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Biomedical subjects

K Okui

Publications and source records attributed to K Okui.

At least 37 records · Page 2Linked to original sources
PubMed1992

A novel anticancer treatment for xenoplanted human gastric cancer using polyamine antimetabolites in a low polyamine diet.

The aim of the present study was to evaluate a new anticancer treatment for gastrointestinal cancer, using a combination of polyamine antimetabolites, an anticancer agent and a low-polyamine state. Two polyamine antimetabolites, given as either 40 mg/kg of methylglyoxal-bis-guanylhydrazone (MGBG) or ethylglyoxal-bis-guanylhydrazone (EGBG) and a normal diet (ND), or 20 mg/kg of each drug and a low polyamine diet (LPD), together with 1,000 mg/kg of alphadifluoromethylornithine (DFMO) were administered ip to nude mice for six consecutive days. Mitomycin C (MMC) at 2 mg/kg was then given ip for 3 alternate days. The combination of MGBG or EGBG with DFMO plus MMC resulted in an enhanced antitumor efficacy on LPD. However, the combination which included EGBG was much more enhanced than that which included MGBG and there was no evidence of any tumor regrowth. Weight loss was minimal or nil in the mice given the combination with EGBG, but was evident in those given the combination with MGBG. These results led to the conclusion that in mice, the combined therapy of EGBG with DFMO plus MMC and LPD is a safe and effective regimen for the treatment of gastric cancer.

Adenosylmethionine Decarboxylase↗
PubMed1992

Isolation and mapping of 88 new RFLP markers on human chromosome 8.

To obtain new RFLP markers for construction of a high-resolution map of human chromosome 8, a cosmid library was constructed from a somatic hybrid cell that contained chromosome 8 as the only human component in mouse genomic background. Eighty-eight new RFLP markers were isolated and characterized, and 71 of them were sublocalized to chromosomal bands by fluorescent in situ hybridization (FISH). Of these, 36 were localized to the short arm, 34 to the long arm, and 1 to the centromeric region. Five markers defined VNTR loci. This work represents the first extensive isolation and physical mapping of RFLP markers on human chromosome 8. These new markers will serve as useful resources for linkage mapping of loci for inherited diseases and for efforts to identify a putative tumor suppressor gene(s) on chromosome 8.

Autoradiography↗
PubMed1992

Detailed mapping around the breakpoint of (3;8) translocation in familial renal cell carcinoma and FRA3B.

As a critical step toward cloning the breakpoint of the (3;8) translocation observed in familial renal cell carcinoma and a common fragile site on chromosome 3p (FRA3B), we have characterized the 3p14 region containing the breakpoint and FRA3B by fluorescence in situ hybridization (FISH), pulsed-field gel electrophoresis (PFGE), and genetic linkage analysis. Of 23 cosmids mapped by FISH, 14 cosmids were distal to the breakpoint of t(3;8) and 9 were proximal. Analyses of FRA3B by FISH were identical to those for the (3;8) breakpoint and indicated that the breakpoint of t(3;8) occurred at or very close to the fragile site. We have also constructed a genetic linkage map and a preliminary long-range restriction map using PFGE of the 3p14 region. The linkage results were consistent with the physical data. The combined results of FISH, PFGE, and linkage analysis establish a basis for further experiments to clone the (3;8) breakpoint and FRA3B.

Animals↗
PubMed1992

Isolation and mapping of 68 RFLP markers on human chromosome 6.

We have isolated 68 new RFLP markers on human chromosome 6. Of these, 64 were localized on chromosomal bands by the fluorescent in-situ hybridization (FISH) method, 25 on the short arm and 39 on the long arm. Their distribution was uneven; the markers were localized predominantly in regions of R-positive banding. Eleven markers defined VNTR loci. This expanded collection of DNA markers will contribute to high-resolution linkage mapping of genes causing inherited disorders and will provide useful reagents for isolation of putative tumor-suppressor genes on chromosome 6 that appear to be involved in malignancies. Furthermore, the new markers will be guideposts for detailed linkage and physical maps of this chromosome.

Blotting, Southern↗
PubMed1992

[Studies on stable control of blood sugar by continuous administration of insulin through isolated intestinal loop].

