hemodynamics and maintenance of the energy status of the liver. This regimen is recommended as a good one for maintaining potential liver donors in the state of brain death.

Adenine Nucleotides↗
PubMed1992

Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death.

The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.

Animals↗
PubMed1992

Evaluation of ketogenesis in seriously reduced hepatic mitochondrial redox state. An analysis of survivors and non-survivors in critically ill hepatectomized patients.

Ketogenesis was evaluated in 33 critically ill hepatectomized patients in relation to the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate), which reflects hepatic mitochondrial redox state. In 15 patients whose arterial ketone body ratio decreased to below 0.4, blood ketone body levels were significantly increased concomitant with marked increase of blood lactate and plasma alanine levels. In the 6 survivors of these 15 patients, the arterial ketone body ratio was restored within the next 2 days, and blood ketone body levels were decreased. By contrast, in the nine non-survivors, the arterial ketone body ratio remained below 0.4, and blood ketone body levels were decreased, accompanied by significant increases in blood lactate and plasma alanine levels in the terminal stages. These results suggest that ketogenesis acts as an alternative process for ATP synthesis in the liver in critically ill patients. Death occurs when the liver falls into an energy crisis concomitant with the cessation of ketogenesis.

Adult↗
PubMed1992

[Reliability of a long-term recall method of dietary survey].

A total of 493 male inpatients were subjects in a study of the dietary intake (food frequency) when they were elementary school age and at the time of marriage by a long-term recall method. In order to examine the reliability of the recalled dietary data, 21 food items were compared with results of the National Nutrition Survey for the same time period. Food intake by the long-term recall method, especially meats, egg, milk and rice correlated well with the results of the National Nutrition Survey. From these results it appears that long-term recall of dietary intake frequency data averages are similar to the results of the National Survey data. Therefore the long-term recall method reflects the dietary practices of that era, and keeping in mind its limitations, its use as a means of revealing the dietary practices of a population is suggested.

Diet Surveys↗
PubMed1991

Growth inhibitory effect of bestatin on choriocarcinoma cell lines in vitro.

Bestatin, one of the biological response modifiers (BRMs), is an inhibitor of aminopeptidase B (AP-B), leucine aminopeptidase (LAP) and aminopeptidase M (AP-M). In this report, we investigated the direct effect of bestatin on the growth of cancer cells in vitro using established four choriocarcinoma cell lines. In vitro chemosensitivity was evaluated by the succinate dehydrogenase inhibition (SDI) test. Bestatin showed the growth-inhibitory effect on all the choriocarcinoma cell lines dose-dependently, especially on NaUCC-4 cells. Both an isomer of bestatin with no inhibitory activity against aminopeptidases, (2R, 3S)-AHPA-(R)-Leu, and another isomer with stronger inhibitory activity against AP-B than bestatin, (2S, 3S)-AHPA-(R)-Leu, did not show growth inhibition on NaUCC-4 cells. So it is suggested that one of the possible mechanisms responsible for the direct action of bestatin on the choriocarcinoma cells may be related to the inhibition of activity of LAP or AP-M rather than that of AP-B. Furthermore, cytotoxicity of actinomycin D on the choriocarcinoma cells was significantly enhanced by combination with bestatin. These results suggest that bestatin has not only an indirect host-mediated anti-tumor activity, but also a direct growth-inhibitory effect on some kinds of cancer cell lines.

Aminopeptidases↗
PubMed1991

[Extensive liver resection according to redox theory].

Postoperative mortality and morbidity are determined by intraoperative stress calculated by changes in arterial ketone body ratio (AKBR) during hepatectomy. In this report, we introduced two types of operative procedure which aims not to decrease AKBR during operation. One is total vascular exclusion (HVE) for liver resection using venovenous bypass which improved the deleterious effects of portal pooling and decreased return of blood to heart. The other is the hepatic resection applying the technique used in the transplantation from the living related donor. In this procedure, the remnant liver works for decreasing the intraoperative stress. The tumor involving lobe is removed under cold perfusion and the tumor is removed on the back table. Then, the tumor free liver is transplanted to the same position.

Carcinoma, Hepatocellular↗
PubMed1990

The outcomes of the operated hepatocellular carcinoma patients.

During the past 5 1/3 years, we have performed 521 hepatic resections, of which 308 cases were hepatocellular carcinomas (HCC). Two hundreds and sixty cases of the 308 HCC patients were studied on their outcomes. These patients included 198 males and 62 females, whose ages ranged from 29 to 84 years. Underlying cirrhosis of the liver was found in 66% of the patients. Hepatectomized patients were classified into 5 groups according to the curability as follows; Group A, the resection of the tumor-bearing segment and additional segment; Group B, the complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, the complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, the incomplete resection of the tumor; Group E, the surgical approach for advanced HCC with tumor thrombi in the main trunk or the 1st branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D and E was 14 (5.4%), 105 (40.4%), 61 (23.4%), 14 (5.4%) and 66 (25.4%), respectively. There were 5 death (2.6%) among the 194 patients of Group A-D within 30 days after operation and 12 death (18.2%) in Group E. The overall 5-year survival rate of all 249 patients except for 11 surgical death cases was 32%. Whereas, 5-year survival rate for Group A and B were 100% and 47%, 4-year rate for Group C was 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Clinical investigation of hepatectomies for hepatocellular carcinoma--significance of extended hepatectomy for advanced hepatocellular carcinoma].

Although the diagnostic methods for hepatocellular carcinoma (HCC) are now being improved, there are still many cases detected at advanced stage. We, based on the Redox theory and using a technique of vascular surgery and liver transplantation, made it possible to perform the extended hepatectomy more actively even in the advanced cases which were previously considered to be in-operable. We report these extended hepatectomies in this paper. From January 1985 to August 1989, we performed 263 hepatectomies for HCC. Out of these 263 cases, we examined 208 cases which had an interval more than three months from the time of the operation and had exact follow-up data at the end of August 1989. There are 57 extended hepatectomies and they consist of 4 groups as follows. 1) Multiple group (14 cases): the operation for the cases with multiple daughter nodules in both lobes besides the main tumor. 2) Thrombus group (30 cases): the operation for the cases with portal tumor thrombus in the first branch or the main trunk of portal vein. 3) IVC group (4 cases): the operation adding resection and reconstruction of IVC because tumor was hardly fixed to the wall of IVC. 4) Recurrence group (9 cases): the operation for hepatic recurrence. Six cases of the Multiple group survived more than one year and one case is still alive more than two years after surgery. The 6-months, 1-year and 2-year cumulative survival rates of the Multiple group are 50.5%, 38.3%, and 8.5% respectively and these results are better than other reports. Forty-three hepatic recurrences were observed in 138 cases whose tumor was completely resected macroscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