Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 307 records · Page 17Linked to original sources

PubMed1990

A new prostaglandin E1 analogue (TFC-612) improves the reduction in motor nerve conduction velocity in spontaneously diabetic GK (Goto-Kakizaki) rats.

A new prostaglandin E1 analogue, TFC-612, was given orally to 2 month-old spontaneously diabetic GK (Goto-Kakizaki) rats for 3 months to ascertain its effects on reduced motor nerve conduction velocity (MCV). A high dose of this compound (0.3 mg/kg body weight) significantly restored MCV after 2 and 3 months of administration, although the low dose (0.03 mg/kg body weight) did not. In addition, 1 month administration of TFC-612 significantly improved the reduced MCV in aged (5 month-old) GK rats only in the high dose group (0.3 mg/kg body weight), but not in the low dose group (0.03 mg/kg body weight). Although TFC-612 significantly suppressed sorbitol accumulation in the sciatic nerves of GK rats in a dose dependent manner after 3 months administration, this suppression was not observed after either 2 months administration to 2 month-old GK rats or after 1 month administration to 5 month-old GK rats. Fasting blood glucose levels of all GK rats remained high throughout the experiments, regardless of TFC-612 administration. TFC-612's improvement on reduced motor nerve conduction velocity was related partly to suppression of sorbitol accumulation, but other factors, including microcirculation, may contribute significantly to this effect. These results suggest that TFC-612 may be beneficial in the treatment of diabetic nerve impairment.

Aging↗

PubMed1990

cis-diamminedichloroplatinum(II)-induced sister-chromatid exchanges and chromosome aberration formation in cultured human lymphocytes and their inhibition by sodium thiosulfate.

cis-Diamminedichloroplatinum(II) (cis-DDP)-induced sister-chromatid exchanges (SCEs) and chromosome aberration formation were studied in human lymphocytes. The mitotic index decreased abruptly at 2 X 10(-6) M cis-DDP and the frequency of SCEs was dose-related; a marked increase was recorded at 10(-6) M cis-DDP. A dose-dependent effect was also found for chromosome aberration formation at concentrations between 10(-11) and 4 X 10(-6) M. The aberrations observed were primarily chromatid breaks and gaps. We also examined the inhibition of these genotoxicities by treating the cells with sodium thiosulfate (STS). Simultaneous treatment with 10(-4)-10(-3) M STS (100-1000-fold molar ratio to cis-DDP) significantly reduced the frequency of SCEs induced by 10(-6) M cis-DDP. Furthermore, a 3-h delay in treating with STS significantly reduced cis-DDP-induced SCEs, but not chromosome aberration formation.

Antioxidants↗

PubMed1990

Response of thermoresponsive neurons of rat's hypothalamus during intracarotid infusion of prostaglandin E2.

We investigated the effect of intracarotid infusion of prostaglandin E2 (PGE2) on the single-unit activity of neurons in the preoptic and anterior hypothalamic (PO/AH) region. A total of 35 neurons in the PO/AH region were examined: 10 were warm-responsive neurons, 6 were cold-responsive neurons, and 19 were thermally insensitive neurons. In the warm-responsive neurons, the activities of 4 neurons were facilitated, while 3 neurons were inhibited and 3 neurons were not affected after intracarotid infusion of PGE2. In the cold-responsive neurons, the activities of 2 neurons were facilitated and 4 neurons were not affected by PGE2 infusion. Furthermore, 15 out of 19 thermally insensitive neurons were not affected by PGE2 infusion. These results suggest that thermoresponsive neurons of the PO/AH region respond well to intracarotid infusion of PGE2, compared with thermally insensitive neurons. However, the direction of neuronal response induced by intracarotid infusion of PGE2 could not be generally categorized based on the thermoresponsiveness of individual neurons.

Action Potentials↗

PubMed1990

Characterization of thrombin- and plasmin-resistant mutants of recombinant human single chain urokinase-type plasminogen activator.

