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Biomedical subjects

H Hayasaka

Publications and source records attributed to H Hayasaka.

At least 19 recordsLinked to original sources
PubMed1995

Complex partial status epilepticus in childhood.

We report 5 pediatric patients (2 male, 3 female; age range: 4-8 years) with complex partial status epilepticus (CPSE). Four patients had previous illnesses and mild motor or mental retardation. In 2 patients, CPSE was induced by inappropriate management or selection of antiepileptic drugs. Clinical features varied and automatisms were observed in 3 patients. In 1 patient, decreased physical tone with syncope and impaired consciousness with amaurosis were observed. The episodes of CPSE were continuous in 3 patients and recurrent in 2 patients. In 4 patients, ictal electroencephalographic (EEG) findings, including video-EEG analyses of 3 patients, demonstrated persistent focal epileptic features. Intravenous diazepam abolished CPSE in 3 patients with brief periods of definite EEG localizations remaining. In 4 patients, seizure prognoses were favorable after appropriate treatments; in 1 patient, seizures were intractable even after antiepileptic drug administration.

Anticonvulsants↗
PubMed1994

Hepatocyte growth factor and its variant with a deletion of five amino acids are distinguishable in their biological activity and tertiary structure.

A naturally occurring splice variant of hepatocyte growth factor (HGF) lacks a 5-amino acid sequence in the first kringle domain. Comparison of HGF and the deletion variant (dHGF) revealed that the deletion significantly altered the biological activities, solubility, and immunological property of HGF. HGF was respectively about 20-, 10-, and 2-fold more potent than dHGF in the stimulation of DNA synthesis in human umbilical vein endothelial cells, human aorta smooth muscle cells, and NSF-60 (murine myeloblastic cells). Conversely, dHGF was respectively about 3-, 2-, and 2-fold more potent than HGF in the stimulation of DNA synthesis in LLC-PK1 (pig kidney epithelial cells), OK (American opossum kidney epithelial cells), and rat hepatocytes. Moreover, HGF was over 70-fold more soluble than dHGF in PBS. Several monoclonal antibodies raised against dHGF recognized only dHGF and neither HGF nor reduced dHGF, demonstrating that the deletion caused a tertiary structural change. The structural change in HGF may be responsible for its altered biological activities and solubility.

Animals↗
PubMed1994

Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer.

The usefulness of CAF [cyclophosphamide (CPA)/doxorubicin (ADR)/5-fluorouracil (5-FU)] + medroxyprogesterone acetate (MPA) therapy for advanced/recurrent breast cancer was studied in a randomised trial at 56 institutions. Patients received CAF therapy [CPA: 100 mg, orally, days 1-14; ADR: 30 mg/m2, intravenously (i.v.), days 1 and 8; 5-FU: 500 mg/m2, i.v., days 1 and 8) in arm I, or CAF + MPA therapy (CAF + MPA 1200 mg, daily) in arm II. The response rate was significantly higher (P = 0.041) in arm II (53.5%, 46/86) than arm I (36.6%, 30/82). The response rate by tumour site was significantly higher for lymph node and bone lesions in arm II. Partial response duration and overall response duration were significantly longer in arm II. Incidences of anorexia and nausea/vomiting were significantly higher in arm I but in arm II, moon face, oedema and vaginal bleeding were significantly higher. Many patients in arm II demonstrated improvement in performance status and weight loss, suggesting a beneficial effect of MPA. The chemoendocrine therapy with CAF + MPA appears to be more beneficial than CAF alone in the treatment of advanced/recurrent breast cancer.

Administration, Oral↗
PubMed1994

Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for breast cancer. Hokkaido Adjuvant Chemo-Endocrine Therapy for Breast Cancer Study Group.

A prospective randomised multicentre clinical study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa disease, were age 75 or below and had undergone radical mastectomy. Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX), 20 mg on the day of surgery and 10 mg the next day, followed by oral FT 50 mg day-1 for 2 years from the 14th day; treatment B, the same pattern of DOX administration for the first 2 days, followed by a combined therapy of FT and TAM 20 mg day-1 for 2 years. The number of patients was 546 (treatment A 274 and treatment B 272), of whom 34 (6%) were ineligible. The remaining 512 patients (treatment A 254 and treatment B 258) were followed up for 5 years for analysis. Significantly higher 5 year disease-free rate and 5 year survival rates were observed with treatment B compared with treatment A. When seen in terms of background factors, node-positive patients appeared to derive more benefit from tamoxifen than node-negative patients, but the oestrogen receptor-negative and premenopausal subgroups appeared to derive about the same benefit as those who were oestrogen receptor positive and post-menopausal. Indeed, survival in the premenopausal group was significantly better with tamoxifen (P = 0.04). No increase in side-effects was seen by combining TAM with FT. The study results demonstrate that concomitant administration of FT and TAM is better than FT alone for post-operative adjuvant therapy for breast cancer.

Adult↗
PubMed1994

[Early phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section].

