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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 595 records · Page 33Linked to original sources

[Pharmacokinetics and clinical efficacy of flomoxef in neonates].

Clinical pharmacology and efficacy of flomoxef (FMOX) in neonates were investigated. And the following results were obtained. 1. Mean serum concentrations of FMOX at 30 minutes after administration were 24.3 micrograms/ml, 47.6 micrograms/ml, and 85.8 micrograms/ml at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg administered, respectively. 2. Mean serum half-lives of FMOX were 3.4 hours in 0-3 day-old neonates, and 2.6 hours in 4 day-old or older subjects. 3. A dose response was evident among different dose groups given 10 mg/kg, 20 mg/kg, and 40 mg/kg. 4. Urinary recovery rates of FMOX in the first 6 hours after administration ranged between 12.8 and 51.1%. 5. FMOX was effective in 7 out of 8 cases in which causative pathogens were identified. 6. Diarrhea was observed in 1 case as a side effect of the drug, but the symptom was relieved soon after the completion of the treatment. There was no case in which any abnormal laboratory results were observed. 7. FMOX has a broad spectrum of activities against Gram-positive and Gram-negative aerobes and anaerobes. It is stable against most of beta-lactamases. It was demonstrated to be highly effective in our study, and yet without any serious side effects. FMOX is therefore considered to be one of the useful agents of the first choice for the treatment of bacterial infections such as sepsis and urinary tract infections in neonates and infants.

Age Factors↗

Inhibition of in vitro DNA chain elongation of 5-trifluoromethyl-2'-deoxyuridine residue in the template.

5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd) is incorporated into the DNA of mammalian cells in culture. We have synthesized oligonucleotides that allows site specific introduction of CF3dUrd residue into synthetic DNA oligonucleotide. We described here the utilization of these oligonucleotides as template for in vitro DNA synthesis. When CF3dUrd residue located at an internucleotide site in the template, the chain elongation was partially arrested one nucleotide after or before the CF3dUrd residue of template using Escherichia coli polymerase I (Klenow fragment) or human polymerase alpha (pol alpha). These results suggested that a mechanism of antitumor activity of CF3dUrd is inhibition of DNA replication.

Base Sequence↗

Serum concentration and immunohistochemical localization of SPan-1 antigen in pancreatic cancer. A comparison with CA19-9 antigen.

We studied SPan-1 antigen in 64 patients with pancreatic cancer by measuring serum concentrations with RIABEAD and examining the intratumor staining patterns immunohistochemically. Serum concentrations were elevated (greater than 30 U/ml) in 46 patients (72.0%), roughly the same percentage as with elevated serum CA19-9 concentrations. Ten out of 19 patients without CA19-9 antigen expressed SPan-1, and the combined rate of positivity was 86% (55/64). Immunohistochemically, CA19-9 was localized to the apical surface and the supranuclear cytoplasm of normal epithelial cells, but SPan-1 was localized to the supranuclear cytoplasm or throughout the cytoplasm. After malignant degeneration, both antigens were found over the entire plasma membrane, throughout the cytoplasm (loss of polar distribution) and in the stroma surrounding the cells. SPan-1 was detected in 48 out of 54 adeno-carcinomas of the pancreas (89%), and all cases with an elevated serum concentration displayed stromal staining in the cancer tissues. The utility of SPan-1 antigen as a tumor marker for diagnosing pancreatic cancer was found to be equal to that of CA19-9.

Adenocarcinoma↗

[Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer].

The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate.

Breast Neoplasms↗

[Combination chemotherapy with orally administered UFT and leucovorin (LV)].