Recombinant human single-chain urokinase-type plasminogen activator (suc-PA) (SM0: wild type) and its variants resistant to plasmin and/or thrombin (SM1: Lys135 to Gln; SM3: Phe157 to Asp; and SM4: Lys135 to Gln and Phe157 to Asp) have been constructed by site-directed mutagenesis with the aim of producing more efficient thrombolytic agents [Miyake, T. et al. (1988) J. Biochem. 104, 643-647]. In the present study, we characterized the recombinant variant scu-PAs expressed in Escherichia coli. They appeared to have structural integrity because their heat-stabilities, immunological reactivities, and circular dichroism spectra were essentially identical to those of each other and of native scu-PA (nscu-PA). In the presence of thrombin, SM3 and SM4 showed efficient clot lysis by all of the assays used, compared with SM0, SM1, and nscu-PA. While in the absence of thrombin, when measured by a fibrin plate method in a purified system, SM3 and SM4 had lower specific activities than SM0, SM1, and nscu-PA, because of their catalytic constants for conversion to the two-chain form (tcu-PA) by plasmin are lower. However, SM4 lysed clots as efficiently as SM0 in plasma by retaining the single-chain form, whereas SM0 was partly converted to the two-chain form.

Autoradiography↗

PubMed1990

A novel model of solitary hepatic tumor in rats using ascites hepatoma AH13: suitability for chemotherapeutic studies.

A highly reproducible model of a solitary hepatic tumor in rats using ascites hepatoma AH13 has been developed using a two-step method which was suitable for quantitative chemotherapeutic studies. Diffuse hepatic metastases were induced first by inoculation of three different ascites hepatomas, AH13, AH130 and AH7974 into the portal vein in a dose-dependent fashion. Second, the induced hepatic tumor (3 x 10(7) cells) was minced into 1 x 1 x 4 mm fragments and implanted in the liver of normal rats. In this procedure, the AH13 strain proved best suited for the generation of a solitary hepatic tumor. The growth of the solitary liver tumor using AH13 was highly reproducible. To demonstrate the suitability of this solitary hepatic tumor model for the evaluation of chemotherapy, the tumor-burdened rats were treated with adriamycin (ADR) and mitomycin C (MMC). The reduction in tumor size was proportional to dosage, and the statistical significance of the differences between the treatment group and control group was proportional to dosage. A synergistic effect of ADR and MMC on the tumor also was demonstrated. This model should prove to be a useful tool for the testing of newly developed treatments of hepatic cancer.

Animals↗

PubMed1990

Leucocytosis induced in rabbits by intravenous or central injection of granulocyte colony stimulating factor.

1. We investigated the effect of intravenous, intracerebroventricular and intrapreoptic injections of human recombinant granulocyte colony stimulating factor (GCSF) on body temperature and acute phase responses in the rabbit, including changes in the plasma concentration of iron, zinc, copper and fibrinogen and in circulating leucocyte count. 2. Neither intravenous nor intracerebroventricular injection of GCSF had any effect on the body temperature. 3. Both the intravenous and the intracerebroventricular injections of GCSF induced a dose-dependent increase in the circulating leucocyte count but neither affected the plasma concentration of iron, zinc, copper and fibrinogen. Furthermore, intrapreoptic injection of GCSF produced leucocytosis but had no effect on the red blood cell count. 4. The present results suggest that GCSF induces leucocytosis through its action on both the peripheral target organs and the central nervous system.

Acute-Phase Reaction↗

PubMed1990

Functional and structural differences in febrile mechanism between rabbits and rats.

