Effect of feline leukemia virus on the development of plaque forming cells in feline peripheral blood lymphocytes.
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Biomedical subjects
Publications and source records attributed to Y Hirota.
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We investigated the natural course of 59 patients with hypertrophic cardiomyopathy (HCM) in follow-up periods of one to 13 years and analyzed the clinical, hemodynamic and echocardiographic parameters to determine the factors influencing the prognosis. Among these patients, 44 (75%) remained stable in a compensated condition with or without medications. Five patients died suddenly and two died of congestive heart failure. Heart failure developed in another eight. At the initial evaluation, these 15 patients had high left ventricular end-diastolic pressure (mean: 22 +/- 8 mmHg) significantly higher than that of 44 compensated patients (mean: 13 +/- 6 mmHg, p less than 0.001). There were no differences in age at the initial evaluation between compensated and end stage groups. Atrial fibrillation occurred persistently in three and transiently in two among ten patients with heart failure during follow-up periods. Ventricular dimensions and systolic function did not statistically differ between the two groups. However, six patients with heart failure had cavity dilatation and deteriolated ventricular contractile function at the initial evaluation. Four of them did not show any change in left ventricular hypertrophy, but the regional thinning of the wall was observed in the remaining two. There were no characteristic features to predict sudden death in the clinical, hemodynamic or echocardiographic parameters. Thus, increased left ventricular end-diastolic pressure, atrial fibrillation, left ventricular dilatation and the regional thinning of the left ventricular wall are useful predictive markers for poor prognosis in HCM.
The chemotherapeutic effects of cisplatin + adriamycin + cyclophosphamide (PAC) on 50 epithelial ovarian cancers were compared with the effects of 5-fluorouracil + cyclophosphamide + mitomycin C (FAM) in 17 patients. The cumulative survival at 5 years was 61.1% in all patients, 62.5% in patients treated with PAC and 54.7% in patients treated with FAM. The 5-year survival rate was 100% in Stage I, 63.5% in Stage II, 40.1% in Stage III and 22.2% in Stage IV. Of 22 patients with Stage III and IV treated with PAC, 16 patients responded (8CRs + 8PRs). The median survival duration of the treated patients was 19 months. On the other hand, of 8 patients treated with FAM, only one patient responded (PR). The median survival duration was 7 months. These results indicated the effectiveness of PAC chemotherapy against advanced ovarian cancer. No severe toxicity was observed during treatment with PAC or FAM.
The major structural difference between p60c-src and p60v-src resides in the carboxy-terminal region. We introduced substitution, replacement and deletion into the carboxy-terminal region of chicken p60c-src and examined the effects on its biochemical and biological properties in chicken embryo fibroblasts. The replacement of the carboxy-terminal region after amino acid position 515 of p60c-src with the corresponding region of p60v-src converted p60c-src to a transforming protein with elevated kinase activity. The substitution of Tyr527, which is a major tyrosine phosphorylation site of p60c-src, with phenylalanine resulted in an increase of kinase activity and in transforming ability. On the other hand, a deletion after position 515 abolished the kinase activity. These results revealed the structural features of the carboxy terminus of p60c-src that are required for the regulation of its intrinsic protein kinase activity.
Experimental chemotherapy was performed using the human tumor-nude mouse system. The tumors were mucinous cystadenocarcinoma (OVA-1), undifferentiated carcinoma (OVA-2), endometrioid adenocarcinoma (OVA-3), serous cystadenocarcinoma (OVA-4) and three yolk sac tumors (YST-1, -2, -3). The drugs tested were adriamycin, bleomycin, cisplatin, cyclophosphamide, 5-fluorouracil, ifosfamide, mitomycin C, vinblastine, etoposide and teniposide. The dosages employed here were about one-third and one-ninth of the LD50 used for conventional mice. The results obtained were as follows: 1 A clear correlation between the antitumor activity of the drug and the histological type of the tumor was observed. The results indicated the importance of making a chemotherapeutic protocol according to the histological type of the individual tumor. 2 The antitumor activity depended on the dosage of the drug. The results suggested that it was necessary to increase the dosage of the anticancer drugs to obtain further clinical effects on patients with ovarian cancer. 3 The administration of a single drug in a sufficient dosage produced more effective antitumor activity rather than multidrug treatment. The results suggested that combination chemotherapy might not necessarily be the best way to effectively treat patients with ovarian cancer.
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A method for noninvasively determining left ventricular (LV) end-systolic pressure (ESP) using carotid pulse tracings and cuff-measured blood pressure was re-evaluated. It was validated during diagnostic cardiac catheterization in 60 patients with cardiovascular diseases. LVESP calculated by this method and systolic blood pressure measured by the cuff were compared with aortic dicrotic notch pressures obtained by a catheter-tip manometer system as true LVESP. The calculated ESP was measured by the following formula; [the ratio of the excursion of dicrotic notch (b) to the peak (a) in carotid pulse tracings: (b/a) x pulse pressure] + diastolic blood pressure. This calculated ESP had a high correlation coefficient with true ESP invasively measured (r = 0.96), but was estimated to be 5.3 +/- 5.0 mmHg less than true ESP. Systolic blood pressure, used as a noninvasive index of ESP, accurately estimated ESP, but it was higher by 14.8 +/- 11.2 mmHg (r = 0.84). Calculated ESP measured by the present method was not affected by age or systemic vascular resistance. This is a reliable noninvasive means of estimating LV end-systolic pressure. Compared with the peak arterial pressure, this is a better parameter for the analysis of LV contractility, such as stress-shortening, and end-systolic pressure-volume relations.