Insulin (INS) has been known to be absorbed through the intestine in small amounts and to decrease blood sugar (BS) levels. However, stable control of BS has not been attained by intestinal intake of INS. To elucidate the possibility of a surgical approach to control hyperglycemic states, Thiry-Vella loops or upper jejunal loop fistulae were constructed in mongrel dogs in hyperglycemic states. Hyperglycemic states (around 400mg/dl) were induced by injecting streptozotocin. Lente insulin was administered every day to control hyperglycemia, except for the days for studies. As we confirmed that co-administration of aprotinin (TR) or nafamostat mesilate (FT) was necessary, to decrease BS by infusing INS into the intestinal loops, safe and effective dose levels were determined by series of preliminary infusion studies in the intestinal loops of diabetic dogs. By continuous infusion of these doses into the jejunal loop fistulae, a long term stable blood sugar control was attained in the diabetic dogs as long as 7 days. These results suggest that continuous infusion of INS with antiproteolytic adjuvants like TR or FT into the isolated small intestinal loop can control BS in hyperglycemic states.

Animals↗
PubMed1992

[Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur in inoperable and recurrent gastric cancer].

Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur were analysed on 43 cases with inoperable and recurrent gastric cancer. Antitumor effect was observed only in one case (2%). Other clinical effects such as improvement of performance status (PS), appetite or pain were observed in 18 cases (42%). Decrease of serum IAP was observed in 25 cases (58%) and increase of albumin was observed in 20 cases (47%). The changes of these two factors seemed to be reversely correlated. Among 30 cases which didn't show decrease of albumin, we found no increase of serum-IAP in 22 cases (72%). In the cases which showed decrease of serum IAP from abnormally high level (more than 500 mu/ml) and increase of albumin from abnormally low level (less than 3.5g/dl), prolonged life span was observed by comparison with the other cases. The cases with any clinical effect contained 78% of the cases without increase of serum IAP, and 72% of the cases without decrease of albumin. These results suggested that life prolongation effect or improvement of clinical symptoms by our therapy was closely related to the change of these serum factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Effect of prostaglandin E1 derivative on labilization of liver lysosomal membrane in partial liver ischemia].

The change of liver lysosomal enzymes in tissue and serum during a reperfusion period was studied in partial liver ischemic model in rats and effect of Prostaglandin E1 (PGE1) derivative on partial liver ischemia was investigated. Partial liver ischemia was induced by clamping the branches of the vessels to the right and caudate lobes of rat liver. The clamp was released after 30 minutes of ischemia. Ischemic and nonischemic lobes of the liver were separately removed and the serum was also collected immediately and two hours after the release of the clamp. Lysosomal enzyme activities from free and bound lysosomal fraction were measured separately and the fragility index (F.I.) was calculated. PGE1 derivative was administered intraperitoneally 24, 6, 0.5 hours prior to the induction of ischemia at each dose of 0.05 microgram/kg. Pretreatment with PGE1 derivative prevented lysosomal labilization in ischemic lobe, since there was a significant decrease in F.I. of cathepsin D in the PGE1-pretreated group (preischemia; 28.3 +/- 2.4%, immediately after reperfusion; 30.3 +/- 2.5%, two hours after reperfusion; 30.3 +/- 2.5%) compared to the placebo group (immediately after reperfusion; 40.9 +/- 3.4%, two hours after reperfusion; 41.7 +/- 3.4%, p less than 0.05, p less than 0.05, p less than 0.01, respectively). Pretreatment with PGE1 derivative also significantly suppressed the increase of serum lysosomal enzyme activity. These results showed that PGE1 derivative improved liver lysosomal labilization in partial liver ischemia.

Alprostadil↗
PubMed1992

[Adequate requirements of energy and protein in postoperative total parenteral nutrition].

Adequate requirements of energy and protein in post operative total parenteral nutrition (TPN) were determined by studying the effects of energy and protein dose on nitrogen retention at varying levels of surgical stress assessed by urinary excretion of total catecholamines. Fifty-two patients received esophagectomy (severe stress), and gastric or colorectal operations (moderate stress) fed exclusively by TPN perioperatively were divided into 6 groups according to the dose level of protein and energy; Group I: 40 kcal, 1.0 g.protein/kg.day (9 patients), Group II: 40 kcal, 1.5 g.protein/kg.day (11 patients), Group III: 40 kcal 2.0 g.protein/kg.day (8 patients), Group IV: 40 kcal, 3.0 g.protein/kg.day (7 patients), Group V: 30 kcal, 2.0 g.protein/kg.day (11 patients), and Group VI: 50 kcal, 2.0 g.protein/kg.day (6 patients). Daily nitrogen balance (NB) and urinary excretion of total catecholamines (U-CA) were determined everyday pre- and post-operatively. Significantly negative correlations between U-CA and NB were observed. Statistically significant differences among the correlations of all groups were recognized. In moderate stress, increasing dose of protein and energy improved NB, and positive NB was achieved when 1.5-2.0 g.protein/kg.day with 35-40 kcal/kg.day was provided. Protein dose exceeding 3.0 g/kg.day caused the rise of BUN. In severe stress, such as following esophagectomy, NB was not improved by increasing dose of nutrients.