1. Febrile responsiveness of rabbits and rats to intravenous (I.V.) or intracerebroventricular injection of human recombinant interleukin-1 alpha (IL-1 alpha), human recombinant interleukin-1 beta (IL-1 beta) and prostaglandin E2 was examined. 2. The I.V. injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.05-2.0 micrograms/kg. A small dose of IL-1 alpha (0.5 micrograms/kg) or IL-1 beta (0.5 micrograms/kg) produced a monophasic patterned fever in both rabbits and rats. A large dose (2.0 micrograms/kg) of IL-1 alpha or IL-1 beta produced a biphasic fever in rabbits, but monophasic fever in rats. Febrile responses in rabbits induced by I.V. injection of IL-1 alpha or IL-1 beta were significantly greater than those in rats induced by these same injections. Furthermore, in both species, the pyrogenicity of I.V. IL-1 beta was greater than that of IL-1 alpha. 3. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.2-20 ng. In rabbits and rats, the ventricular injections of IL-1 alpha and IL-1 beta produced fever with almost the same pattern--monophasic, regardless of injection doses. Although febrile responsiveness of rabbits to ventricular injection of IL-1 alpha was greater than that of rats, responsiveness to IL-1 beta was almost the same in both species. Pyrogenicity of ventricular IL-1 beta was greater than that of IL-1 alpha. However, febrile responses in rats induced by ventricular injections of several doses (2-2000 ng) of prostaglandin E2 were greater than those in rabbits. 4. The present results show that febrile responsiveness of rabbits to I.V. IL-1 is significantly greater than that of rats. However, fever sensitivity within the central nervous system (CNS) of rats is not lower compared with that of rabbits. Therefore, we considered that between the two species there exist structural differences in the organum vasculosum laminae terminalis (OVLT), which is currently believed to be the pathway of pyrogen to the CNS and/or the site of production of pyrogenic prostaglandins. 5. Histological examinations showed that the rabbit's OVLT has two vascular components with capillaries, one in the layer near the third ventricle and the other in the layer near the subarachnoideal space. However, the rat's OVLT only has a single component, in the layer near the subarachnoideal space.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Central action sites of interleukin-1 beta for inducing fever in rabbits.

1. Intravenous (I.V.) human recombinant interleukin-1 beta (IL-1 beta) in high doses caused biphasic fever in rabbits. In lower doses it produced only the first phase of fever. 2. Intracerebroventricular (I.C.V.) or intrapreoptic-anterior hypothalamic (IPOAH) injection of IL-1 beta produced a rather rapid and marked increase in rectal temperature. 3. Subcutaneously administered indomethacin partly reduced the first phase and more substantially the second phase of the biphasic fever induced by high doses of I.V. IL-1 beta. The first phase may thus be prostaglandin independent at least in part. 4. In the fever induced by I.C.V. injection of IL-1 beta, subcutaneous indomethacin reduced the elevation of the rectal temperature considerably and delayed the onset of fever. Administration of indomethacin (I.C.V.) caused marked inhibition of the fever induced by a lower I.C.V. dose of IL-1 beta, but with a high dose the onset of the fever was delayed for about 1 h, without the total rise being affected. 5. It is concluded that the first phase of biphasic fever is caused by IL-1 beta acting via an extravascular component of the organum vasculosum laminae terminalis (OVLT) or the circumventricular organs accessible from only the blood side, to release arachidonate metabolites, presumably prostaglandin E2 (PGE2), and the second phase by IL-1 beta acting via the blood-brain interface accessible both from the blood side and the brain side, to release metabolites other than PGE2.

Animals↗

PubMed1990

Effects of physical training on febrile and acute-phase responses induced in rats by bacterial endotoxin or interleukin-1.

