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Biomedical subjects

Y Ogata

Publications and source records attributed to Y Ogata.

At least 91 records · Page 5Linked to original sources
PubMed1998

Phase II study of 5-fluorouracil, pirarubicin and low-dose consecutive administration of cisplatin for advanced and recurrent gastric cancer.

BACKGROUND: The FAP regimen was modified and low-dose consecutive daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU) and pirarubicin were employed to reduce the toxicity and achieve synergy. Patients with advanced and recurrent gastric cancer were treated with this regimen as early phase II trial and its efficacy and toxicity were assessed. METHODS: Twenty-nine patients with advanced or recurrent gastric cancer were treated with intravenous 5-FU, 360 mg/m2, continuous infusion, on days 1-5 and 8-12, CDDP, 10 mg/body, drip infusion, on days 1-5 and 8-12 and pirarubicin, 20 mg/body, on days 1 and 8, which was repeated every 4 weeks. RESULTS: One complete (CR) and 10 partial (PR) responses were observed. Eleven patients showed no change (NC) and seven had progressive disease (PD). The overall response rate (CR and PR) was 37.9%. The response rates of lymph node metastatic lesions and primary gastric lesions were 47 and 44%, respectively. The major toxicity was bone marrow suppression, which was well tolerated. Grade 3/4 nausea/vomiting did not occur. The median survival of all patients was 30 weeks, that of those who responded was 48 weeks and that of those showing NC or PD was 24 weeks. CONCLUSIONS: This modified FAP regimen was considered useful with a moderate response and less severe toxicity, but further investigation is necessary.

Adult↗
PubMed1998

Preoperative radiotherapy for cancer of the extrahepatic bile duct.

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.

Aged↗
PubMed1998

Surveillance study for clinical stage I testicular seminomas and nonseminomatous germ cell tumors.

BACKGROUND: Optimal therapy for stage I testicular tumors is still controversial. This study evaluated the efficacy of a surveillance policy for patients with testicular stage I seminomas and nonseminomatous germ cell tumors (NSGCT). METHODS: From 1984 to 1996, 24 patients with stage I seminoma and 20 with stage INSGCT were followed after radical orchiectomy with tumor markers and imaging studies. All patients were followed for at least 2 years except for those who recurred within 2 years. Recurrent patients were treated with cisplatin-based chemotherapy. RESULTS: The median follow-up periods for seminoma and NSGCT patients were 41 and 54 months, respectively. Recurrences were detected in 2 seminoma (8.3%) and 10 NSGCT (50%) patients. Eleven of the 12 recurrent patients (92%) were detected within 2 years after orchiectomy. The seminoma patients both recurred in the retroperitoneal lymph nodes, while 70% of the NSGCT patients recurred in the lung and/or retroperitoneal lymph nodes. The recurrent seminoma patients were treated with chemotherapy and are alive without disease for 1 7 and 24 months afterorchiectomy. One NSGCT patient died of cancer, but the other 9 recurrent NSGCT patients are alive without disease at 25 to 113 months after orchiectomy. CONCLUSIONS: Surveillance alone is reliable for monitoring patients with stage I testicular seminoma and NSGCT. The majority of recurrences occurred within 2 years, necessitating intensive follow-up for 3 years. As the lung metastatic rates in NSGCT patients were high, a more accurate assessment for lung metastasis is desirable in these patients.

Adolescent↗
PubMed1998

Characteristics of vitamin D3 receptor (VDR) binding to the vitamin D response element (VDRE) in rat bone sialoprotein gene promoter.

