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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 325 records · Page 18Linked to original sources
PubMed1990

[High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group].

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.

Adult↗
PubMed1990

[Pharmacokinetics of BMY-28100 in multiple administration].

A multiple dose trial of BMY-28100, a new oral cephalosporin, was performed in volunteers, in order to evaluate its safety and pharmacokinetics. BMY-28100 was administered orally 250 mg t.i.d. for 7 days to seven healthy adult males. No side effects nor abnormal laboratory findings were observed. Peak levels of serum concentration and half-lives after the first and 19th administrations were 4.45 and 4.83 micrograms/ml and 1.3 and 1.1 hours, respectively. Urinary recoveries in 24 hours were 53.4% on day 1 and 56.2% on day 7. There was no tendency towards accumulation in blood upon continuous daily dosing of 250 mg t.i.d.

Administration, Oral↗
PubMed1990

[Effect of BMY-28100 on bacterial flora in adult human feces].

We investigated effects of BMY-28100 on fecal bacteria. BMY-28100 was administered orally to 8 healthy male volunteers between 20 and 24 years of age weighing between 58.0 and 79.5 kg. All subjects were given one 250 mg capsule 3 times a day at 30 minutes after meal for 7 days. Fecal bacterial counts were examined 5 days before the start of administration, the day of the start of administration, 3, 5 and 7 days after the start of administration, and 3, 5, 10, 20 and 30 days after the end of administration. Concentrations of BMY-28100 and Clostridium difficile D-1 toxin in feces were also examined together with examinations for adverse reactions and abnormal laboratory test values. 1. Total aerobic bacterial counts increased transiently upon the antibiotic dosage. Escherichia coli and yeast like organism increased transiently during the period of administration, while the total counts of anaerobic bacteria remained constant. Veillonellaceae, Peptococcaceae and Eubacterium decreased transiently during the period of administration. Although C. difficile and its D-1 toxin were detected in 1 and 5 cases, respectively, these feces appeared normal. 2. Active metabolites of BMY-28100 were not detected in the feces. 3. No adverse effects or no abnormal laboratory test values were observed.

Administration, Oral↗
PubMed1990

IgA nephritis associated with plasminogen abnormalities.

Two patients with IgA nephritis associated with hereditary plasminogen abnormalities are described. One patient had dysplasminogenemia and the other had plasminogen deficiency. In both patients, renal biopsy specimens showed significant arteriosclerotic changes in addition to mesangial proliferation. Increased fibrinopeptide A concentration in their plasma suggested increased thrombin generation. In one patient, no systemic arteriosclerosis coexisted, judging from normal optic fundi and the absence of neurological and cardiac abnormalities. In IgA nephritis, renal vascular hyalinosis is often observed, probably resulting from vascular injury. Thus, it was suggested that the decreased fibrinolysis and renal vascular injury of these patients synergistically induced more fibrin thrombi and accelerated arteriosclerosis of the kidney. These cases imply the important role of fibrinolytic disorders in the progression of IgA nephritis.

Adult↗
PubMed1990

[Pharmacokinetic and clinical evaluations of aztreonam monotherapy and aztreonam and ampicillin combination therapy in neonates and premature infants].

One-shot intravenous injection of aztreonam (AZT), a monobactam-class beta-lactam antibiotic, 20 mg/kg was administered to 4 neonates and 2 premature infants, a total of 6 cases, and plasma and urinary concentrations and urinary recovery rates were determined. Also, one-shot intravenous injection averaging 70.9 mg/kg/day of AZT alone was given to 0- to 43-day neonates and premature infants in b.i.d. to q.i.d. for an average of 8 days for the treatment (6 cases) and prophylaxis (11 cases) of infections. Furthermore, a combination therapy of AZT and ampicillin (ABPC) was applied to 0- to 79-day neonates and premature infants for the treatment (28 cases) and prophylaxis (18 cases) of infections. Average daily dosage of AZT 46.6 mg/kg was given by one-shot intravenous injection or by drip infusion in b.i.d. or t.i.d. for an average of 8 days. Average daily dosage of ABPC 78.6 mg/kg was given in the same daily frequency, route and average duration as AZT. Thus, clinical effects, prophylactic effects against infection, bacteriological effects as well as side effects and clinical laboratory test values were studied with the following results. 1. When AZT 20 mg/kg was administered to 1 case each of 6- and 7-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 5 minutes after the administration in both cases. Specifically, they were 62.9 and 72.7 micrograms/ml with AUCs of 216.6 and 231.6 micrograms.hr/ml and half-lives of 2.80 and 2.97 hours, respectively. When AZT 20 mg/kg was administered to 5- and 6-day premature infants by one-shot intravenous injection, the plasma concentrations were the highest at 15 minutes after administration in the former and 5 minutes in the latter, at values of 59.8 and 67.7 micrograms/ml, respectively. AUCs were 356.6 and 363.2 micrograms.hr/ml, respectively, and larger than AUCs of the above-mentioned neonates. Half-lives were 5.74 and 4.87 hours, respectively and longer than those of the above-mentioned neonates. When AZT 20 mg/kg was administered to 8- and 13-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 30 minutes after administration in the former and 5 minutes in the latter, at values of 43.4 and 76.9 micrograms/ml, respectively. AUCs were 202.9 and 189.8 micrograms.hr/ml, and 76.9 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Ampicillin↗
PubMed1990