1. We investigated the effect of physical training on febrile and acute-phase responses induced in rats by intravenous (I.V.) injection of bacterial endotoxin or human recombinant interleukin-1 beta (IL-1). Physical training was performed by swimming for 1 h per day, 5 days a week. After four weeks of training, animals were used in the experiments. 2. The I.V. injection of endotoxin produced a febrile response in the trained group but not in the control group. However, there were no statistically significant differences between febrile responses induced by the I.V. injection of IL-1 in the control and trained groups. 3. The I.V. injection of endotoxin significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration in both the control and the trained groups. However, the decreases in the plasma iron and zinc concentrations in the trained group were significantly greater than those in the control group. The I.V. injection of endotoxin increased the circulating leucocyte count in the only trained group. 4. The I.V. injection of IL-1 significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration and the circulating leucocyte count in both the control and the trained groups. However, between the two groups, no significant differences in the values of acute-phase reactants were observed. 5. The present results suggest that the ability to produce cytokine(s) to induce febrile and acute-phase responses is enhanced by physical training. However, physical training has no effect on the febrile and acute-phase responses induced by IL-1.

Acute-Phase Reaction↗

PubMed1990

Myosin heavy chain isoform changes in rat diaphragm are induced by endurance training.

After rats were chronically exercised by endurance swimming, an augmentation of succinic dehydrogenase (SDH) activity in the diaphragm and the EDL muscle was observed. In addition, endurance training induced a decrease in the percentage of myosin heavy chain (MHC) IIb in the diaphragm, and a decrease in the percentage of HCIIb concomitant with an increase in the percentage of HCIId in the EDL muscle. These results indicate that endurance training induced not only an increase of the oxidative capacity but also an alteration in the expression of an MHC phenotype in the diaphragm and skeletal muscle.

Animals↗

PubMed1990

[Urinary excretion of glycine.prolile dipeptidile aminopeptidase, N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase and low molecular protein in patients with renal cell carcinoma].

Urinary excretion of glycine.prolile dipeptidile aminopeptidase (GP-DAP), N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2-M), alpha 1-microglobulin (alpha 1-M) was studied preoperatively in 32 patients with renal cell carcinoma. The excretion indices of GP-DAP, AAP and NAG were significantly higher than those in the healthy control group. The excretion of these enzymes obviously reflected the degree of the tumor progression. However, positive rates were not remarkable (37% for GP-DAP, 37% for AAP and 28% for NAG). The excretion of beta 2-M and alpha 1-M was not increased in renal cell carcinoma patients.

Acetylglucosaminidase↗

PubMed1990

[Clinical evaluation of urinary glycyl-prolyl dipeptidyl aminopeptidase in patients with urological disease].

Urinary glycyl-prolyl dipeptidyl aminopeptidase (GP-DAP) activity was measured in 18 healthy adults and 252 patients with urological diseases. The GP-DAP activity was significantly higher in patients with prostatic cancer, bladder cancer or renal cancer and also in patients with acute prostatitis or pyelonephritis than in healthy adults. GP-DAP activity was also studied during anticancerous chemotherapy and proved to be a sensitive parameter for renal damage as are urinary N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, beta 2-microglobulin, alpha 1-microglobulin, and albumin. The analysis of tissue activities suggested that GP-DAP was located not only in the renal parenchyma but also in the prostate and seminal vesicles.

Acetylglucosaminidase↗

PubMed1990

A case of malignant histiocytosis successfully treated with combination interferon and etoposide therapy.

A 66-year-old woman with malignant histiocytosis was treated with a combination of recombinant gamma interferon (GI-3) and etoposide. Following partial response to intravenous gamma interferon (9 x 10(6) units (U)/day) alone, the patient received an eight-months course of subcutaneous gamma interferon (0.5 x 10(6) U/day) and intravenous etoposide (100 mg/week). After two years, the patient remains in complete remission. The present case report discusses the successful use of combination gamma interferon and etoposide for the treatment of malignant histiocytosis.

Aged↗

PubMed1990

[Inflammatory reaction and laboratory tests: IAP (immunosuppressive acidic protein)].