Aged↗
PubMed1992

[Changes in lysosomal enzymes and cell damage of the liver in obstructive jaundiced rats].

The changes of hepatic lysosomal enzymes and the hepatic cellular damage were investigated in rats with obstructive jaundice, phospholipase A2 (PL-A2) which is a strong labilizer of lysosomal membrane was added in the lysosomal fraction of rat's liver with various concentration. The activities of cathepsin D and beta-glucuronidase those were released by PL-A2 from lysosomal fraction were measured. The values of both lysosomal enzyme activities showed positive relation to the concentration of PL-A2, and were remarkably increased in obstructive jaundiced rats than in normal rats. We also measured the activity of cathepsin D released by Triton X-100 from lysosomal fraction of normal and jaundiced rat liver. The amount of lysosomal enzyme was more increased in obstructive jaundiced liver than in normal liver. Fragility score as the indicator for lysosomal membranous fragility was calculated as the ratio of cathepsin D released by PL-A2 to that released by Triton X-100. Fragility score was more increased in obstructive jaundiced rats than in normal rats. In conclusion, these data suggest that the fragility of lysosomal membrane could be enhanced in obstructive jaundiced liver.

Animals↗
PubMed1992

[An experimental study of myonephropathic metabolic syndrome (MNMS)].

We have attempted to establish dog experimental model similar to clinical MNMS. Thirty-five dogs were divided into four groups; G-1: Ligation of abdominal aorta. (N = 5), G-2: Ligations as above for 6 hours and reperfusion. (N = 12), G-3: Same as G-2+ligation of superior epigastric arteries (N = 13), G-4: Same as G-2+transection of abdominal muscles (N = 5). Biochemicals, electrolytes and blood gas analysis in artery and vein were measured before, 6 hours after clamp, 5 minutes, 1 hour, 6 hours after reperfusion. Skeletal muscle PCO2, pH of lower leg were continuously measured. In G-1, no dog showed MNMS, in G-2, half of the dogs developed MNMS, in G-3, MNMS developed 9, but not in 4. In G-4, 4 dogs died during aortic cross-clamping. Satisfactory results were obtained in G-3. From the results of statistical analysis, the measurement of GOT, LDH, CPK, Cr and tissue PCO2, pH showed high significance between MNMS (+) and (-), and had correlation with K, BE, pH of artery and vein after reperfusion. Therefore, we consider that above factors are appropriate predictors for MNMS.

Acidosis↗
PubMed1992

[Enhancement of anti-tumor effect of adriamycin by verapamil in a intrahepatic arterial infusion in the rats].

In a intrahepatic arterial infusion, the enhancement of cytotoxicity of adriamycin (ADR) by verapamil (VER), a calcium antagonist was investigated in male Wistar rat with liver tumor of Walker 256 carcinosarcoma. The accumulation of ADR in tumor tissue at 2 hrs after a bolus intrahepatic arterial injection of ADR with VER (4 mg/kg) was 1.9-fold more than without VER. But VER did not enhance it in normal liver tissue and heart tissue. In the continuous intrahepatic arterial infusion therapy (cia) of ADR and VER (1.5 mg/kg/day) for 6 days, tumor weight and the accumulation of ADR in tumor tissue, normal liver tissue and heart tissue were assessed. Tumor weight of ADR-cia+VER-cia group was significantly less than ADR-cia group (p less than 0.05). And the accumulation of ADR in tumor tissue of ADR-cia+VER-cia group was significantly higher than ADR-cia group (p less than 0.05). But VER did not enhance it in normal tissue. The administration of VER in a intrahepatic arterial infusion is shown to be able to enhance the cytotoxicity of ADR in tumor tissue but not to enhance in normal tissue. The continuous intrahepatic arterial infusion of VER enhanced cytotoxicity of ADR at clinical dose and it suggests the clinical applicability of VER in cancer chemotherapy.

Animals↗
PubMed1991

Stapled or manual suturing in esophagojejunostomy after total gastrectomy: a comparison of outcome in 379 patients.

From January 1983 to December 1989, we performed esophagojejunostomy on 379 patients who underwent total gastrectomy for gastric cancer. A mechanical EEA stapler or conventional manual suturing was used. The clinical outcomes of 199 patients in whom stapling was used (stapler group) and 180 patients in whom manual suturing was done (manual group) were compared. Two of the 199 patients in the stapler group and 3 of the 180 patients in the manual group died of causes directly related to the anastomosis. In the stapler group, 16 stapled anastomoses were formed supradiaphragmatically, and manual suturing was done for 6 patients. The highly placed anastomosis was formed without left thoracotomy or with median sternotomy in 8 of the 16 patients in whom the stapling device was used and in 1 of the 6 patients in whom manual suturing was used. The incidence of anastomotic leakage and stenosis did not differ between the groups. Thus, the mechanical stapler facilitated the construction of a rapid, reliable esophagojejunostomic anastomosis.