We evaluated the efficacy of the combination therapy of UFT with Leucovorin (LV) against mouse colon adenocarcinomas and human colon adenocarcinoma. In vitro studies, it was shown that LV potentiated the cytotoxicity of FUra against 7 out of 9 cell lines used in this experiment. In vivo studies, the antitumor activity of UFT against mice bearing colon 38 adenocarcinoma was increased following administration of LV either before, after or at the time of treatment with UFT. Further studies were performed on the combination effect of UFT and LV against mouse colon 26 adenocarcinoma and human colon adenocarcinoma KM20C. Consequently, the combined treatment of UFT with LV was more effective than UFT alone against two cell lines. Our studies suggest that combination chemotherapy of UFT with LV is a promising approach for the treatment of a human colon cancer in clinical practice.

Adenocarcinoma↗

[Hemodynamic effects of endothelin in anesthetized dogs].

The purpose of the present study was to investigate and compare the hemodynamic responses that can be elicited in anesthetized dogs by intravenous administration of endothelin at rates of 300 (group E-I, n = 9) and 600 pmol.kg-1 (group E-II, n = 9) for 15 minutes. In group E-I, no significant pressure response was observed after administration of endothelin and cardiac index remained unchanged throughout the experiment. However, right and left ventricular work indices increased significantly but left ventricular maximum dp/dt and pulmonary vascular resistance decreased significantly. In group E-II, mean arterial pressure increased significantly by elevating systemic vascular resistance with marked decrease in cardiac index. However, right and left ventricular work indices remained unchanged throughout the experiment. On the other hand, each dose of endothelin significantly increased pulmonary capillary wedge pressure and left ventricular end-diastolic pressure but decreased heart rate. The present data revealed that the hemodynamic effects were different according to the doses of endothelin infused. In conclusion, our results show that endothelin (600 pmol.kg-1 BW) produces a long lasting increase in arterial pressure and endothelin-induced pressure responses are caused by an elevation in systemic vascular resistance.

Anesthesia, General↗

[Effects of buserelin presurgical treatment on vascularity in the sub-serosal interstitial tissue of the uterus and operative blood loss at hysterectomy in women with uterine leiomyoma and adenomyosis].

We examined 194 cases of uterine leiomyoma and adenomyosis who received total abdominal hysterectomy, in order to compare the effect of presurgical medical treatment such as with Buserelin, Danazol and Pill, on operative blood loss with non-treated group. The operative blood loss was 314.0 +/- 177.2 ml (mean +/- SD) in the control group (n = 145), 211.2 +/- 64.1 ml in the Buserelin-treated group (n = 26), 276.8 +/- 110.7 ml in the Danazol-treated group (n = 10), and 396.6 +/- 213.1 ml in the Pill-treated group (n = 13). The operative blood loss in the Buserelin-treated group was significantly lower than in the control group (p less than 0.01) and in the Pill-treated group (p less than 0.05). After considering the pathology of the uterus, the uterine size, and the level of expertise of the surgeon, the operative blood loss in the Buserelin-treated group was significantly lower than in the control group. We measured the capillary space, small arteries and veins in the sub-serosal interstitial tissue of the uterus, and observed that the vascular space decreased significantly (p less than 0.01) in the Buserelin-treated group compared to the control group. From these facts it may be concluded that Buserelin presurgical treatment reduces the operative blood loss at hysterectomy, and it seems very likely that the decrease in vascularity may play an important role.

Blood Loss, Surgical↗

[A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs].

Plasma catecholamines, plasma renin activity, plasma aldosterone and plasma cortisol during hypotension induced by sodium nitroprusside and nicardipine were studied in 27 mongrel dogs under 0.87% halothane in oxygen. They were randomly divided into three groups: sodium nitroprusside (group S: n = 8), nicardipine (group N: n = 8) and controls (group C: n = 9). Group C received no vasodilator therapy and served as a control. Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes in hypotensive groups. No changes were noted in plasma catecholamines and plasma cortisol in group C throughout the experiment, but plasma renin activity and plasma aldosterone decreased progressively. During hypotension induced by sodium nitroprusside and nicardipine, plasma epinephrine was significantly higher than the control value. However, after the hypotensive drugs were discontinued, plasma epinephrine decreased slightly. During and after induced hypotension, plasma renin activity of group N and group S were significantly higher than the control values. The highest levels of plasma renin activity 36.7 ng.ml-1.hr-1 in group N and 23.2 ng.ml-1.hr-1 in group S were observed. Plasma aldosterone concentration was significantly higher than the control value in group N. The maximum increase occurred 30 minutes after discontinuation of the nicardipine and the highest concentration of plasma aldosterone was three times control value. In contrast, in group S, plasma aldosterone was unchanged from the control value. Plasma cortisol concentration of group N was significantly increased than the control value. However, in group S, plasma cortisol concentration showed a slight but not significant increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