The immunosuppressive acidic protein (IAP), a type of alpha 1-acid glycoprotein has been used as to monitor cancer and inflammation in patients, though it lacks disease specificity. We studied the serum IAP values in 41 patients with renal cell carcinoma. The normal upper limit of serum IAP concentration is 500 micrograms/ml, and a higher value was determined as positive. Serum IAP values and its positive ratios as determined by Robson stage analysis were respectively, 495 + 118 micrograms/ml and 35% (6/17), 757 + 333 micrograms/ml and 90% (9/10), and 921 + 277 micrograms/ml and 100% (14/14), at low (1 + 2) stage, stage 3, and stage 4, respectively. We also studied serum IAP values of the 41 patients above according to Satomi's classification. The positive ratio as 100% (14/14) for the quick type, and 67% (18/27) for the slow type. In addition, we studied the serial serum IAP values in these patients. The serum IAP values decreased to or were within the normal range by one month after operation in 10 patients with curative nephrectomy, while in 8 patients with non-curative nephrectomy abnormally high levels of serum IAP were seen one month after operation except in one case. The serum IAP value was considered as a useful factor in determining the prognosis of patients with renal cell carcinoma.

Biomarkers, Tumor↗

PubMed1990

[Evaluation of effectiveness of rokitamycin dry syrup in acute enteritis in pediatrics. A comparative study on rokitamycin and fosfomycin dry syrups].

Because Campylobacter jejuni is most frequently identified as a causative organism of bacterial enteritis in pediatrics, a study was done to evaluate the clinical efficacy against Campylobacter enteritis and the safety of a macrolide antibiotic, rokitamycin (RKM). In case of acute enteritis, RKM was used in a form of dry syrup at a dose level of approximately 30 mg (in potency)/kg body weight and its efficacy and safety were compared to those of fosfomycin (FOM) dry syrup which is currently in use at a dose level of 60 mg (in potency)/kg. Both drugs were administered, as a rule, in 3 divided daily dose (RKM before meal and FOM after meal) for 5 consecutive days. Comparisons of the drugs were made using a well-controlled method. Obtained results are summarized as follows. 1. No significant differences in background factors of the 2 drug groups were apparent, hence it was deemed that no obstacles existed in making comparative studies of the 2 groups with regard to their efficacies and safeties. 2. Overall efficacy rate against Campylobacter enteritis was 100% in the RKM group with a rate of excellent efficacy of 91.3% and the former was 94.4% in the FOM group with the latter of 72.2%. Though the RKM group apparently showed higher rates by 5.6% and 19.1%, respectively, for overall and excellent efficacies, they were not statistically significant as both drugs showed good efficacies. When acute cases of enteritis other than those caused by Campylobacter were included in the analysis, overall efficacy rates and rates of excellent efficacy were, respectively, 97.6% and 85.7% for the RKM group and 88.6% and 68.2% for the FOM group, thus RKM showed higher efficacy rates by 9.0% and 17.5%, respectively. These differences were deemed statistically significant using the U-test. 3. Numbers of days required for most of the major symptoms to subside were 3 days or less for the group for which RKM was used against Campylobacter enteritis. Similar results were observed for the FOM group also. In cases of acute enteritis due to other causes than Campylobacter, slower recoveries were observed for both the RKM and the FOM groups than in Campylobacter enteritis cases, with the latter group slower than the former. In cases of puruloid stool, the recovery in the RKM group was significantly faster by U-test than the FOM group, and a similar trend was observed overall. 4. Bacteriologically, the eradication rate of Campylobacter in the RKM group was very good at 91.3% with the FOM group showing a rate of 78.9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed1990

[Experimental and clinical studies on cefodizime in pediatrics].