Bone sialoprotein (BSP) is a mineralised tissue-specific protein that is highly expressed during the initial formation of bone and cementum. Expression of BSP is suppressed by the osteotropic hormone, 1,25-dihydroxyvitamin D3 (vitamin D3), which regulates bone remodelling. In previous studies, we have identified a vitamin D response element (VDRE) that is integrated with a novel inverted TATA box in the rat BSP promoter which mediates the suppression of BSP transcription (1). Although the nucleotide sequences of VDREs in different genes conform to a direct (hexamer) repeat, spaced by three nucleotides, the precise sequences are unique for each VDRE. To determine whether the nucleotide differences in the VDRE influence VDR binding, we have compared interactions of VDR proteins with various VDREs using gel mobility shift analysis. Both natural and recombinant VDRs bound to rat BSP and both mouse and porcine osteopontin (OPN) VDRE oligonucleotides in a concentration-dependent manner with a strong preference for dimer formation, whereas equal amounts of dimer and monomer were bound to the human osteocalcin VDRE. However, whereas a truncated VDR comprising the DNA binding domain alone bound the mouse osteopontin VDRE, it failed to interact with the porcine OPN and rat BSP VDREs. VDR binding to the BSP was sequence specific, as shown by mutagenesis analysis, and could be abolished by heat and VDR antibody. These studies demonstrate that subtle differences in the nucleotide sequence of VDREs affect VDR binding, which mediates the vitamin D3 response.

Animals↗
PubMed1998

A psychobehavioral factor, alexithymia, is related to coronary spasm.

The aim of this study was to assess whether the psychobehavioral pattern alexithymia is related to coronary artery spasm. Alexithymia, deficient psychological awareness, was examined using the Minnesota Multiphasic Personality Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine provocation, and in 109 patients with chest pain syndrome who were shown to have almost normal coronaries without inducible coronary spasm on coronary angiogram (control group). Alexithymia was approximately twice as prevalent in the coronary spasm group (31%) as in the control group (14%) (p<0.01). Among various conventional risk factors including hyperlipidemia, obesity, diabetes mellitus, hypertension, hyperuricemia, or family history of ischemic heart disease, only male sex and smoking were more prevalent in the coronary spasm group than in the control group (p<0.001). The odds ratios of coronary spasm adjusted for all the other risk parameters including sex and age were 4.14 [95% confidence interval (CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A psychobehavioral pattern, alexithymia, relates to coronary spasm. This relationship is independent of the conventional coronary risk factors.

Adult↗
PubMed1998

Comparison of thrombolytic therapies with mutant tPA (lanoteplase/SUN9216) and recombinant tPA (alteplase) for acute myocardial infarction.

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.

Aged↗
PubMed1998

Metastatic model of human colon cancer constructed using orthotopic implantation in nude mice.

Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors, but these tumors rarely metastasize. This is a problem for studies into the biological behavior of metastatic subpopulations of human colorectal cancers. We have followed the evolution of the parental line and of a variant of human colon carcinoma KM12 cells, that were both tumorigenic, following implantation into the s.c. or cecal wall of nude mice. The tumors growing s.c. did not produce visceral metastases, whereas the cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. However, the incidence of liver metastases was different between the parental cell line KM12C cells and the in vivo selected cell line KM12SM cells after orthotopic inoculation. The morphological findings of KM12 cells proliferating in a monolayered sheet revealed that these two cell lines consisted of various cell populations. These results suggest that in the orthotopic colon cancer models, liver metastasis is defined by difference in subpopulations of metastatic phenotypes to the liver with early dominance of its growth in the implanted organ. As a result, our new model using orthotopic implantation of KM12SM cells, which produce a 50% incidence of liver metastasis, can help to provide a technique to study the biological behavior of metastatic subpopulations of human colon cancers.

Animals↗
PubMed1998

Oxygen carrying capacity and oxygen supply rate of artificial oxygen carrier, Neo Red Cell (NRC).

Neo Red Cell (NRC), which is the liposome encapsulated hemolysate, has been developed as an artificial oxygen carrier. Oxygen carrying capacity and oxygen supply rate of NRC were estimated by continuous measurement of dissolved oxygen concentration in a spinner vessel. Oxygen carrying capacity of the medium was risen by adding NRC. The oxygen supply rate of the NRC medium containing hepatocytes was determined by the oxygen consumption rate of hepatocytes. The addition of NRC gave no effect on the oxygen transfer rate from gas phase to liquid phase (or kL a value) of the solution in the spinner vessel. The rate of oxygen absorption to NRC was limited by the oxygen transfer rate from gas phase to liquid phase in the spinner vessel. These results indicate that the oxygen supply from NRC may sustain the high-density culture of mammalian cells.