[Effects of diaphragm plication for phrenic nerve paralysis on respiratory mechanics and diaphragm function].

The purpose of this study is to examine the effects of unilateral diaphragm plication for phrenic nerve paralysis on the respiratory mechanics and diaphragm function. Study 1: We performed thoracotomy (BASELINE), left phrenicotomy (INJURY) and left diaphragm plication (PLICATION) in ten dogs. After chest was closed in each condition, measured were the tidal volume (TV), respiratory rate (f), esophageal and gastric pressure swing (delta Pes, delta Pga), dynamic compliance (Cdyn) the ratio of gastric to esophageal pressure swing (delta Pga/delta Pes) and the work of breathing per liter (WOB/L) under stable spontaneous breathing. Study 2: In eight other left-phrenicotomized dogs, Pdi and fractional shortening of the costal diaphragm during contralateral electrophrenic stimulation were measured before and after plication. After plication TV, delta Pga/delta Pes, Cdyn, Pdi and fractional shortening during stimulation increased significantly, whereas Pes and WOB/L decreased significantly compared with INJURY condition. In conclusion unilateral diaphragm plication after paralysis improves the intact hemidiaphragm contractility and diaphragmatic contribution to breathing.

Animals↗

[Studies on right ventricular performance in surgical treatment for primary lung cancer--especially in changes of right ventricular ejection fraction in acute phase].

In surgical treatment for lung cancer, increase of right ventricular afterload associated with decrease of pulmonary vascular bed after lung resection is serious problem in acute phase. Intensive care is necessary for the patients having major surgery, especially in aged. Until now, we have studied on pre and post operative extravascular lung water (EVLW) in addition to measurement of conventional hemodynamic changes on right ventricular afterload. And then, we have discussed when we should start to care intensively for degradation of compensatory hyperdynamic change. According to percent exchanges (delta %) between pre and post operative measurement, we established following criterion 1) delta %HR greater than 150% 2) delta SVI less than 60% 3) delta % PARI greater than 200% 4) observed postoperative EVLW greater than predicted postoperative EVLW. Furthermore, we investigated the correlation with these criterion and RVEF in 14 patients using a rapid computerized thermodilution method on right cardiac function in acute phase. We found that 1) changes of RVEF seem to depend on endsystolic volume 2) RVEF decreased just after operation and then slowly increased until 48 hours 3) PARI elevated to 194 +/- 117% in average at 6 to 24 hours showing significant inversed linear correlation to changes of RVEF (R = -0.54). The patients having prolonged elevation of PARI showed degradation of cardiac output and RVEF. RVSWI showed compensative acceleration gradually with increased right ventricular afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Duodenal varices treated successfully by percutaneous transhepatic obliteration: report of a case].

A 73-year-old female with bleeding from duodenal varices treated by percutaneous transhepatic obliteration (PTO) was reported. She was admitted to our hospital because of tarry stool and general malaise. Gastroduodenoscopy revealed tortous elevations in the descending part of the duodenum, and observed intermittent bleeding. Percutaneous transhepatic portography (PTP) was carried out. PTP revealed duodenal varices supplied via the inferior pancreaticoduodenal vein and drained to the inferior vena cava, and continuously obliterated by gelfoam. Duodenal varices disappeared after obliteration and we observed no recurrence of varices for a year endoscopically. In general, it is accepted that the causes of the upper gastrointestinal bleeding secondary to portal hypertension are esophagogastric varices, hemorrhagic gastritis, gastro-duodenal ulcer, and so on. However, we must keep in mind the case with duodenal varices in which bleedings are of unknown origin. We also reviewed duodenal varices reported in Japanese literature from 1968 to 1989.