Cefodizime (CDZM), a newly developed injectable cephem antibiotic, was given via bolus intravenous injection at each of 3 dose levels of 10, 20 and 40 mg/kg to each 3 children, and serum and urinary levels and urinary recovery rates were followed. A total of 57 patients received CDZM in the following regimen via bolus intravenous injection, and clinical efficacies, and microbial responses were evaluated. Mean dosage per application: 20.9 mg/kg, number of application per day: between 2 and 4 (2 times for 3 patients, 3 for 26 patients and 4 for 28 patients), mean duration of the therapy: 1 week. Patients consisted of 1 case of peritonsillar abscess, 2 acute bronchitis, 38 pneumonia, 8 urinary tract infection, 1 staphylococcal scalded skin syndrome, 2 cellulitis, 4 purulent lymphadenitis and 1 typhoid fever. In addition to the patients mentioned above 6 patients who dropped out were involved in the evaluation of adverse reactions and influence of the drug on laboratory test data, and the following results were obtained. 1. Five minutes after bolus intravenous injection in doses of 10, 20 and 40 mg/kg, serum levels determined by the bioassay method were at their maxima, i.e. 114.0, 264.6 and 461.6 micrograms/ml, respectively. Serum levels of drugs were dose-dependent throughout all the dosage levels tested. Mean serum half-lives of the drug were 1.757, 1.552 and 1.668 hours, respectively, for the 3 dose levels. Serum levels of the drug determined by the HPLC method were similar to those by the bioassay method: The maximum serum levels occurred at 5 minutes after administration, mean maximum concentrations were 105.5, 264.0 and 461.7 micrograms/ml for the 3 dose levels, and a dose response was noted for the 3 dose levels. The half-lives were 1.755, 1.598 and 1.668 hours, respectively. 2. Mean maximum concentrations in urine determined by bioassay for 2 of 3 cases received 10 mg/kg and 3 cases each given 20 and 40 mg/kg of CDZM were 884.3, 3,061 and 7,352 micrograms/ml, respectively, in the first 2 hours after administration. These levels were also dose-dependent. Mean recovery rates were 74.4, 78.4 and 71.5%, respectively, in the first 8 hours after administration. Mean maximum concentrations in urine measured by HPLC were similar to those determined by bioassay, i.e. 962.3, 3,404 and 7,899 micrograms/ml in the first 2 hours. They were, also, dose-dependent. Mean recovery rates were 82.1, 86.0 and 76.5%, respectively, in the first 8 hours after administration. The HPLC determinations gave slightly higher levels than the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1990

[Plasma methotrexate concentrations in urothelial cancer chemotherapy].

The plasma methotrexate (MTX) concentration was measured during 50 courses of chemotherapy on 26 urothelial cancer patients. A dose of 300 mg/body MTX was infused within 2 hours and plasma concentrations were measured at the scheduled times. Plasma level at the end of infusion was (2.3 +/- 0.8) x 10(-5) M/L, (2.9 +/- 1.9) x 10(-5) M/L at the 6th-hour, and (1.9 +/- 1.8) x 10(-7) M/L at the 24th-hour after the infusion. The plasma MTX concentration values were inversely correlated with creatinin clearance. In 6 cases of Kock pouch bladder, clean intermittent self catheterization of urine caused no meaningful increase of MTX.

Adult↗

PubMed1990

[A case of thoracoabdominal aortic aneurysm ruptured into the right extrapleural cavity].

A 63-year-old man of thoracoabdominal aortic aneurysm was transferred to our department. Thoracic and abdominal enhanced CT scan revealed a Crawford's type I A thoracoabdominal aortic aneurysm ruptured into the right extrapleural and retroperitoneal spaces. Without any more additional examination, graft replacement and reconstruction of a lower intercostal artery were performed with an aid of femoro-femoral bypass. Although the postoperative course was complicated by hypertension, hypoventilation and liver dysfunction, the patient recovered from the operation and 10 months later he is leading an almost normal life. Since emergency operation of thoracoabdominal aneurysm is the most courageous challenge because of the difficulties of exposure and visceral organ protection against ischemic, there have been only nine cases with successful surgery in Japan. Now we actively reconstruct lower intercostal and lumbar arteries to prevent spinal cord ischemia without ESCP monitoring in emergency cases.

Aorta, Abdominal↗