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Y Katsuki

Publications and source records attributed to Y Katsuki.

At least 37 records · Page 2Linked to original sources

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer].

We evaluated the result of intra-arterial infusion chemotherapy on liver metastasis from gastric cancer. Of 92 cases of metastatic liver tumor, 17 cases received intra-arterial infusion chemotherapy after primary resection. For comparison, we assigned the 17 cases to two groups according to the infused agents. One group was treated with the combination therapy of 5-FU, epirubicin and MMC (FEM group: n = 7), and another with other antineoplastic agents (non-FEM group: n = 10). In the FEM group, the response rate, 1-year survival rate and 50% survival period were 33.3%, 51.4%, 430 days, respectively, while those of the non-FEM group were 10.0%, 10.0%. 147 days. Although there was no significant difference (p = 0.0951), improvements in survival rate and survival period were observed. This implies the possibility that intra-arterial infusion chemotherapy, especially the combination therapy of FEM, is an effective treatment for liver metastasis from gastric cancer.

Aged↗

[Complication due to arterial infusion chemotherapy for liver metastasis from colorectal cancer].

OBJECTIVES: Arterial infusion chemotherapy is considered to be an extremely effective treatment for liver metastasis from colorectal cancer in terms of its tumor reduction and preventing recurrence in residual liver after resection. However, there still remain some unclear points as to the influence on hepatic artery and bile duct when this treatment is used over the long term. We report some conclusions obtained by examining cases of hepatic arterial occlusion (stenosis) and biliary complication who received this treatment. MATERIALS AND METHODS: Thirty-six cases who received this treatment over 3 months were the objects of this study, with the aim of direct effect against metastatic focus (21 cases) and prevention of recurrence in residual liver (15 cases). The ages were from 27 to 81; 22 cases were male and 14 were female. Indwelling routes of catheter were gastroduodenal artery (GDA) in 28 cases and femoral artery (FA) in 8 cases. Intermittent high-dose infusion (WHF: 5-FU 1,000 mg/m2/5 hrs qw) was adopted as the method. RESULTS: Hepatic arterial occlusion or stenosis was observed in 12 cases (GDA: 10; FA: 2). There seemed to be no correlation with the total dosage of 5-FU or the number of administrations. Even when hepatic arterial occlusion or stenosis occurred, no change was observed in liver function, and there no death was caused by this. However, CT showed a low-density area followed by atrophy in the right lobe in one case with right hepatic arterial stenosis, despite normal portal blood flow. Of the 6 cases which developed obstructive jaundice, 4 were due to the increase of metastatic focus or lymph nodes, and 1 case without dilatation of bile duct died from suspected sclerosing cholangitis. In this case, ALP had been increasing since 1 month before the onset of jaundice. Another case which developed biloma accompanied by the increase of serum bilirubin improved by discontinuance of chemotherapy. CONCLUSION: Since arterial infusion chemotherapy for liver metastasis from colorectal cancer causes hepatic arterial occlusion (stenosis) at a high rate, early detection of abnormalities by liver function test and imaging diagnosis which leads to early treatment is important.

Adult↗

Role of urinary trypsin inhibitor in the maintenance of pregnancy in mice.

OBJECTIVE: To investigate the mechanisms whereby urinary trypsin inhibitor prevents lipopolysaccharide-induced preterm delivery in mice. METHODS: On day 15 of pregnancy, C3H/HeNCrg female mice impregnated by Crg:B6D2F1 male mice were treated intraperitoneally with lipopolysaccharide (50 micrograms/kg, twice at a 3-hour interval) to induce preterm delivery. Urinary trypsin inhibitor (2.5 x 10(4), 7.5 x 10(4), or 25 x 10(4) units/kg, ten times at 1-hour intervals) or saline solution was administered intraperitoneally to the animals. RESULTS: The incidence of preterm delivery was significantly decreased on a dose-related basis by urinary trypsin inhibitor treatment. Urinary trypsin inhibitor prevented the morphologic and functional changes in fetal membranes and cervical ripening preceding the onset of preterm delivery. Urinary trypsin inhibitor also suppressed the increase in plasma and amniotic fluid concentrations of interleukin-1 alpha, interleukin-6, and tumor necrosis factor-alpha after the lipopolysaccharide dosing in this animal model for preterm delivery. CONCLUSION: Urinary trypsin inhibitor prevents the pathogenicity of preterm delivery through the suppression of cytokine production.