[Malignant schwannoma of acoustic nerve: a case report].

During a routine physical examination in 1976, a 54-year-old man was noted to suffer from hearing difficulty and continuing tinnitus of his right ear. He had, however, no further consultations for the next five years, although the symptom persisted and gradually worsened. In May 1981, he experienced complete hearing loss in his right ear. A computed tomography disclosed no abnormalities, and other laboratory tests were unremarkable. In September 1981, the patient began to complain of paresthesia of the right angle of the mouth and tongue, right-sided facial paralysis, and walking difficulty. A repeated computed tomography showed a tumor at the right cerebellopontine angle region. A clinical diagnosis of acoustic schwannoma was made. The first operation was performed in December 1981. Complete removal of the tumor was impossible because of its unexpected, unusual hardness. The pathologic diagnosis was a malignant mesenchymal tumor, compatible with a malignant nerve sheath tumor of the acoustic nerve. A second operation was performed in January 1982, but the rapid postoperative regrowth of the tumor necessitated a third operation in March 1982. The patient died in the next month. Family histories did not show any evidence of von Recklinghausen's disease, and neither did the patient have any clinical stigmata of this disease.

Cerebellopontine Angle↗
PubMed1989

Effect of combination of 5-fluorouracil, epirubicin and mitomycin C (FEM) on advanced gastric carcinoma.

Fifteen patients with advanced gastric carcinoma were treated with the combination of 5-Fluorouracil (5-FU), Epirubicin (EPI) and Mitomycin C (MMC). Twelve of 15 patients were evaluable. Three patients showed partial response (25%) and 4 showed no change (33%) according to the criteria of Japan Society for Cancer Therapy. Mean survival time for responders, nonresponders and all evaluable patients were 14. 3, 3.6 and 6.3 months, respectively. Two patients with partial response lived over 18 months. Major toxicities included myelosuppression, nausea and vomiting, and alopecia. These were mild in general and reversible by discontinuance. No cardiotoxicity developed. It was concluded that this combination therapy is beneficial in patients with advanced gastric carcinoma because it showed measurable clinical effectiveness with less toxicity than FAM therapy (a combination of 5-FU, Doxorubicin and MMC).

Adult↗
PubMed1989

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

We have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Adult↗
PubMed1989

Inhibitory effect of Toxoplasma lysate antigen on the multiplication of transplanted tumor in mice.

Tachyzoites of the RH strain of Toxoplasma gondii were pretreated by a process of freezing and thawing followed by ultrasonication. After ultracentrifugation at 144,000 g for 120 minutes, the resulting supernatant contained a protein (TLA 144), which consisted mainly of a component of protozoan origin with a molecular weight of 10,000-20,000, and additional sugars, peptides, and amino acids. TLA 144 was soluble in water and of very low toxicity. Mice that had been inoculated with allogeneic (S-180) and syngeneic (Meth A) transplantable tumor cells, were injected intramuscularly with 100 micrograms of TLA 144 once a week for some time beginning one week after transplantation. It was found that after TLA treatment the multiplication of tumor cells was more intensely inhibited than following administration of OK-432, one of the biological response modifiers (BRMs).

Animals↗
PubMed1989

Possible involvement of prostaglandin E in development of ACTH response in rats induced by human recombinant interleukin-1.