Aged↗

Expression and secretion of goat alpha-lactalbumin as an active protein in Saccharomyces cerevisiae.

An expression plasmid for goat alpha-lactalbumin in Saccharomyces cerevisiae, pSKA100, was constructed into a shuttle vector, pYG100, by inserting cDNA which encodes goat pre-alpha-lactalbumin and two-thirds of the 3'-non-coding region. The goat alpha-lactalbumin was expressed under the yeast glyceraldehyde 3-phosphate dehydrogenase (GPD) promoter and terminator of pYG100 and secreted in the growth medium for yeast as a precise mature protein, possessing specific activity essentially the same as that of authentic goat alpha-lactalbumin in lactose synthesis.

Amino Acid Sequence↗

[Oral etoposide therapy in stage III-IV ovarian carcinoma].

Seven patients with Stage III-IV ovarian carcinoma were treated with oral etoposide. The patients received a dose of 25 or 50 mg/day/body for every day or 21 consecutive days every one months. Four patients received this treatment as second line chemotherapy, two as initial chemotherapy and one as maintenance chemotherapy. One of 6 patients with measurable tumor had complete response, one had partial response and four had no changes. One patient with embryonal carcinoma, who received this treatment as maintenance chemotherapy is in no relapse for 2 years and 2 months. Leucopenia with a WBC under 3,000/mm3 was seen in 3 cases. Oral mucositis occurred in 2 cases, hair loss and gastrointestinal toxicities in 1 case. This method of oral administration is effective, tolerated and convenient for advanced ovarian carcinoma and recurrence following prior, vigorous chemotherapy in a outpatient clinic.

Administration, Oral↗

Protective effects of ONO-3307, a new synthetic protease inhibitor against experimental disseminated intravascular coagulation in rats.

The effects of ONO-3307 (4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with ONO-3307 at a dose of 1, 10 or 100 micrograms/kg/h into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 10 or 100 micrograms/kg/h of ONO-3307 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. Therefore, ONO-3307 inhibited the aggravation of endotoxin-induced experimental DIC in rats.

Animals↗

Structural studies of the contractile tail sheath protein of bacteriophage T4. 1. Conformational change of the tail sheath upon contraction as probed by differential chemical modification.

Differential chemical modifications of tyrosine residues of the tail sheath protein, gp18, were performed to elucidate the structural change of the tail sheath upon contraction. Tyrosine residues of monomeric gp18, extended tail sheath, and contracted tail sheath were nitrated by tetranitromethane, and the modified tyrosine residues in each state of the sheath protein were identified by peptide mapping and amino acid sequence analyses of the isolated peptides. Of 31 tyrosine residues in gp18 monomer or in the extended sheath, 12 or 13 residues (Tyr63 and/or -73, -225, -254, -270, -304, -455, -460, -493, -532, -535, -569, and -590) were modified. When photo-CIDNP difference spectra were measured with monomeric gp18, two peaks, which are due to highly exposed tyrosine residues on the molecular surface of gp18, were observed. These two peaks disappeared when the monomeric gp18 was nitrated. With contracted sheath, however, only eight tyrosine residues (Tyr225, -254, -270, -455, -460, -493, -532, and -535) were nitrated on the contracted sheath. Chemical modification of cysteine residues by sulfhydryl group specific reagent ABD-F [(4-aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole] revealed that, among five cysteine residues, Cys377, Cys477, and Cys607 have a sulfhydryl group. Cys402 and Cys406 were modified only under reducing conditions, which strongly suggested the presence of a disulfide bond between these two residues.

Chemical Phenomena↗