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Biomedical subjects

Y Kubo

Publications and source records attributed to Y Kubo.

At least 145 records · Page 8Linked to original sources
PubMed1997

Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.

Animals↗
PubMed1997

[Antihypertensive effects of a novel calcium antagonist, AE0047, in various hypertensive models].

The antihypertensive effects of oral or intravenous administration of AE0047, a novel 1,4-dihydropyridine-type calcium antagonist, were investigated in spontaneously hypertensive rats (SHR/crj), one kidney-one clip renal hypertensive rats (RHR), deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DHR) and two kidney-one clip renal hypertensive dogs (RHD). AE0047 (1, 3, 10 mg/kg, p.o.) caused a dose-related reduction of systolic blood pressure (SBP) with low reflex tachycardia in SHR/crj and RHR. The effect reached its maximum at 2-4 hr after administration and was sustained for a long time. In DHR, AE0047 (0.3, 1, 3 mg/kg, p.o.) similarly showed the antihypertensive effects at 2-7 hr with no significant changes in heart rates (HR). The doses (ED30) of AE0047 required to decrease SBP by 30% were 2.6, 3.4 and 0.68 mg/kg in SHR/crj, RHR and DHR, respectively. In RHD, and AE0047 capsule (GJ-0956: 4, 8, 16, 32 mg/body, p.o.) produced dose-dependent and long lasting effects with a transient and slight increase in HR. Furthermore, the intravenous administration of AE0047 (10, 30, 100 micrograms/kg) produced the antihypertensive action slowly, reached a plateau 10 min later and then maintained for many hours. In contrast, nitrendipine (3-100 mg/kg, p.o., 3-30 micrograms/kg, i.v.) and nicardipine (1-30 mg/kg, p.o., 3-30 micrograms/kg, i.v.) exhibited a similar potency to AE0047, but these maximal effects were produced at 1-2 hr and 0.5-1 min in the case of oral and intravenous administration, respectively, with a rapid recovery in the above hypertensive rats. These results indicate that AE0047 exhibits an antihypertensive effect with a slow onset and long-lasting profile.

Administration, Oral↗
PubMed1997

[Antihypertensive effects of long-term treatment with AE0047, a novel long-lasting calcium antagonist, in hypertensive models of rats and dogs].

The antihypertensive effects of AE0047, a novel 1,4-dihydropyridine-type calcium antagonist, were investigated in spontaneously hypertensive rats (SHR/crj) and two kidney-one clip renal hypertensive dogs (RHD). AE0047, which was orally administered at the dose of 0.3, 1 or 3 mg/kg once daily for 8 consecutive weeks to SHR/crj, exhibited a dose-related decrease in systolic blood pressure. The antihypertensive action was reinforced during the drug treatment at 0.3 and 1 mg/kg. At each dose, the trough-to-peak (T/P) ratio was above 0.50 two weeks later. Although the reflex tachycardia was observed at 1 or 3 mg/kg on the 1st day, it gradually weakened within 8 weeks. Long-term treatment with AE0047 led to the regression of left ventricular hypertrophy. Furthermore, AE0047 had no influences on lipid and glucose metabolism. In RHD, and AE0047 capsule (GJ-0956) containing 2 or 8 mg of the drug was administered for 2 weeks. GJ-0956 produced no reduction in blood pressure at 2 mg, but enhanced the antihypertensive effect starting at 8 mg. The T/P ratios were 0.52 and 0.67 for the systolic and diastolic pressure, respectively, on the 14th day. These results indicate that AE0047 may be expected to exhibit beneficial effects for the clinical treatment of hypertension.

Animals↗
PubMed1997

[Granisetron versus granisetron plus methylprednisolone in the prevention of chemotherapy induced nausea and vomiting--in adjuvant chemotherapy, including CDDP against gastric cancer].

CDDP is one of the most effective drugs in chemotherapy for gastric cancer. We compared the antiemetic effect of a combination of granisetron and methylprednisolone with that of granisetron administered alone. Twenty postgastrectomy-patients who were to receive moderately emetogenic chemotherapy, including CDDP, were enrolled in randomized fashion to evaluate the efficacy and toxicity of two antiemetic regimens. The following antiemetic regimens were used: 3 mg of granisetron given intravenously before chemotherapy (11 patients) or a combination of granisetron and 250 mg of methylprednisolone in the same manner (9 patients). Granisetron combined with methylprednisolone tender to be more effective than granisetron alone. The adverse effects were very mild. Their efficacy against delayed emesis is still not entirely satisfactory.