1. Intravenous (I.V.) injection of human recombinant interleukin-1 alpha (IL-1 alpha) produced dose-dependent monophasic fevers in rats. Moreover, the I.V. injection of IL-1 alpha produced dose-dependent rises in the plasma concentrations of adrenocorticotrophic hormone (ACTH) 30 min after injections with dosages of 5 micrograms/kg and 15 micrograms/kg of IL-1 alpha. 2. The febrile responses induced by the I.V. injection of IL-1 alpha (15 micrograms/kg) were completely abolished, and conversely hypothermia occurred, when the animals were pre-treated with a cyclo-oxygenase inhibitor, indomethacin (INDO). Pre-treatment with INDO also inhibited the increase in the plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha (15 micrograms/kg), indicating that enhancement of plasma concentrations of ACTH induced by I.V. injection of IL-1 alpha is processed through the action of prostaglandins. 3. Intrapreoptic injection of prostaglandin E2 produced a dose-dependent fever with a rapid onset at doses of 25 and 100 ng. Moreover, the intrapreoptic injection of prostaglandin E2 increased the plasma concentrations of ACTH in a dose-dependent manner 30 min after injections. 4. The intrapreoptic injection of IL-1 alpha (20 ng) caused slow monophasic fever. However, no significant elevation of plasma concentrations of ACTH was observed 30, 90 and 180 min after the intrapreoptic injection of IL-1 alpha, as compared with the ACTH levels at each time in the control group which received an intrapreoptic injection of saline. 5. These results suggest that intrapreoptic prostaglandin E plays an important role in the ACTH response by inducing the release of corticotrophin-releasing factor (CRF).

Adrenocorticotropic Hormone↗
PubMed1989

Brain regions involved in the development of acute phase responses accompanying fever in rabbits.

1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses.

Acute-Phase Reaction↗
PubMed1989

[Antibiotic susceptibility and T-serotypes of group A hemolytic streptococci, clinically isolated in 1986 and 1987].

Determination of T-serotype for a total 245 strains (157 strains in 1986, 88 strains in 1987) of Streptococcus pyogenes (Group A hemolytic streptococci) isolated from clinical specimens (throat swab) of pediatric patients in Fukuoka Prefecture from 1986 until 1987 were performed. The susceptibilities of 9 antibiotics against 241 strains were studied. The most dominant strain was T-12 (57 strains, 36.3%) and followed by T-4 (32 strains, 20.4%) and T-28 (30 strains, 19.1%) in 1986. The total of these three strains was 75.8% of all strains. In 1987, T-4 (41 strains, 46.6%) was the dominant strain instead of T-12 (14 strains, 15.9%). T-28 was isolated only 4 strains (4.5%) in 1987, although it was isolated in 30 stains (19.1%) in 1986. In susceptibility-tests, no strains of 1986 and 1987 was resistant to beta-lactams. Resistant strains (MIC greater than or equal to 25 micrograms/ml) to erythromycin (EM), tetracycline (TC) and chloramphenicol (CP) were 4 (2.6%), 51 (33.3%) and 1 (0.7%), respectively in 1986. In 1987, resistant strains to EM and CP were not detected, to TC were 52 strains (59.1%), so there was an increase of susceptibility to EM and CP. As for relationship between T-serotype and antibiotic resistance, only one strain (T-12) showed multiple resistance in 1986, however in 1987, multiple resistant strain was not detected. In 1986 and 1987, 31 of 49 only TC resistant strains (63.3%) and 41 of 52 only TC resistant strains (78.8%) were T-4, respectively.

Anti-Bacterial Agents↗
PubMed1989

Characteristics of fever and acute-phase response induced in rabbits by IL-1 and TNF.

We investigated the effect of human recombinant interleukin 1 alpha (hrIL-1 alpha) and human recombinant tumor necrosis factor (hrTNF) on body temperature and acute-phase response, including changes in the plasma concentration of iron, zinc, and copper and in circulating leukocyte count. The intravenous injection of a smaller dose of either hrIL-1 alpha (0.5 micrograms/kg) or hrTNF (2 micrograms/kg) produced a monophasic fever, whereas a larger dose (hrIL-1 alpha, 2 micrograms/kg; hrTNF, 10 micrograms/kg) produced a biphasic fever. The intracerebroventricular injection of hrIL-1 alpha or hrTNF produced a dose-dependent fever. The intravenous injection of either hrIL-1 alpha or hrTNF decreased the plasma concentration of iron and zinc and increased the plasma copper concentration and the circulating leukocyte count. The intracerebroventricular injection of hrIL-1 alpha induced those responses, although the intracerebroventricular injection of hrTNF did not. The present results show that two kinds of monokines, hrIL-1 alpha and hrTNF, are intrinsically pyrogenic and induce the acute-phase response. Furthermore, it is suggested that hrIL-1 alpha induces febrile and acute-phase responses through its action on both the peripheral target organs and the central nervous system. However, hrTNF induces those responses only by its action on the peripheral target organs outside the blood-brain barrier.

