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T Onishi

Publications and source records attributed to T Onishi.

At least 163 records · Page 9Linked to original sources

[In vivo anti-tumour efficacy of tumour necrosis factor and interferon- alpha, -gamma on human renal cell carcinoma heterotransplanted in nude mice].

Using human renal cell carcinoma heterotransplanted in nude mice (JRC 11: anaplastic and alveolar pattern, grade IV), the in vivo anti-tumour efficacy of tumour necrosis factor (rHu-TNF-alpha: PT-050) and IFN-alpha (nHu-IFN-alpha: HLBI), IFN-gamma (nHu-IFN-gamma: OH-6000) were investigated. The dose of TNF was 1,000, 3,000, 10,000 J.R.U. (i.p., every day), that of IFN-alpha was 1 x 10(4) and 1 x 10(5) I. U. (s.c., every day) and that of IFN-gamma was 1 x 10(4) and 1 x 10(5) I.U. (s.c., every day). Mono-therapy of TNF, IFN-alpha and IFN-gamma was not effective with regard to tumour regression rates, histological degeneration rates and survival time of the host mice. Combination therapy of TNF and IFN-alpha, IFN-gamma were also not effective with regard to tumour regression rates, but when considering histological change, sporadic disappearance of endothelium of intra-tumoural vasculature, flow of tumour cells clustered in intra-vascular cavity, and extra-vascular bleeding were observed. With special reference to survival of host mice, prominent prolongation of survival time in combination treatment, especially in TNF combination therapy groups with the dosage of 10,000 J.R.U. was observed. Therefore we concluded that there is no synergistic reaction in combination therapy of TNF and IFN against JRC 11 tumour. But combined activity of TNF and IFN on the vasculature of renal cell carcinoma (JRC 11) and the suppression of cachexia related condition were detected.

Animals↗

[A case of recessive dystrophic epidermolysis bullosa associated with dwarfism with special reference to pathophysiological role of growth hormone].

Epidermolysis bullosa is a group of disorders whose common primary feature is the formation of blisters following trivial trauma. Recessive dystrophic epidermolysis bullosa (RDEB), a subtype of epidermolysis bullosa, is frequently associated with growth retardation. This growth retardation has been reported to be caused by trophopathy following protein loss through skin lesions. Endocrine disorders as the cause of growth retardation in RDEB have not been clearly described. An 11-year-old female had a typical RDEB with dwarfism. Her height was 125 cm and weight was 21 kg, both of which were 2.5 SD below the average. The skin lesions were generalized and probably caused by undernourishment, infection, and blood loss through the skin. However, her serum albumin was at the lower normal limit, and the rapid turnover proteins were slightly decreased. Endocrinological examinations revealed that all the basal levels of pituitary, thyroid, and adrenal hormones were normal. Results of the exercise test, the insulin tolerance test, and the growth hormone-releasing factor test indicated the presence of hypothalamic disorder in secretion of growth hormone. This is the first report of RDEB in which hypothalamic disorder in growth hormone secretion was investigated. On the other hand, growth hormone is known to be involved in collagen metabolism, and a decrease in collagen fibrils and an increase in collagenase activities are found in the skin of RDEB. This implies that this hypothalamic disorder in growth hormone secretion may be involved in the pathophysiology of both dwarfism and the skin lesions in RDEB.

Child↗

Influence of differences in tumor vascularity upon the effects of hyperthermia.

Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5 degrees C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.

Animals↗

Monoclonal antibody against human enterokinase and immunohistochemical localization of the enzyme.

A monoclonal antibody, hek-1, was raised against enterokinase or enteropeptidase that had previously been partially purified from human duodenal fluid. Hek-1 showed staining of two glycoprotein bands of relative molecular weights of 260,000 and 240,000 on immunoblot analysis of partially purified enterokinase and of ammonium sulfate fraction of duodenal fluid. An enzyme immunoassay for human enterokinase was developed, making use of hek-1. Sensitivity to enterokinase was 20 times higher than that of the conventional assay where BAPA was used as a substrate. The immunohistochemical study with hek-1 showed staining of the brush border membrane and some goblet cells of the duodenum and upper jejunum but no staining of the colon epithelium.

Animals↗

Detection of the spatial distribution of late potentials by body surface mapping using forty-five unipolar, leads.