Air↗
PubMed1998

Assessment of the oxygen transport capacity of NRCs with a 70% blood exchange in rats.

Neo red cells (NRCs) are a blood substitute representing stroma free hemolysate (SFHL) encapsulated in liposomes and containing NAD, glucose, adenine, and inosine, etc. as substrates or coenzymes of the Embden-Meyerhof pathway in RBCs and inositol hexaphosphate (IHP) as an allosteric effector. The oxygen transport efficiency (OTE) of NRCs was increased to > 45% when the oxygen partial pressure in arterial blood increased. We carried out exchange transfusion with NRCs in rats, monitored their functioning as a blood substitute in vivo, and demonstrated that NRCs worked sufficiently. First, we confirmed that the OTE of NRCs was augmented by increasing the oxygen supply to the rats by using oxygen masks. Second, we carried out 70% blood exchange with NRCs (with hemoglobin concentrations of 4, 5, 6, or 7 g/dl), and compared these experimental groups with control groups (RBC and saline). Each sample was contained bovine albumin (final volume of 5% (w/v)). As a result, the NRC groups with hemoglobin concentrations of 5, 6, and 7 g/dl showed stability after the exchange transfusion. On the other hand, the NRC group with hemoglobin concentration of 4 g/dl and the saline group showed respiratory acidosis and a drop of blood pressure and heart rate, and thus did not maintain an adequate oxygen supply. We concluded that a hemoglobin concentration of > 5 g/dl was sufficient in the NRC solution, and demonstrated in an experiment on animals that the OTE of NRCs was increased by using oxygen masks.

Administration, Inhalation↗
PubMed1998

The reduction of methemoglobin in Neo Red Cell.

The hemoglobin oxidation factors that produce methemoglobin (metHb) were studied, for example, loss of enzymatic activity, lack of electron carrier and effect of lipids. The adverse effect of lipids is very pronounced and must be eliminated as much as possible in the producing Neo Red Cell (NRC). The process of swelling was studied. Liquid for swelling was varied from water to basic liquids. The pH of swollen lipids varied from acidic to neutral or basic, metHb was decreased and the enzymes in the Embden-Meyerhof pathway were activated. Phosphatidylcholine (PC) which is a component of mixed lipids is decomposed to lisophosphatidylcholine (liso-PC) in basic pH liquids, but liso-PC formation was not detected when the pH of swollen lipids was under 7.8. For both metHb formation and PC decomposition, swelling with the same quantity of 0.2 N aqueous sodium hydroxide proved optimal.

Blood Substitutes↗
PubMed1998

Alteration of the CDKN2A gene in pancreatic cancers: Is it a late event in the progression of pancreatic cancer?

Various genetic changes are involved in progression of various cancers. We examined alterations (deletion, sequence abnormalities, methylation) of the CDKN2A gene in cell lines and tumor tissues of pancreatic cancers. Some alterations of this gene were found in all the 12 cell lines examined. In the primary lesions of pancreatic cancers, homozygous or hemizygous deletion were found in 8 of 24 ductal carcinoma and 4 of 9 other types of carcinomas. It appears that there is an association between the alteration of this gene and tumor size, regional lymph node metastasis and hematogenous distant metastasis in the ductal carcinoma, but not in the other types of carcinomas. All the 5 liver metastatic lesions of the ductal carcinoma examined revealed homozygous or hemizygous deletion and 3 bp deletion. These results suggest that inactivation of the CDKN2A gene occurs more frequently in cell lines than in pancreatic cancer tissues. Such genetic events on the CDKN2A gene may play an important role possibly at a later step in the progression of pancreatic ductal carcinoma.