Antiemetics↗
PubMed1997

The Alternaria alternata Melanin Biosynthesis Gene Restores Appressorial Melanization and Penetration of Cellulose Membranes in the Melanin-Deficient Albino Mutant of Colletotrichum lagenarium

Colletotrichum lagenarium and Alternaria alternata produce a dark pigment, melanin. The C. lagenarium PKS1 and A. alternata ALM genes are involved in polyketide synthesis in the melanin biosynthesis pathway. PKS1 encodes a type I polyketide synthase. For functional comparison of the ALM gene with the PKS1 gene, we examined whether the A. alternata ALM gene could restore melanin synthesis in C. lagenarium albino mutant (Pks1(-)). The ALM gene transformed the albino mutant (Pks1(-)) to melanin-producing phenotypes, designated CAL transformants. The pigment intensity of both melanized colonies and appressoria of CAL transformants was weaker than that of the wild type. Ultrastructural studies of the cell walls of appressoria demonstrated that CAL transformants formed an outer melanized layer, as did the wild type. On the other hand, the thin inner and middle layers were less electron-dense than those of the wild type. CAL transformants were able to penetrate cellulose membranes as effectively as the wild type. By contrast, the penetration frequency of CAL transformants on cucumber cotyledons was remarkably reduced compared to that of the wild type. During conidial germination, the PKS1 transcript accumulated de novo in both the wild-type and CAL transformants after the start of conidial incubation. On the other hand, ALM transcript accumulated in conidia of CAL transformants before the start of conidial incubation.

Journal Article↗
PubMed1997

The Alternaria alternata melanin biosynthesis gene restores appressorial melanization and penetration of cellulose membranes in the melanin-deficient albino mutant of Colletotrichum lagenarium.

Colletotrichum lagenarium and Alternaria alternata produce a dark pigment, melanin. The C. lagenarium PKS1 and A. alternata ALM genes are involved in polyketide synthesis in the melanin biosynthesis pathway. PKS1 encodes a type 1 polyketide synthase. For functional comparison of the ALM gene with the PKS1 gene, we examined whether the A. alternata ALM gene could restore melanin synthesis in C. lagenarium albino mutant (Pks1-). The ALM gene transformed the albino mutant (Pks1-) to melanin-producing phenotypes, designated CAL transformants. The pigment intensity of both melanized colonies and appressoria of CAL transformants was weaker than that of the wild type. Ultrastructural studies of the cell walls of appressoria demonstrated that CAL transformants formed an outer melanized layer, as did the wild type. On the other hand, the thin inner and middle layers were less electron-dense than those of the wild type. CAL transformants were able to penetrate cellulose membranes as effectively as the wild type. By contrast, the penetration frequency of CAL transformants on cucumber cotyledons was remarkably reduced compared to that of the wild type. During conidial germination, the PKS1 transcript accumulated de novo in both the wild-type and CAL transformants after the start of conidial incubation. On the other hand, ALM transcript accumulated in conidia of CAL transformants before the start of conidial incubation.

Alternaria↗
PubMed1997

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗
PubMed1997

Possible origin of murine AIDS-inducing sequence.

The murine AIDS (MAIDS) virus has a unique sequence in its gag p12 region. A transcript which hybridizes with this sequence is expressed in normal C57BL/6 mice. This transcript has been proposed to be the origin of the MAIDS virus, since the virus was originally isolated from radiation-induced leukemic C57BL/6 mice. The transcript, designated Edv, was molecularly cloned and sequenced. Compared with the nucleotide sequence of the helper LP-BM5 ecotropic virus, the pathogenic defective MAIDS virus has 16-bp deletions and a 1-bp insertion in the 5' and 3' regions of the gag p12 sequence, respectively, and the Edv transcript contains only a 3-bp deletion. Therefore, the amino acid sequence of the gag p12 region of the MAIDS virus is less homologous to that of the helper virus and Edv transcript due to the frameshift mutations. This suggested that the MAIDS virus was generated by such frameshift mutations in the gag p12 region during recombination between the helper virus and the Edv or a related sequence.

Animals↗
PubMed1997

[A case of ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade].

The ruptured thoracic aortic aneurysm is still a dramatic even with very poor outcome, whereby its survival depends largely on early diagnosis and operation. We report a successful case of aortic arch replacement for ruptured aortic arch aneurysm with cardiac tamponade. Lethal hemopericardium causing cardiac tamponade is most commonly seen as a complication of acute myocardial infarction or acute aortic dissection, and subsequent rupture of the heart or ascending aorta leads to the rapid accumulation of blood within the poorly distensible pericardial sac. Our case was operated upon emergency basis due to hemopericardium. On operative findings, the aortic aneurysm located the minor curvature of aortic arch and was a huge saccular shape. In surgical procedure, the total arch replacement was completed using selective cerebral antegrade perfusion with deep hypothermia. Postoperative course was uneventful and no cerebral complication was observed after surgery.

Aortic Aneurysm, Thoracic↗
PubMed1997

Possible mechanism of action of AE0047, a calcium antagonist, on triglyceride metabolism.

We evaluated the effect of AE0047, a dihydropyridine-type calcium antagonist, on the plasma lipid levels of obese Zucker rats. In rats treated orally with 3 to 10 mg/kg/day AE0047 for 7 days, plasma triglyceride (TG) and TG-rich lipoprotein levels dose-dependently decreased, whereas those of high-density lipoprotein cholesterol increased. Total cholesterol and low-density lipoprotein levels did not change. To elucidate the mechanism by which AE0047 decreases plasma TG levels, we examined the effect of AE0047 on the synthesis and secretion of TG-rich lipoproteins in human intestinal cell line Caco-2, as well as on the association and degradation of very low density lipoprotein (VLDL) in human hepatoblastoma cells HepG2. When Caco-2 cells were grown on a membrane filter and 14C-oleic acid was added to the apical side, 10(-5) and 10(-6) M AE0047 inhibited basolateral secretion of 14C-TG. AE0047 also suppressed the basolateral secretion of apolipoprotein B. In HepG2 cells, AE0047 increased the cellular uptake of 125I-VLDL. These results suggested that AE0047 decreased plasma TG level by the inhibition of intestinal chylomicron secretion and the enhancement of hepatic uptake of VLDL. AE0047 may be beneficial for the treatment of hypertensive patients with hypertriglyceridemia to reduce the risk factors of coronary heart disease.