Animals↗

Repeated administration of low-dose lipopolysaccharide induces preterm delivery in mice: a model for human preterm parturition and for assessment of the therapeutic ability of drugs against preterm delivery.

OBJECTIVE: Our purpose was to establish a new animal model for human preterm delivery for assessment of the protective effect of drugs against preterm delivery. STUDY DESIGN: C3H/HeN, C3H/HeN, and BALB/c female mice impregnated by C3H/HeN, B6D2F1, and B6D2F1 male mice, respectively, were treated intraperitoneally with Escherichia coli lipopolysaccharide (0 to 100 microgram/kg, single dose or repeated doses at 1- to 6-hour intervals) on days 12 through 17 of pregnancy. On day 15 of pregnancy, the C3H/HeN females that had been impregnated by B6D2F1 males and administered lipopolysaccharide were treated intraperitoneally with indomethacin (1000 microgram/kg), ritodrine hydrochloride (1000 microgram/kg), urinary trypsin inhibitor (25 x 10(4) units/kg), or gabexate mesylate (100 mg/kg); preterm or term delivery was recorded for these mice. RESULTS: C3H/HeN females impregnated by B6D2F1 males revealed the highest (100%) incidence of preterm delivery when the females were treated with 50 microgram/kg lipopolysaccharide twice at a 3-hour interval on day 15 or 17 of pregnancy. Indomethacin and urinary trypsin inhibitor used separately significantly decreased the incidence of preterm delivery, but only urinary trypsin inhibitor, and not any of the other drugs, significantly increased the incidence of term delivery in the mice. CONCLUSION: A new animal model for investigation of preterm delivery was established, and its usefulness for assessment of the protective effect of drugs against preterm delivery was demonstrated.

Animals↗

Usefulness of a new tactile sensor for measurement of uterine cervical ripening in mice in a quantitative and noninvasive manner.

OBJECTIVE: The purpose of this study was to establish a method with a new tactile sensor for determining in a quantitative and noninvasive manner the extent of uterine cervical ripening. STUDY DESIGN: We used a newly designed tactile sensor to measure the softness of the cervix in untreated nonpregnant, pregnant, parturient, and nursing mice and then on day 15 of gestation in pregnant mice treated with dehydroepiandrosterone sulfate or Escherichia coli lipopolysaccharide. Additionally, to elucidate the correlation between the extent of cervical softness and its morphologic changes, we observed microscopically the uterine cervices. RESULTS: The hardness of the murine cervix decreased with the progression of pregnancy and became minimal at delivery. We demonstrated for the first time with a tactile sensor for measuring hardness that dehydroepiandrosterone sulfate and lipopolysaccharide significantly decreased the stiffness of the murine cervix. These findings were supported by the morphologic observations on the cervices. CONCLUSIONS: These results show that the tactile sensor for measuring hardness makes it possible to determine the extent of cervical ripening quantitatively rather than qualitatively. We consider that cervical ripening determined objectively in this manner is a good parameter to predict the onset of preterm delivery.

Animals↗

[Effects of lacidipine, a new dihydropyridipine derivative, on various cerebral ischemia models].