Adult↗
PubMed1998

[Long-term results of mitral valve repair with artificial chordae tendineae].

The long-term results of mitral valve repair using artificial polytetrafluorethylene (PTFE) chordae were assessed in 61 consecutive patients with pure mitral regurgitation who underwent mitral valve repair with replacement of elongated or ruptured chordae tendineae between 1992 and 1996. There were 36 men and 25 women aged from 14 to 73 years (mean 52.1 +/- 13.8 years). The patients were followed up for between 1 to 73 months (mean 29.3 +/- 17.6 months). Fifty-five patients underwent mitral valve repair of the anterior leaflet and 6 repair of the posterior leaflet. There were two hospital and two late deaths. Actual survival rate at 5 years was 93.1%. Freedom from cardiac events at 5 years was 87.8%. Two patients required reoperation due to hemolysis. There were three occurrences of non-fatal thromboembolism. Although further investigation is necessary in a large population, expanded PTFE sutures are excellent for chordal replacement during mitral valve repair.

Adolescent↗
PubMed1998

Dose-related vestibular and cochlear effects of transtympanic gentamicin.

HYPOTHESIS: To test the relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected gentamicin in the Mongolian gerbil. BACKGROUND: Transtympanic gentamicin is gaining favor as a relatively noninvasive treatment for Meniere's disease (MD). Few basic science studies exist regarding the vestibular and cochlear toxicities and dosage and administration schedules, however. The absence of standardized procedures and use of different species as animal models may account for the variable outcomes and lack of agreement found in the literature. METHODS: Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1x) and five (5x) daily injections of gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected controls. RESULTS: Two weeks after injection, qualitative and quantitative changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin injected groups. Statistically significant decreases in hair cells were seen when 5x injected ears were compared with 1x injected ears and when 1x injected ears were compared with control ears. When damage was observed in the posterior crista sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS: Our results suggest that in the gerbil, gentamicin is ototoxic but not selectively vestibulotoxic. In general, increasing the number of transtympanic injections increases the damage to sensory hair cells in both the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in both cochlear and vestibular hair cells from the same animal.

Animals↗
PubMed1998

[Serial changes in mitral regurgitation after mitral valve repair with artificial chordae tendineae: assessment by transesophageal echocardiography].

Serial changes in mitral regurgitation after anterior mitral valve repair were examined by transesophageal echocardiography (TEE) in 34 of 86 consecutive patients with pure mitral regurgitation who underwent anterior mitral valve repair from 1987 to 1996. The patients were divided into two groups: 15 patients undergoing mitral repair with polytetrafluoroethylene (PTFE; PTFE group) and 19 undergoing conventional mitral repair without PTFE (non-PTFE group). The PTFE group included 11 men and 4 women with a mean age of 52.1 years. They were followed for mean 22.8 +/- 12.0 months. The non-PTFE group included 12 men and 7 women with a mean age of 53.9 years. They were followed for mean 33.9 +/- 20.4 months. Mitral regurgitation jet areas were observed at the time of operation, 1 month after mitral valve repair, and in the late follow-up period. Regurgitation jet areas were 0.7 +/- 0.7, 1.1 +/- 0.9 and 2.5 +/- 2.1 cm2 in the PTFE group, and 1.1 +/- 1.3, 2.4 +/- 1.7, 4.7 +/- 2.9 cm2 in the non-PTFE group. The jet area was significantly smaller in the PTFE group than in the non-PTFE group at 1 month after operation and in the late follow-up period. Moderate to severe regurgitation was observed in two patients (13.3%) in the PTFE group, and eight patients (42.1%) in the non-PTFE group. Mitral valve repair with PTFE showed better results than conventional mitral valve repair without PTFE during the mean follow-up period of 23 months.

Adult↗
PubMed1998

[Automated cardiac output measurement by color Doppler echocardiography].