The chemotherapeutic effects of CDDP, CBDCA and CHIP on human ovarian cancers heterotransplanted into nude mice (mucinous cystadenocarcinoma OVA-1, poorly differentiated adenocarcinoma OVA-2, endometrioid adenocarcinoma OVA-3, serous cystadenocarcinoma OVA-4, and three yolk sac tumors YST-1, YST-2, YST-3) were examined. OVA-1 did not respond to CDDP, although it responded well to CBDCA and CHIP. OVA-2 responded well to all these platinum analogs. OVA-3 responded well to CDDP, but did not respond to CBDCA or CHIP. OVA-4 responded well to CDDP and CBDCA, but did not respond to CHIP. Tumors YST-2 and YST-3 exhibited broadly comparable sensitivity to CDDP and the two other analogs, and YST-1 was substantially more sensitive to CDDP than to CBDCA or CHIP. The results indicated the necessity of selection of platinum analogs according to the histological types of tumor for the effective treatment of ovarian cancer.
A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
To overcome the dose limiting toxicity of cisplatin we administered high-dose (12 mg/kg) cisplatin together with hypertonic (3%) saline to tumor-bearing nude mice three times at four day intervals. The heterotransplanted human ovarian tumors consisted of a mucinous cystadenocarcinoma (designated as OVA-1), a poorly differentiated adenocarcinoma (OVA-2), an endometrioid adenocarcinoma (OVA-3) and three yolk sac tumors (YST-1,-2,-3). The mean volumes of the tumors in animals treated with a standard dose 6 mg/kg of cisplatin in 0.9% NaCl or 12 mg/kg of cisplatin in 3% NaCl were, as a percentage of the mean tumor volume in untreated animals: 51 and 26 for OVA-1, 28 and 15 for OVA-2, 11 and 7 for OVA-3, 7 and 14 for YST-1, 3 and 12 for YST-2, and 11 and 10 for YST-3, respectively. The most interesting result was that a high dose (12 mg/kg) of cisplatin succeeded in producing a strong antitumor effect on mucinous cystadenocarcinoma (OVA-1), which was resistant to standard dose cisplatin (6 mg/kg). A comparison of the body weight of tumor-bearing nude mice before and on Day 30 of treatment did not show any appreciable treatment-related changes.
The significance of maintenance chemotherapy after surgery for ovarian cancer was examined using a human tumor-nude mouse system. Experiment 1: The human yolk sac tumor of the ovary (YST-2) heterotransplanted into nude mice was used. The tumor-bearing mice were administered 100 mg/kg of 1-Hexylcarbamoyl-5-fluorouracil (HCFU) orally for 60 days after tumor resection. Control mice were given 0.1 ml 0.3% methylcellulose after tumor resection. When the tumor was completely resected by surgery, HCFU treatment succeeded in decreasing the recurrence rate of the tumor, and in improving the survival rate of the host mice. However, when the macroscopic tumor was left in the host mouse, HCFU treatment did not affect either the recurrence rate of the tumor or the survival rate. Experiment 2: The human poorly differentiated adenocarcinoma of the ovary (OVA-2) heterotransplanted into nude mice was used. Administration of 100 mg/kg of HCFU immediately after the heterotransplantation into nude mice for 60 days suppressed the tumor growth. HCFU treatment improved the survival rate of the tumor-bearing mice. The antitumor effect of HCFU on the OVA-2 tumor was confirmed by histological examination. These experiments revealed that the maintenance chemotherapy after surgery for ovarian cancer was important in the effective treatment of the patient (tumor-bearing host).
Thirteen patients with gynecologic cancer were treated with ifosfamide (2 g X 5), cisplatin (70 mg/m2) and adriamycin (20 mg/m2) combination chemotherapy. The response rate of 7 evaluable patients was 43%, with a median duration of survival of 14 months. Six patients with non-measurable disease are currently free from disease with a median duration of survival of 18 months. This combination caused reversible myelosuppression. No hemorrhagic cystitis was observed.
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N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was administered PO to 76 patients with acute leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative disorders (MPDs). Of 20 patients with acute myelogenous leukemia, 2 achieved complete remission, and the only patient with acute lymphoblastic leukemia achieved partial remission. Remission was reached with PLAC 100-300 mg/day 25-66 days after the start of therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of therapy. Improvement of polycythemia was observed in all 5 patients with polycythemia vera, and reduction of thrombocytosis was observed in 5 out of 6 patients with essential thrombocythemia and myelofibrosis. An antileukemia effect was noted in 1 of 5 with chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute leukemia compared with its parent compound, this antileukemia Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute leukemia of the aged, a condition for which intensive chemotherapy is not appropriate.
The cardiac function of nine patients who had various cardiovascular diseases was investigated by echocardiography during dental treatment in which local anesthetics were administered. The administration of lidocaine with epinephrine enhanced the cardiac output of all patients. Increased heart rate was responsible for the increased cardiac output in four cases, whereas increased stroke volume was responsible in the other five cases. The administration of prilocaine with felypressin caused less of an increase in cardiac function than did lidocaine, with only one patient showing a significant change in cardiac dynamics.