We examined the cerebral protective effects of lacidipine (L) using three different types of cerebral ischemia models, and the effects were compared with those of nicardipine (N). (1) In the transient forebrain ischemia model of the rat, oral administration of L (0.3 and 1 mg/kg) before ischemia significantly decreased the number of acidophilic neurons in CA1 regions of the hippocampus 7 days after ischemia. N (3 mg/kg, p.o.) before ischemia also produced a significant reduction in the number of acidophilic neurons, and it's effectiveness was almost the same as that of L (1 mg/kg). (2) In the focal cerebral ischemia model of the rat, oral administration of L (1 and 3 mg/kg) before of after left middle cerebral artery occlusion (MCAO) significantly reduced infarct size at 24 hr after MCAO. Such an ameliorative effect was also observed when N was administered orally. However, the effect of N at 30 mg/kg was less than that of L at 1 mg/kg. (3) In the delayed cerebral vasospasm model of the dog after subarachnoid hemorrhage (SAH), intravertebral artery injection of L (10 micrograms/kg) or N (10 micrograms/kg) dilated the contracted basilar artery 3 days after SAH to the level before SAH. Finally, while both L and N increased cerebral blood flow (CBF) in a dose-dependent manner in conscious normal rat, the increment of CBF induced by L at a given level of reduced-blood pressure was greater than that induced by N. These results indicate that lacidipine may be a potential therapeutic agent that exerts a protective effect against brain damage after cerebral ischemia.

Animals↗

[The preventive effect of weekly high-dose 5-FU infusion (WHF) after resection of hepatic metastasis from colorectal cancer].

Hepatic metastasis is often found even after resection of hepatic metastases from colorectal cancer. This implies that the micrometastasis already existed in residual liver when the resection was performed, and so complete recovery with resection alone is rare. We have been using a weekly high-dose 5-FU HAI (WHF = 5-FU 1,000 mg/m2/5 hrs/qw) since 1991, which has preventive effects for metastasis in residual liver as compared to a group treated without infusion chemotherapy. Hepatectomy was performed in 30 of 113 cases of hepatic metastasis from colorectal cancer during the past 16 years. For comparison, we divided the 30 cases into group A1 (16 cases H1:12, H2:4), which received hepatectomy only, and group A2 (14 cases H1:8, H2:4, H3:2), which additionally received infusion chemotherapy. The 1- and 3-year (cumulative) survival rates were 64.6% and 32.3% in group A1, and 100% and 75.3% in group A2 respectively in which the treatment outcome was significantly higher. The 1- and 3-year recurrence rates were 41.7 and 66.3 in group A1, and 8.3% each in group A2, respectively, which reveals that metastasis in residual liver was controlled in group A2. Other metastases were seen in lung (6 cases), bone (2 cases), hepatic hilar lymph node (3 cases), brain (1 case) and local (3 cases) in group A1, while only one metastasis in each brain and locally was seen in group A2 so far. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect not only for the recurrence in residual liver but also for other metastases. Therefore, as improvement in the survival rate is expected.

Aged↗

[Preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer].

We compared 12 cases treated with intra-arterial chemotherapy (group A), with 15 cases only undergoing the usual hepatectomy (June 1991-February 1995). Six cases in group A were H1, 4 were H2, and 2 were H3; 12 cases in group B were H1, and 3 were H2. In both groups, primary lesions were removed. All cases received high-dose intermittent 5-FU infusion (WHF) at 1,000 mg/m2 via a reservoir for 5 hours a week at the outpatient clinic. Cumulative survival rates for 1 and 3 years are 100% and 68.6%, respectively, in group A, and 58.7% and 25.2% in group B, which indicates the treatment outcome in group A was significantly better. Recurrence in residual liver was not found in group A except for one case whose tumor was unremoved, but it was found in 8 cases (53.3%) in group B up to this writing. CEA value after resection in group A was within the normal range except for one case with a local recurrence. It seems that intra-arterial 5-FU infusion chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer has a preventive effect on residual liver, and the improvement of the cumulative survival rate can be expected.

Aged↗

[Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on elasticity and endothelium-dependent relaxation of the aorta in high cholesterol diet-fed rabbits].