Recently, automated cardiac flow measurement (ACM) has been developed for measuring the volume flow rate of blood flow through the left ventricular outflow tract. Measurements of left ventricular cardiac output by the ACM method were compared with those by the thermal dilution method with a Swan-Ganz catheter in 27 patients (16 men and 11 women; aged 44 +/- 3 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The total time required for left ventricular stroke volume calculation by both ACM and pulsed Doppler methods was measured in 10 patients (six men and four women; aged 41 +/- 2 years). There was an excellent correlation in the measurements of cardiac output between the ACM and thermal dilution methods (y = 0.77x + 0.77, r = 0.84, SEE = 0.4 l/min). The total time required for left ventricular stroke volume calculation by the ACM method was significantly shorter than that by the pulsed Doppler method (92 +/- 10 vs 177 +/- 30 sec, p < 0.01). The ACM method is simple, quick, and accurate for the automated assessment of cardiac output.

Adult↗
PubMed1998

[Assessment of coronary flow reserve in patients with hypertrophic cardiomyopathy using transthoracic color Doppler echocardiography].

Abnormal coronary flow pattern and coronary vasodilator reserve have been identified in patients with hypertrophic cardiomyopathy (HCM) using invasive techniques. The characteristics of coronary flow velocity and coronary flow reserve were evaluated by noninvasive-recording of coronary flow velocity in the distal portion of the left anterior descending coronary artery in 7 patients with HCM and 7 normal subjects using transthoracic color Doppler echocardiography. Coronary flow velocity was measured at rest and during intravenous infusion of adenosine triphosphate (0.15 mg/kg/min). Diastolic peak velocity, diastolic mean velocity, the time from the beginning of diastole to peak velocity (TVP) and velocity half time from peak velocity was measured in each group. Coronary flow reserve was obtained as the ratio of hyperemic mean velocity to resting mean velocity. TVP was significantly prolonged in the patients with HCM compared with the normal subjects (159 +/- 38 vs 103 +/- 54 msec, p < 0.05). Velocity half time was significantly shorter in the patients with HCM compared with the normal subjects (304 +/- 138 vs 451 +/- 109 msec, p < 0.05). Although diastolic mean velocity during hyperemia was not different between the 2 groups (62 +/- 8 vs 70 +/- 19 cm/sec), diastolic mean velocity at rest was significantly higher in the patients with HCM than in the normal subjects (39 +/- 6 vs 26 +/- 7 cm/sec, p < 0.01). Therefore, coronary flow reserve was significantly lower in the patients with HCM than in the normal subjects (1.6 +/- 0.4 vs 2.7 +/- 0.4, p < 0.001). There was a good correlation between diastolic mean velocity and the ratio of interventricular septal to posterior left ventricular wall thickness (y = 0.024x + 0.46, r = 0.75). Transthoracic assessment of coronary flow velocity using color Doppler echocardiography reveals that coronary flow reserve is reduced in patients with HCM because of increased baseline resting diastolic mean velocity.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Heat shock-induced excessive relaxation of DNA in Escherichia coli mutants lacking the histone-like protein HU.

Plasmid DNA in exponentially growing Escherichia coli immediately relaxes after heat shock but the relaxed DNA re-supercoils rapidly, the despite continued presence of the heat shock conditions. We have now obtained genetic evidence indicating that the histone-like protein HU of E. coli is required for this re-supercoiling of DNA. Plasmid DNA in a hupA-hupB double gene-disruption mutant relaxed excessively after heat shock, while the relaxation of DNA in a himA-himD double gene-disruption mutant and in an hns insertion mutant was transient, thereby indicating that HU protein, but not IHF or H-NS proteins, is required for the re-supercoiling of DNA. Exposure of the hupA-hupB double mutant to a temperature of 50 degrees C led to both excessive relaxation of DNA and to a decrease in viable cell number but temperatures lower than 46 degrees C did not lead to these events. Based on these results, we propose that HU protein maintains the negative supercoiling of DNA during thermal stress and contributes to cellular thermotolerance in E. coli.

Bacterial Proteins↗