Acute-Phase Reaction↗
PubMed1989

Responses of thalamic neurons in rats to skin cooling and hypothalamic temperature.

The responses of rat thalamic neurons to skin cooling were electrophysiologically examined. The responses of cold-excited neurons were classified into two types. One is a steplike response in which the activity abruptly increases with skin cooling, and the other is a graded response in which the activity gradually increases with skin cooling. The sites of these neurons were histologically identified in the ventrobasal complex of the thalamus, ventrolateral thalamus, and posterior thalamus. Two-thirds of them were found in a marginal region of the ventrobasal complex. There is no specific localization between the sites of thalamic neurons showing the steplike response and those showing the graded response. Furthermore, the effects of hypothalamic temperature on the thalamic neurons responding to skin cooling were observed. The response of thalamic neurons to cold stimulation of the skin was markedly suppressed during the hypothalamic warming. These results show that the steplike response is related to converting thermal analog signals to digital signals and that the graded response is related to relaying analog patterns of cold signals. Thermal afferent signals are modulated by hypothalamic temperature and subsequently cold sensation is modulated.

Acclimatization↗
PubMed1989

Analysis of body sway pattern after alcohol ingestion in human subjects.

Movements of the centre of gravity during 60 s of standing with eyes closed and eyes open were analysed before and after alcohol ingestion up to 8 h in 37 healthy human subjects. Blood alcohol and acetaldehyde concentrations (BAC and BAcHC) were measured simultaneously. Among the parameters analysed, area of posturogram was the most sensitive indicator; it increased to 3.8 times that of the control value at 60 min, after 3.5 ml/kg of ingested whisky (mean BAC of this group was 1.4 mg/ml), with the eyes open. The Romberg ratio, which denotes eyes closed relative to eyes open, remained constant. By contrast, there was little change in stabilometry in cases of 1.2 ml/kg of whisky ingestion (mean BAC at 60 min was 0.58 mg/ml). It is considered that body sway starts to increase when the BAC level exceeds 0.6 mg/ml on average; this value is only higher than the threshold of positional alcohol nystagmus. Correlation coefficients between BAC and each parameter of the stabilogram in the eyes open condition, such as area, X- and Y-axis diameters, and velocity of body sway, were 0.53, 0.45 and 0.48, respectively (p less than 0.01). There was no positive correlation between BAcHC and these parameters.

Acetaldehyde↗
PubMed1989

Clot lysis induced by a monoclonal antibody against alpha 2-plasmin inhibitor.

A monoclonal antibody (MoAb) to alpha 2-plasmin inhibitor designated JTPI-1 inhibited antiplasmin activity by interfering with formation of alpha 2-plasmin inhibitor (alpha 2-PI)-plasmin complex. With this MoAb, we observed plasma clot lysis in vitro and evaluated the potential of JTPI-1 to serve as a new therapeutic agent for thrombolysis. After adding 125I-labeled fibrinogen to plasma, clots were made by adding thrombin and calcium and were then resuspended in normal plasma containing various concentrations of JTPI-1. The presence of JTPI-1 enhanced release of the soluble 125I-labeled fibrin degradation fragment from the clots in a dose-dependent manner. With tissue plasminogen activator (t-PA)-depleted plasma, we showed that induction of clot lysis by JTPI-1 was dependent on fibrin-bound endogenous t-PA. Regulation of fibrinolysis initiated on the fibrin surface by fibrin-bound t-PA and plasminogen is mediated by alpha 2-PI cross-linked to fibrin by activated factor XIII. JTPI-1 bound to this cross-linked alpha 2-PI neutralized its activity and induced partial digestion of fibrin by plasmin. This resulted in additional binding of Glu-plasminogen to fibrin during the incubation. When 1.2 mumol/L JTPI-1 and 5 U/mL exogenous t-PA were present in the suspending plasma, the rate of clot lysis was essentially the same as that induced by 60 U/mL exogenous t-PA alone. These results suggest that JTPI-1 may be useful in reducing the amount of t-PA administered for thrombolytic therapy.

Antibodies, Monoclonal↗