We studied the elasticity and endothelium-dependent relaxation (EDR) of the aorta in 1% cholesterol diet (HCD)-fed rabbits. Furthermore, the effects of ethyl all-cis-5,8,11,14, 17-icosapentaenoate (EPA-E) were examined in this model of atherosclerosis. After 12 weeks of feeding with HCD, the animals showed increase in plasma total cholesterol level, formation of atherosclerotic plaque, decrease in aortic elasticity and impairment of EDR to acetylcholine (ACh). The levels of aortic elasticity in HCD-fed rabbits administered orally with EPA-E (300 mg/kg for 12 weeks) were almost the same as those of rabbits fed a normal diet, although EPA-E showed no effects on the plasma total cholesterol level and formation of atherosclerotic plaque in HCD-fed rabbits. On EDR in response to ACh and cyclic GMP formation in the HCD-fed rabbit aorta, EPA-E improved the impairment of these parameters, but not significantly. Therefore, EPA-E had little effect on the endothelium in this model of atherosclerosis, although EPA-E improved the decrease in the aortic elasticity. Because the levels of aortic elasticity showed no significant correlation with the magnitude of EDR to ACh or the size of atherosclerotic plaque, the decrease of aortic elasticity in this model of atherosclerosis was thought to have little relation to the dysfunction of the endothelium.

Acetylcholine↗

[A case of liver metastasis from bile duct cancer effectively treated with hepatic artery infusion chemotherapy].

We performed hepatic artery infusion chemotherapy (HAI) combined with 5-FU-MMC-EPIR for bile duct cancer metastasized to the liver. We report a case for which we obtained PR. The case was a 59-year-old woman, who was diagnosed to have multiple liver metastases with an increase of CEA and LDH after 6 months from absolute curative resection for middle bile duct cancer. The patient was catheterized into the proper hepatic artery through the right femoral artery, and 5-FU 500 mg qw, MMC 4 mg q2w, and EPIR 30 mg q4w were infused via a reservoir. Two months after the treatment was begun, CEA and LDH values became normal. At the same time, PR was obtained and was shown upon CT, which continued for 5 months. After an 8-month period during which the patient was an outpatient at PS-0, multiple bone metastases appeared, and the radiotherapy was combinedly utilized for each lesion. The side effect of this method was decrease of leukocytes and blood platelets, but it disappeared by discontinuing medication. The patient died two years after the first operation, a year and four months from the time HAI was begun. It was possible to continue this treatment with PS 1-2 on an outpatient basis until one month before the patient's death. We concluded that hepatic artery infusion chemotherapy is an effective therapeutic method.

Antineoplastic Combined Chemotherapy Protocols↗

Successful heterotransplantation of human endometrium in SCID mice.

OBJECTIVE: To establish an experimental system useful for long-term evaluation of human endometrial tissue by its heterotransplantation to SCID mice. METHODS: Human endometrium was transplanted subcutaneously into SCID mice, nude mice, or nude mice given anti-asialo GM1 antibody, a natural killer activity suppressor. The transplant was observed by ultrasonography for up to 10 weeks and then morphologically. To assess the drug susceptibility of the transplant, danazol (10-100 mg/kg/day orally), buserelin (0.01 mg/kg/day subcutaneously), or estradiol (0.5 mg/kg/day intraperitoneally) was administered to the host mice for up to 10 weeks after the transplantation. Multiple-comparison procedures were used for statistical evaluation. RESULTS: The heterotransplant was accepted 100% in SCID mice and natural killer activity-suppressed nude mice, but was significantly inferior (40%) in nude mice at 10 weeks after the transplantation. The transplant size was volumetrically measurable noninvasively by ultrasonography. Using this SCID mouse model, we could evaluate drug effects on the transplanted endometrium. CONCLUSION: This system in SCID mice may be useful for evaluating drug actions on human endometrium and endometriotic tissues.

Adult↗

Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on the physical properties of arterial walls in high cholesterol diet-fed rabbits.