Aged↗
PubMed1991

A clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer.

Intraoperative pelvic hyperthermochemotherapy (IOPHC) with mitomycin C (MMC) was prescribed for 14 patients with resectable advanced rectal cancer in an attempt to prevent a postoperative local recurrence. Immediately after rectal amputation and extended lymphadenectomy, IOPHC was performed using physiologic saline containing 40 micrograms/mL of MMC at 45.5 +/- 0.6 C for 90 minutes, with an apparatus devised for IOPHC. At the end of IOPHC, the esophageal temperature was 37.2 +/- 0.8 C and cooling was not required. Antitumor efficacy and complications in the IOPHC group were compared with findings in 12 rectal cancer patients who underwent surgery only within the same period of time. Operation time was not prolonged with IOPHC treatment. In cytologic examinations of the pelvic lavage just before IOPHC treatment, viable cancer cells were detected in 6 of the 14 patients but were never detected in the postoperative exudate drained from the pelvic cavity. Of the 12 patients in the control group, 2 had a local recurrence, while in the IOPHC group there was no local recurrence for 16.9 +/- 9.7 months at this writing. Postoperative complications did not differ between the groups. This IOPHC treatment is a favorable method in eradicating cancer cells for postoperative local recurrence of rectal cancer.

Aged↗
PubMed1991

N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden.

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P less than 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.

Animals↗
PubMed1991

Lobular involvement in human breast carcinoma.

One hundred twenty-nine cases of breast carcinoma were examined in order to clarify the occurrence of lobular involvement with regard to stromal invasion. Lobular involvement was clearly recognized in 56 cases (43%) having discernible portions of intraductal carcinoma components. The process of lobular involvement was first recognizable as an extension of a few carcinoma cells from intralobular ducts into the acinar lumina. Progressive accumulation of the carcinoma cells resulted in marked swelling and distortion of the involved lobules. During the process, perilobular myoepithelial cells (actin-positive cells) were stretched and disappeared. Subsequently, breaks in the basement membranes were also observed, resulting in stromal invasion of carcinoma cells. The lobular involvement was classified into common and round varieties, possibly reflecting different growth activities of the carcinoma cells. The stromal invasion was initiated by peripheral budding or focal necrosis of the involved lobules. The latter pattern was often observed in comedo carcinoma. It was thus revealed that in breast carcinomas the terminal ductal-lobular units are quite often involved and can become sites of extraductal invasion.

Actins↗
PubMed1991

[Enhancement of selective drug accumulation and retention in normal and regenerating liver by the use of lipiodol in portal venous infusion in rats].

We studied selective accumulation and retention of lipiodol (LP) and anticancer agents in normal and regenerating liver tissue following portal infusion in rats. Total concentration of Aclarubicin (ACR) and its metabolites in liver tissue was higher in ACR + LP portal infusion group than in ACR portal infusion group both in normal and regenerating liver, concentration of active metabolites of ACR was higher in ACR portal infusion group than in ACR peripheral infusion group. Much higher concentration was found in ACR + LP portal infusion group. Histologic examination revealed more toxic effect on regenerating liver in ACR portal infusion group than in ACR + LP portal infusion group. Oil red staining demonstrated the retention of lipiodol more than 7 days following intraportal infusion in regenerating liver tissue. This study confirms that the ACR + LP portal infusion induces selective accumulation and long-term retention in normal and regenerating liver tissue, and may enhance the antitumor effect of drugs.

Aclarubicin↗
PubMed1991

[The effect of human growth hormone on protein metabolism in the surgically stressed state].

The effects of human growth hormone (HGH) on protein metabolism were investigated. In the experimental study, thirty one male SD rats receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after burn in HGH group was significantly higher than in control group. (p less than 0.05) Rates of whole body protein turnover (Q), together with those of synthesis (S) and breakdown (B) were significantly higher in HGH group than in control group. (p less than 0.01) Nitrogen balance significantly correlated with urinary total catecholamine excretion in both groups. (p less than 0.01) The difference of correlations of nitrogen balance to urinary total catecholamine excretion between two groups was statistically significant (p less than 0.01) when compared by analysis of covariance. In the clinical study, 12 patients after sub-total esophagectomy receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after operation in HGH group was significantly higher than in control group. (p less than 0.01) Q,S, and B were higher in HGH group than in control group. Increase of S was statistically significant. (p less than 0.01). These results indicate that HGH may be greatly beneficial in improving protein metabolism in the surgically stressed state.

Adult↗