For evaluating the spatial location of late potentials (LPs), the authors designed a new system for the body surface mapping of signal-averaged, filtered ECGs using forty-five thoracic unipolar leads (5 x 9 array). The signals from patients with old myocardial infarction (MI, N = 7) and arrhythmogenic right ventricular dysplasia (ARVD, N = 1) were amplified and passed through a bandpass (100-300 Hz) filter. The departure maps, LP isopotential maps, and LP30 area maps were generated and superimposed. The LP30 duration was determined as the section between the filtered QRS endpoints and points thirty milliseconds (ms) before. Isopotential maps of the LPs showed distinct positive and negative regions. In 7 cases with MI, the extreme was related to the zones indicated by the departure maps, and the LP30 area maps also corresponded to the departure areas. In 1 case of ARVD, endocardial fragmented activity directly recorded at the right ventricle closely corresponded with the region on the LP30 area map. In conclusion, body surface LP isopotential maps and LP30 area maps may provide useful information concerning the spatial distribution of endocardial fragmentation.

Arrhythmias, Cardiac↗

Lipid metabolism in acromegalic patients before and after selective pituitary adenomectomy.

Lipid metabolism was studied in 16 acromegalic patients who all underwent transsphenoidal selective pituitary adenomectomy (SPA). Before the operation, their serum lipid levels correlated with none of the basal levels of serum growth hormone (GH), basal levels of plasma somatomedin-C (SM-C), fasting levels of plasma glucose (FPG), peak levels of plasma glucose (PGp) or basal and peak levels of serum immunoreactive insulin (IRIb and IRIp, resp.) in the oral glucose tolerance test (OGTT), and obesity indices. The serum GH levels as well as plasma SM-C levels in the group with decreased serum high density lipoprotein-cholesterol (HDL-C) differed greatly from those of the normal HDL-C group. However, there was no significant difference in either serum GH or plasma SM-C between groups with and without metabolic abnormality of any other lipid examined. After the operation, the basal levels of serum GH and plasma SM-C decreased significantly. In conjunction with these changes, PGp, serum IRIb, serum triglyceride (TG), non-esterified fatty acid (NEFA) and very low density lipoprotein (VLDL) decreased significantly. In contrast, serum HDL-C increased significantly. However, FPG, serum IRIp, obesity indices, serum total cholesterol (TC) and serum low density lipoprotein (LDL) showed no significant change. There were no significant differences in the levels of any serum lipid either before or after surgery among the diabetic, borderline and normal types defined by the preoperative OGTT patterns. Atherogenic indices (AIs) decreased significantly and returned to normal postoperatively. These results suggest that obesity or secondary diabetes is not a direct cause of hyperlipidemia in acromegaly. The prognosis of acromegaly is affected by arteriosclerotic complications. It is intriguing, therefore, that AIs were normalized by transsphenoidal SPA. Being rather a safe procedure, it can be performed without hesitation, aside from a conservative treatment.

Acromegaly↗

Dolichoectatic basilar artery treated by reducing hemodynamic stress--report of two cases.

Two cases of dolichoectatic basilar artery with a mass effect to the brainstem structure were treated by reducing hemodynamic stress. In one case, angiograms showed the dolichoectatic basilar artery creating a turbulent flow in the vertebrobasilar junction, and unilateral vertebral artery clipping in addition to posterior fossa decompression was performed. The other case, a combination with bilateral internal carotid artery occlusion, underwent bilateral superficial temporal artery-middle cerebral artery anastomoses. The possible surgical treatments of dolichoectasia are discussed.

Adolescent↗

[67Ga-citrate scintigraphy in patients with fever of unknown origin].

67Ga scintigraphy was performed in 49 patients with fever of unknown origin (FUO). Positive findings were observed in 25 patients out of 49 (51%). Occult focal lesions were demonstrated in 4 patients and useful information for the diagnosis was provided in 4 patients. In short, the examination showed diagnostic usefulness in 8 (32%) out of positive cases. 67Ga scintigraphy may be recommended as a further examination for patients with strongly suspected focal lesion in FUO.

Adult↗

[A clinicopathological study of signet-ring cell carcinomas of the stomach].