Animals↗
PubMed1997

Coronary artery bypass grafting of Takayasu's disease with calcified aorta and subclavian artery obstruction.

The lesions of Takayasu's disease, which may involve the aorta and major arterial branches, may pose technical difficulties during coronary artery bypass grafting (CABG). Because the aorta is often thick and calcified, the coronary arterial lesion is often located near the coronary orifice, and the internal thoracic arteries may not be suitable for grafting due to the lesions in the subclavian arteries. A 63-year-old man with a known history of Takayasu's disease was referred to our department with chest pain complaint. Coronary angiography revealed obstruction of the left main coronary artery. CT scan showed that he had a thickened and calcified aorta. Aortography showed that both subclavian arteries had obstructive disease. Instead of using ordinary arterial grafts or vein grafts, a piece of prosthetic patch carrying saphenous vein grafts was sewn to the ascending aorta to construct the proximal anastomosis of CABG. Distal anastomosis was made on the left anterior descending artery and the obtuse marginal branch in the usual fashion. The patient showed uneventful recovery, and a postoperative coronary angiogram showed patent grafts and uncomplicated ventricular performance. This technique is useful when the aorta is not suitable for vein graft anastomosis and arterial grafts are not available as in this case with aortitis reported in the paper.

Aorta↗
PubMed1997

[Farmer's lung complicated by bilateral pneumothorax and mediastinal emphysema].

A 35-year-old woman was admitted to the hospital because of severe coughing and right-sided chest pain. She had worked on a farm for 13 years. For the preceding 2 years, she noticed a productive cough, a mild fever, and dyspnea after working in a barn for longer than 6 hours. Chest radiological examinations revealed low lung volumes, especially in the right upper lobe, and diffuse small granular shadows in both lung fields. Pathological examinations of lung specimens, which were obtained by transbronchial lung biopsy, showed alveolitis and granulomas in the interstitium. Micropolyspora faeni organisms were detected in hay from the barn. A M. faeni serum precipitation test revealed that her serum had antibodies against that organism. From these findings, we gave her a diagnosis of chronic farmer's lung. Prednisolone was given because her dyspnea and hypoxemia had increased. During the steroid treatment, bilateral pneumothorax and mediastinal emphysema developed. Bullae were removed surgically because she did not respond well to medical treatment. Although steroid administration may have caused these complications, bilateral pneumothorax and mediastinal emphysema are rare in patients with chronic farmer's lung.

Adult↗
PubMed1997

[A study on low grade malignant tumors arisen in the trachea and the bronchus].

Twelve patients who suffered from low grade malignant tumors arisen in the trachea and the bronchus (6 of carcinoid, 4 of mucoepidermoid carcinoma, and 2 of adenoid cystic carcinoma) underwent surgical treatment from 1977 to 1996 in our department. Operations included 1 sleeve resection of the trachea, 1 patch plasty of the trachea, 3 sleeve lobectomies, and 7 lobectomies. Lymph node dissection was performed in 9 of 12 cases. Metastases in lymph nodes were not found in all 12 cases. Five year survival rate of low grade malignant tumors arisen in the trachea and the bronchus was 78.8% and better than that of stage I lung cancers.

Adolescent↗
PubMed1996

Identification of domains of the cardiac inward rectifying K+ channel, CIR, involved in the heteromultimer formation and in the G-protein gating.

The cardiac inward rectifying K+ channel, CIR, and the strongly inward rectifying K+ channel, IRK1, exhibited clearly different electrophysiological properties. CIR formed a heteromultimer with the G-protein coupled inward rectifying K+ channel, GIRK1, whereas IRK1 did not, and CTR homo- and heteromultimeric channels were activated by G-protein beta 1 gamma 2 subunits (G beta 1 gamma 2), whereas IRK1 channels were not. To identify the domains of CIR involved in the heteromultimer formation with GIRK1 and in the G beta 1 gamma 2 gating, we constructed chimeras of CIR and IRK1 and examined their electrophysiological properties. The channels were divided into three domains; the N-terminal cytoplasmic domain, the C-terminal cytoplasmic domain and the residual core domain. By the analysis, it was concluded that (i) the core region of CIR, but not the N and C cytoplasmic domains, is critical for the heteromultimer formation with GIRK1; and (ii) the N and C terminal cytoplasmic regions of CIR are sufficient for the G beta 1 gamma 2 gating. We also showed that the N terminal cytoplasmic region is involved in the determination of the rate of activation upon hyperpolarization.

Animals↗