The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on in vivo physical properties of arteriosclerotic aorta and femoral artery in high cholesterol diet (HCD)-fed rabbits were studied. The aortic pulse wave velocity (PWV) of rabbits fed HCD for 12 weeks (control group) tended to be higher than that of rabbits fed a normal diet (normal group). Because the PWVs in HCD-fed rabbits administered orally with 30 and 300 mg/kg/day EPA-E were significantly lower than the PWV of the control group, the distensibility of arteriosclerotic aorta was improved with administration of EPA-E. The stiffness parameter (beta) value as an in vivo indicator of arteriosclerosis was significantly higher in the control group than in the normal group and improved with administration of EPA-E to almost the same level as that of the normal group. The beta-values were in significant negative correlation with medial elastin content and medial smooth muscle cell (SMC) density in thoracic aorta and in positive correlation with the free cholesterol content in abdominal aortic SMC. On the other hand, they were not correlated with either the cross-sectional area of intimal thickening lesions or the plasma lipid levels measured simultaneously. The femoral PWVs were, like those in the aorta, higher in the control group as compared with the normal group, and the changes were improved with administration of EPA-E. These results show that EPA-E improved the in vivo distensibility of arteriosclerotic arteries in HCD-fed rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of highly purified ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on rabbit platelets.

The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), highly purified ethyl ester of icosapentaenoic acid (EPA), on rabbit platelets were studied. In in vitro, highly purified EPA (62.5-3000 microM) suppressed the platelet aggregation induced by collagen, arachidonic acid (AA) and adenosine diphosphate (ADP). In ex vivo, a single administration of EPA-E (300 and 1000 mg/kg, p.o.) and repeated administrations (30 and 300 mg/kg/d, p.o.) for 2 weeks showed no effects on collagen-, AA- and ADP-induced platelet aggregation. Repeated administrations (30 and 300 mg/kg/d, p.o.) for 4 weeks suppressed the collagen-induced platelet aggregation, but not the AA- and ADP-induced platelet aggregation. Repeated administrations for 4 weeks also suppressed thromboxane B2 (TXB2) formation induced by collagen, but a single administration and repeated administrations for 2 weeks failed to inhibit TXB2 formation. The EPA level in the platelet phospholipids increased slightly with a single administration, and increased markedly with repeated administrations for 2 and 4 weeks. The AA level in the phospholipids showed practically no changes with a single and repeated administrations. These results suggested that highly purified EPA-E could reduce platelet aggregability by the change of the EPA level in the platelet phospholipids and should allow for a reasonable period of administration.

Animals↗

[Intra-arterial chemotherapy with 5-FU (weekly high dose 5-FU HAI) for the prevention of tumor recurrence in residual liver after hepatic resection of metastasis from colorectal cancer].

Intra-arterial cancer chemotherapy using an implantable reservoir was performed for the prevention of tumor recurrence in residual liver after resection of a metastatic tumor from colorectal cancer. Four cases of synchronous hepatic metastases and one case of metachronous hepatic metastasis, which were in H1 (2 cases) and H2 (3 cases), were treated. 5-FU was administered in a dose of 1,000 mg/m2 5 hours weekly (weekly high dose 5-FU HAI). The longest survival obtained is 1Y 11M. Other cases have survived for 1Y 7M, 1Y 12M, 9M, and 3M. Tumor recurrence was not observed in all cases except one. This case had a residual tumor because the complete resection was impossible. The tumor recurrence rate in patients treated with surgery alone at Nikko Memorial Hospital (n = 11) was 63.6%. The 1- and 2-year survival rate in these patients was 60.6% and 26.9%, respectively. As compared to these rates, the results of this study were very favorable. Although mild nausea and abdominal discomfort were observed in 1 patient, this adverse effect was reduced by administration of an anti-ulcer agent. Only a slight decrease of WBC and PLT counts was observed. Consequently, for residual liver after resection of hepatic metastasis from colorectal cancer, this intraarterial chemotherapy with 5-FU is considered to be effective to prevent tumor recurrence and thus to prolong survival.

Aged↗

Synergistic stimulation of nitric oxide hemoglobin production in rats by recombinant interleukin 1 and tumor necrosis factor.

Nitric oxide (NO) is formed from arginine in Escherichia coli lipopolysaccharide (LPS) treated rat; however, none of specific cytokine inducing NO generation is yet determined. We studied the effect of interleukin 1 (IL-1) and tumor necrosis factor (TNF) on NO production in rats by detecting NO-hemoglobin in their blood, using electron spin resonance. Either IL-1 or TNF alone stimulated NO-hemoglobin formation. Combined administration of IL-1 and TNF markedly enhanced NO-hemoglobin generation, demonstrating the synergistic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of NO-hemoglobin production in rats than each alone.