Surgically resected signet-ring cell carcinomas of the stomach have been clinicopathologically investigated. Although this type of carcinoma was found to be widely spread in the propria mucosa, a deeper invasion beyond the submucosa appeared more slowly than in other types of carcinomas. For example, the larger the early carcinoma in which the invasion was restricted to within the submucosa, the greater the incidence of a signet-ring cell carcinoma increase, especially in cases involving the mucosa. The incidence of a nodal metastasis was found to be lower than in cases of a moderately and poorly-differentiated adenocarcinoma in the early stage. However, when the signet-ring cell carcinomas invaded beyond the submucosa, the tumor cells spread rapidly and widely in the wall with a subsequent abdominal implantation, causing ascites and peritonitis carcinomatosa. It seemed likely that this deep invasion was accelerated by cellular change, such as the enlargement of nucleus, cellular atypy, and a decreased mucin production. As signet-ring cell carcinoma arise from the neck of glands and infiltrate the propria mucosae under the superficial epithelium, diagnosis by the barium enema and an endoscopic examination is very difficult in the case of small-size lesions. In lesions greater than 1 cm in diameter, these carcinomas usually showed an erosive and/or ulcerated appearance.

Adenocarcinoma, Mucinous↗

[Comparative study of the patients with renal cell carcinoma before and after 1980].

Patients with renal cell carcinoma treated at Jikei University and affiliated institutions were studied with regard to temporal differences. Our study population was divided into two groups: an earlier group comprising 169 patients treated between January 1957 and December 1979, and a later group comprising 165 cases treated between January 1980 and December 1984. The mean age in the earlier group was 56.2 years, while that in the later group was 60.4 years. Therefore, the patients in the earlier group were generally younger than those in the later group. Patients in the earlier group were more likely to present with urinary symptoms at the time of diagnosis. On the other hand, patients in the later group were more likely to present with extra-urinary symptoms or to be asymptomatic. The time period between the onset of symptoms and initial consultation with physician was longer (within one month) in the earlier group. Most patients in the later group underwent nephrectomy using the transperitoneal or thoracoabdominal approach. Few patients in the later group were treated with radiotherapy. As adjuvant chemotherapy, MFC (MMC, 5-FU and Ara-C) or MACV (methotrexate, actinomycin D, cyclophosphamide and vincristine) regimen were most commonly employed in the earlier group. FAV (5-FU, adriamycin and vinblastine) regimen or interferon therapy which was classified as biological response modifiers (BRM) were more commonly employed in the later group. More cases were diagnosed as stage II in the earlier group, and more cases were diagnosed as stage IV in the later group. No significant differences were observed between the earlier and later groups, with regard to 5- and 10-year survival rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serum hemolytic activity in dogs infected with Babesia gibsoni.

The hemolytic activity in serum of Babesia gibsoni-infected dogs was examined. When the activity was assayed in a reaction system consisting of similar concentrations of the serum and canine red blood cells to those in blood, significant hemolysis was observed. The activity of the serum of B. gibsoni-infected dogs, either naturally or experimentally, was always higher than that of uninfected animals. Moreover, in the experimental infection with B. gibsoni, the change in serum hemolytic activity was parallel to those of anemia and parasitemia, whereas it was inversely parallel to that of the hematocrit value. The present study revealed the presence of a hemolytic factor(s) in the serum of B. gibsoni-infected dogs, suggesting that the progressive anemia was due to hemolysis by the factor(s).

Anemia, Hemolytic↗

Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain.

A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF.

Antibodies, Monoclonal↗

Effects of valinomycin on calcium mobilization in vascular smooth muscle cells induced by angiotensin II.

The effect of the specific potassium (K+) ionophore valinomycin on increase in intracellular calcium concentration [( Ca2+]i) was studied in vascular smooth muscle cells (VSMC). Valinomycin at more than 10(-9) M dose-dependently suppressed phasic increase in [Ca2+]i in VSMC induced by angiotensin II (AII) in both control and Ca2+-free solution, indicating that it suppressed the release of Ca2+ from intracellular Ca2+ stores. Nicorandil and cromakalim, which are both K+ channel openers, also suppressed the increases in [Ca2+]i induced by AII in the Ca2+ free solution. However, valinomycin did not suppress AII-induced production of inositol 1,4,5-trisphosphate (IP3), which is known to mediate the release of Ca2+. These results indicate that decrease of intracellular K+ induced by valinomycin suppressed the release of Ca2+ from intracellular Ca2+ stores induced by IP3.

Angiotensin II↗

Effects of very-low-calorie diet weight reduction on glucose tolerance, insulin secretion, and insulin resistance in obese non-insulin-dependent diabetics.