A multi-institutional early phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 15 nationwide hospitals. KW-2307 was intravenously administered once weekly at doses of 15 to 25 mg/m2. Sixty-five among the enrolled 69 patients were eligible. Response rates were 11.8% (2/17) with 15 mg/m2, 28.0% (7/25) with 20 mg/m2 and 17.4% (4/23) with 25 mg/m2, and the overall response rate was 20.0%. Once-weekly intravenous administration of 20 mg/m2 was estimated to be the optimal dose of KW-2307 from the results. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included anorexia, nausea-vomiting, phlebitis, fever, general fatigue and stomatitis, but none of them was serious.

Adult↗
PubMed1993

[Post-gastrectomy gallstone disease].

Biliary tree of gastrectomized patients was examined with ultrasonography to investigate the factors affecting post-gastrectomy gallstone formation. Only gallbladder stone was found in 57 (18.9%). In 11 (20.0%) of 55 patients, stones had developed within 2 years after surgery, but no difference in incidence were observed by sex and age. Sixty four gastrectomized gallstone patients were examined in respect to the kind of gallstone. Patients with cholesterol gallstones were 18 (28.1%), patients with black gallstones were 29 (45.3%) and patients with calcium bilirubinate gallstones were 17 (26.6%). The incidence rate of cholesterol gallstones was lower and the rate of black gallstones and calcium bilirubinate gallstones was higher than that of non-gastrectomized patients. In conclusion, the incidence of pigment gallstones is very high in gastrectomized patients.

Adult↗
PubMed1992

[A phase II study of DWA2114R, a new platinum complex for breast cancer].

A multi-institutional phase II study of DWA2114R was conducted in breast cancer. DWA2114R at doses of 800-1,000 mg/m2 was administered by 1-hour intravenous infusion every 3-4 weeks on minimal two cycles. Fifty-two patients entered the study; 34 were eligible, 7 ineligible. Eleven patients were dropped from evaluation due to incomplete observations. There were 1CR, 6PR, 1MR, 12 NC, and 14 PD with an overall response rate of 20.6%. A median duration of responses was 11 weeks. Leukopenia and nausea/vomiting were frequently observed but well tolerated and recovery was quick. It is concluded that DWA2114R is a useful drug in the treatment of breast cancer.

Anorexia↗
PubMed1991

B-Z transition of poly(dG-m5dC) induced by binding of Lys-containing peptides.

Effects of oligopeptides containing Lys residues on the conformation of poly(dG-m5dC) have been investigated by circular dichroism spectroscopy. Lys-Ala-Lys (KAK) and its longer analogs with Lys-Ala repeats are found to convert the B-form polynucleotide to the Z form very efficiently. The ability to induce the B-Z transition is characteristic of alternating Lys-Ala sequences and increases exponentially with increasing number of the repeats. The heptapeptide KAKAKAK has an ability comparable with that of spermine, one of the most effective inducers hitherto known. The present results provide the first example of the B-Z transition of poly(dG-m5dC) induced by peptide binding.

Alanine↗
PubMed1991

Bilirubin conjugation and biliary bilirubin excretion after intravenous bilirubin injection in dogs.

This study was undertaken to investigate the bilirubin clearance, bilirubin conjugation and biliary bilirubin excretion after an intravenous single bilirubin injection (5 mg/kg or 10 mg/kg) in 10 mongrel dogs. Serum total bilirubin concentration increased after the bilirubin injection, and then it immediately decreased. Biliary excretion of loaded bilirubin induced a rapid increase of the bile total bilirubin concentration and bilirubin-monoconjugate. In the 10 mg/kg group, the increase was larger than in the 5 mg/kg group and remained high up to 4 hr after injection, whereas in the 5 mg/kg group these bile components tended to decrease and returned to the preinjection levels within 4 hr. The total bile acid concentration in the bile remained unchanged in both groups. The bile flow did not change in the 5 mg/kg group, but in the 10 mg/kg group it decreased after bilirubin loading. Significantly positive correlations were observed between total bilirubin and bilirubin monoconjugate concentrations in bile both before and 1 hr after injection, but the slopes of regression lines were markedly different from each other. These results suggest that a bilirubin load surpassing the conjugating capacity of the hepatocytes increases bile bilirubin monoconjugate and also enhances the conjugating activity in the liver.

Animals↗
PubMed1990

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of surgery].

In a nationwide study conducted in 11 surgical institutions of C-425, a newly developed human native immunoglobulin liquid preparation for intravenous injection, was combined with conventional antibiotic treatment to investigate the efficacy and safety. A total of 47 patients with severe infections which had not symptomatically responded to 3-day or longer treatment with any antibiotics was included. Doctors in charge judged the efficacy of C-425 to be "excellent" in 3 patients, "good" in 13, "fair" in 15, and "poor" in 4. Thus, a total of 16 patients (45.7%) was judged to have responded to C-425 when the "excellent" and "good" responses were combined. The number responding was 31 (88.6%) when the "fair" cases were also included. Excluding 31 patients who did not meet the Committee's criteria, the Committee judged the efficacy of C-425 in a total of 16 patients; the efficacy was "excellent" in 2 patients, "good" in 4, "fair" in 9, and "poor" in 1. The number of responding patients was 6 (37.5%) of the 16 when the "excellent" and "good" cases were combined, and 15 (93.8%) when the "fair" cases were added. Bacteriological assessment was conducted in a total of 9 patients. Causative bacteria were eradicated in 3 patients, decreased in number in 1, replaced in 2, and persisted in 3. Thus, bacteriological efficacy was observed in 6 of the 9 patients (66.7%). Neither adverse reactions nor drug-related laboratory abnormalities were observed in the 47 patients.