Animals↗

Spin trapping study on the kinetics of Fe2+ autoxidation: formation of spin adducts and their destruction by superoxide.

The oxidation of Fe2+ was investigated by electron spin resonance spin trapping techniques with N-t-butyl-alpha-phenylnitrone (PBN) and dimethyl sulfoxide. Under pure oxygen, the spin adduct PBN/.OCH3 was rapidly generated by the addition of Fe2+ (0.2-1.2 mM) into phosphate buffer containing ethylenediaminetetraacetate (EDTA), dimethyl sulfoxide, and PBN at pH 7.4, but it decayed. The decay process of PBN/.OCH3 consists of two components. The fast decay was dependent on Fe2+ concentration. Another was due to destruction of the spin adduct by superoxide anion (.O2-), because superoxide dismutase (SOD) markedly prevented the decay. Catalase decreased the yield of PBN/.OCH3. When EDTA was replaced by diethylenetriaminepentaacetic acid (DTPA), both the generation and decay process of PBN/.OCH3 were slow. SOD and catalase effects were similar to those in EDTA. Fe2+ produced PBN/.OCH3 even in the absence of chelators. We could estimate the kinetic parameters by computer simulation, comparing the Fe2+ oxidation in EDTA with that in DTPA. These results demonstrate that Fe2+ reacts with O2 to generate .O2- and then H2O2, which produces .CH3 by reaction with Fe2+ and dimethyl sulfoxide.(.)OCH3 results from the reaction between .CH3 and O2. The adduct PBN/.OCH3 decays by reaction with Fe2+ and .O2-.

Air↗

[Intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa].

Intraperitoneal cancer chemotherapy using an implantable reservoir has been recognized as an effective treatment. In this report, we evaluate treatment results in 20 cases undergoing this chemotherapy and the correlation between reservoir-use period and cumulative survival rates. Twenty patients with an average age of 59.3 years were all observed to have peritoneal dissemination during operations in the period of January 1987 through January 1991. Their primary diseases were 10 cases of gastric cancer, 8 cases of colorectal cancer, 1 case of appendiceal carcinoma, and 1 case of malignant tumor of retroperitoneum. Intraperitoneal reservoirs were implanted in surgically-made pockets in subcutaneous lower abdomen, and their catheters were inserted into Douglas cul de sac. Medications used were CDDP, MMC, and 5-FU. The average number of administration was about 6 or 7, but, the maximum number was 67 in one case. Contrast media or RI infused via reservoirs was recognized to diffuse widely within the peritoneal cavity. Eighteen of 20 cases (90%) obtained good conditions to undergo ambulant treatments. The longest survival records were 827 days in a gastric cancer group, 639 days in a colorectal cancer group, and 326 days in a malignant tumor of retroperitoneum group. Two cases having the former two survival records are still alive at this writing. One case with appendiceal carcinoma is PS 0 and now under out-patient treatment at 2 years and 6 months after operation. The 50% survival period, and 6-month, 1-year, and 2-year cumulative survival rates were 8.8 months, 60%, 40.5%, and 37%, respectively in the gastric cancer group; and 13.5 months, 75%, 63%, and 31.5%, respectively, in the colorectal cancer group. On the contrary, 50% using period, and 6-month, 1-year, and 2-year cumulative using rates were 5.3 months, 40%, 10%, and 10%, respectively, in the gastric cancer group; and 7.9 months, 58%, 0%, and 0%, respectively, in the colorectal cancer group. Evaluation of the correlation between the reservoir use periods and cumulative survival rates has led to the conclusion that cumulative survival rates are extended significantly p = 0.0011 in each cancer group with more than 6 months treatment period compared to within each cancer group with less than 6 months treatment. 1) Intraperitoneal cancer chemotherapy using an implantable reservoir enables patients to receive treatment at outpatient clinics. 2) The continuous treatment for more than 6 months suggests the possibility for longer survival.

Cisplatin↗