We put 12 obese subjects on a very-low-calorie diet (VLCD) and observed how their weight loss affected their glucose tolerance. Seven had non-insulin-dependent diabetes and five did not. They consumed 1000 kcal/day for at least 1 week, then 420 kcal/day for 4 weeks, and 1000 kcal/day thereafter. VLCD improved glucose tolerance and insulin response to a glucose load in the diabetics and did not affect these parameters in the non-diabetics. It did not change insulin responsiveness to intravenous glucagon in either group. Both groups showed improved insulin resistance, as measured by an insulin suppression test. Regression analysis showed that insulin resistance correlates well with obesity and glycemic control. Weight reduction did not change hepatic insulin extraction. Thus, the improvement in glucose tolerance by some of the diabetics seems to have arisen from improvements in their insulin resistance and insulin response to a glucose load. Insulin resistance improved because of weight reduction and subsequent improvements in glycemic control.

Adult↗

[Clinical study of undifferentiated renal cell carcinoma in comparison with well differentiated cases].

UNLABELLED: During the past 28 years, 397 patients with renal cell carcinoma were treated at The Jikei University Hospital and its related institutions. Of these, 44 cases with undifferentiated renal cell carcinoma (grade IV) were compared with well differentiated cases (grade I), with regard to following 5 clinicopathological items: 1) general clinical features such as distribution of patient ages, sex ratio, affected side, the relationship of age and the volume of nephrectomized kidney, 2) angiographic appearance, 3) distribution of stages, 4) distribution of metastatic organs, 5) survival rates of each grade and each stage. THE RESULTS: 1) There was no specific trend in the distribution of affected ages, sex ratio and affected side of the tumour, but the volume of nephrectomized kidney in grade IV cases was much larger than that of the kidneys in grade 1 cases. Furthermore, in grade IV cases, the older the patient, the much lighter was the nephrectomized kidney. 2) No specific trends were observed in the angiographic pattern in the two groups. 3) Regarding stages, 75% of patients with the grade IV had stage IV carcinoma. But, 69% of patients with grade I had stage I. 4) Grade IV patients had a high incidence of lung and liver metastasis compared with grade I, which had a high incidence of bone metastasis. 5) Patients in grade IV and in grade I with stages I-III carcinomas lived longer than any grade with stage IV. So the undifferentiated renal cell carcinoma should be treated with adjuvant therapy even in low stage.

Adult↗

Association of increased intracellular free Ca2+ by platelet-derived growth factor with mitogenesis but not with proteoglycan synthesis in chondrocytes--effect of suramin.

The effects of platelet-derived growth factor (PDGF) on the intracellular free Ca2+ concentration [( Ca2+]i) in chondrocytes were studied with a fluorescent Ca2+ indicator, fura 2, and compared with the effects of PDGF on mitogenesis and proteoglycan synthesis. PDGF evoked phasic and then tonic increase in [Ca2+]i dose-dependently in quiescent cultures of chondrocytes, and it also stimulated both DNA and proteoglycan syntheses dose-dependently similar to somatomedins. Suramin, which inhibits the interaction of PDGF with its receptors, caused dose-dependent inhibition of both the PDGF-evoked increase in [Ca2+]i and stimulation of DNA synthesis by PDGF. However, suramin rather enhanced the proteoglycan synthesis induced by PDGF without affecting the basal level of proteoglycan synthesis directly. These results suggest that [Ca2+]i may be an important signal for the action of PDGF on cell proliferation in chondrocytes, and that the initial signal for proteoglycan synthesis is different from that for DNA synthesis induced by PDGF after the activation of PDGF receptor.

Animals↗

Hyperthermia with simultaneous administration of interferon using established human renal carcinoma heterotransplanted in nude mice.

Using human renal carcinoma heterotransplanted in nude mice, the effects of the combined use of hyperthermia and interferon (natural human interferon-alpha; IFN-alpha, and recombinant interferon-gamma; IFN-gamma) were examined. The hyperthermic device used was the Clini-Therm, Mark VII, 915 MHz, microwave. The administration of interferon was started immediately before hyperthermia and carried out on consecutive days. The combined use of hyperthermia and IFN was compared with hyperthermia and with IFN alone. The combined use of hyperthermia and IFN-alpha was shown to have significant anti-tumour effects compared with the former or latter alone. Of 10 nude mice (10 implanted tumours) used for the experiment, 5 showed complete disappearance of the implanted tumours and the others showed prolongation of survival. Combined treatment with IFN-gamma and hyperthermia showed no significant effect when compared with other treatment groups. Combined treatment with local hyperthermia and IFN-alpha may have some application to the clinical management of renal carcinoma.

Animals↗