Adult↗
PubMed1990

Development of multiple necrotizing enteritis induced by a tumor necrosis factor-like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats.

We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin.

Animals↗
PubMed1989

[A clinical study of amino acid metabolism in cancerous hypoproteinemia--the role of branched chain amino acids (BCAA) and appropriate compositions of BCAA in parenteral nutrition].

In order to determine the nutritional effects of BCAA compositions in the treatment of cancerous hypoproteinemia, the appropriate ratio of I-leu: Leu: Val and the proportion of BCAA to Total Amino Acids were investigated. As for results, indices such as the serum albumin, the RBP and N-balance quickly recovered to normal levels when the ratio of I-leu: Leu: Val was 1.0:1.8:1.0 and the proportion o BCAA to TAA was 31%. These composition thus may be suitable for the treatment of cancerous hypoproteinemia.

Amino Acids↗
PubMed1989

[Therapeutic effect of stage III breast cancer--comparative study of preoperative intra-arterial infusion chemotherapy and non-infusion therapy].

Between January 1977 and March 1988, 111 patients of stage III breast cancer were treated in Sapporo Medical College. The median age was 51.6 years (range, 26-83 years). Menopausal status was 47 cases of premenopausal, 19 cases of perimenopausal and 45 cases of postomenopausal. Fifty-seven of these patients received intra-arterial infusion chemotherapy. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR or 4'-epi-ADR were jointly or individually made in each artery. Clinico-histological response was studied in 53 out of 57 patients. Clinical response, defined as CR + PR, was noted in 33 patients (62.3%). Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 31 patients (58.5%). Non-infusion group contained 27.7% of stage IIIb, against 72.2% in infusion group. The 5-year overall survival rates were; non-infusion group 62%, 5-FU infusion group 34.1%, and ADR MMC group 66.2%. A significant difference was seen between 5-FU infusion group and ADR-MMC group (p = 0.03). The median disease-free interval was 22.0 months (range, 1-77 months) in infusion group and 28.2 months (range, 1-124 months) in non-infusion group. MMC + ADR combination group revealed the most excellent results in terms of the 5 year survival rate and clinicohistological effect.

Adult↗
PubMed1989

[Effects of anti-toxic agents in septic shock].

From 1975 to 1987, we had 56 patients of septic shock in the Department of Surgery. Multiple organ failure occurred in many septic patients. Glucocorticoids inhibited the secretion of chemical mediators (histamine, serotonin and bradykinin) and then prevented septic shock. Intravenous administration of dexamethasone showed no change in amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood in peritonitis rats. Dexamethasone treatment of septic rats corrected FDP and nearly normalized PEP values. When glucocorticoid was given intravenously at the time of cecal incision, PFKase, PKase, G6Pase and PEPCK were stimulated, respectively. Protease inhibitor FUT-175 was infused in 5% dextrose (0.1mg/ml/hr) in septic rats. Survival time was 12.1 +/- 2.3 hour in FUT-175 group and 6.6 +/- 1.1 hr without FUT-175. In FUT-175 injected rats G6P decreased by 20%, FDP increased 50% and lactate doubled. PEP levels increased 30% above peritonitis values. The amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood were gradually decreased by pretreatment with the specific 5-lipoxygenase inhibitor AA-861 after peritonitis. Specific treatments in septic shock should be instituted administration of glucocorticoid, antibiotics, protease inhibitor and lipoxygenase inhibitor. The importance of septic shock as a factor contributing to organ failure must be acknowledge. We believe that the prompt and efficacious treatment of septic shock is the best therapy.

Animals↗
PubMed1989

[Intra-arterial infusion chemotherapy of advanced breast cancer--effects and side effects of adriamycin, 4'-epi-adriamycin and THP-adriamycin].

In 34 patients with primary advanced breast cancer, intra-arterial administration of ADR (50 mg X 3, total dose 150 mg, 10 cases), 4' epi ADR (50 mg X 3, 150 mg, 8 cases; 70 mg X 3, 210 mg, 10 cases) and THP-ADR (50 mg X 3, 150 mg, 6 cases) was performed, and its effects and side effect were analyzed. The clinical and histological response rate were superior in the ADR (150 mg) regimen and 4'-epi-ADR (150 mg) regimen. Signs of systemic toxicity such as gastrointestinal disorders, leukocytopenia and thrombocytopenia were the side effects in patients treated with THP-ADR, but the frequency of alopecia was lower. No cardiotoxicity was recorded in any of the patients. These results indicated that 4'-epi-ADR given the total dose of 150 mg in a single dosage of 50 mg was the most effective agent in intra-arterial infusion chemotherapy for advanced breast cancer.

Alopecia↗