[The studies on the blood supply of metastatic liver tumor induced by VX2 using BrdU].
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Biomedical subjects
Publications and source records attributed to H Taniguchi.
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The technique for repair of large defects in the diaphragm by the use of an ipsilateral or contralateral flap from the external oblique abdominal muscle was successfully used during five hepatic resections and has been described herein.
In order to deliver a high concentration of CDDP in tumor tissue, we attempted to infuse CDDP intra-arterially for preoperative patients with resectable gastric cancer. Thirty-two patients (21 males and 11 females) were treated. The concentration of platinum was measured in cancer tissue, normal mucosa, lymph nodes without metastasis at the greater curvature. These were gathered operatively and in serum just before operation. The serum concentration of free-CDDP was also measured. Student's-t test was performed with the data. After intra-arterial injection of 60 mg CDDP, the mean concentration of platinum in cancer tissue was 1.11 +/- 0.45 microgram/g and after intravenous injection of 40 mg CDDP that was 0.30 +/- 0.11 microgram/g. After intra-arterial injection of 40 mg CDDP, the mean concentration of platinum in cancer tissue was 0.64 +/- 0.12 microgram/g, which was significantly higher than in normal gastric mucosa (0.27 +/- 0.06 micrograms/g) or serum (0.37 +/- 0.10 micrograms/ml) (p less than 0.025). The mean concentration of platinum in cancer tissue was higher than in the lymph nodes (0.45 +/- 0.10 micrograms/g), but there was no significant difference. In sera the concentrations of free-CDDP were all under the detectable limit. It was concluded that intra-arterial injection therapy of CDDP was an effective method to maintain a high concentration of CDDP in gastric cancer tissue.
To compare the pharmacological advantage of intra-arterial, intraportal and intravenous administration of anticancer drug for metastatic liver tumor, BrdU was administered to rabbits with metastatic liver tumor of VX2 from various routes and taken up into the nuclei of tumor cells. Both one-shot injection and continuous infusion (30 min) of BrdU was performed from celiac artery, portal vein or peripheral vein. In some rabbits, the portal vein or the celiac artery was ligated to form one blood supply to the liver. After the administration of BrdU, the liver was removed. The samples were stained by the immunohistochemical procedure using monoclonal antibody to BrdU. The result was that the drug uptake of small metastatic liver tumor by both arterial and portal one-shot injection was good, and the uptake following intra-arterial injection of BrdU was superior to its intraportal injection in large metastatic tumor. However, only peripheral cells of large tumor took up BrdU after intra-arterial injection and inner cells of large tumor did not take up BrdU after any continuous infusions. The intraportal and intravenous administration of BrdU without ligation of celiac artery had the same effect as its intra-arterial administration.
Human adherent monocytes stimulated with 1 microgram/ml pertussis toxin (PT) produced interleukin-1 (IL-1), as measured by thymocyte co-stimulation assay and enzyme-linked immunosorbent assay (ELISA), specific for IL-1 alpha and IL-1 beta. To clarify the role of protein kinase C (PKC) and calmodulin in IL-1 production, we investigated the effects of a PKC inhibitor, H-7, and a calmodulin antagonist, W-7 on PT- and lipopolysaccharide (LPS)-induced IL-1 production by monocytes. Addition of 10 microM and 20 microM H-7 to the culture medium markedly suppressed both PT- and LPS-induced IL-1 production. PT-induced IL-1 production was significantly suppressed by 5 microM and 10 microM W-7. However, LPS-induced IL-1 production was not suppressed by W-7 at the concentrations tested. When monocytes were labelled with Quin 2/AM, IL-1 production by monocytes stimulated with PT and LPS was markedly suppressed. These results indicate that different pathways are involved in the IL-1 production by PT and LPS; both calmodulin- and PKC-dependent processes are necessary for the IL-1 production induced by PT, whereas LPS-induced IL-1 production is dependent on the PKC. Inhibition of IL-1 production by interfering with intracellular Ca2+ trafficking in Quin 2/AM-loaded monocytes may be associated with the inhibition of PKC and calmodulin activity.
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A 52-year-old man, who had undergone right upper lobectomy because of active tuberculosis 29 years before, was admitted with complaints of severe cough and expectation. Two years ago, he had pulmonary aspergillosis and was successfully treated with some anti-mycotic agents. This time his chest X-P showed fungus ball in a residual tuberculous cavity in the right upper field and he was diagnosed as pulmonary aspergilloma from the results of radiological findings, sputum culture, and serologic test. By bronchofiberscopy fungus ball was observed. With transbronchial infusion of Amphotericin B, intravenous administration of Miconazole and oral administration of Flucytosine, clinical symptoms have improved and lysis of fungus ball was observed. Sputum culture revealed Aspergillus flavipes group. Bronchopulmonary aspergillosis, which was incurable by surgical treatment because of underlying disease, was successfully treated with transbronchial infusion of Amphotericin B and administration of some anti-mycotic agents.
The effect of caerulein on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. Prolonged alternate-day administration of caerulein at 10 micrograms/kg body weight after treatment with the carcinogen for 20 weeks significantly increased the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that treatment with caerulein had no influence on the histology of induced adenocarcinomas. Furthermore, administration of caerulein resulted in a significant increase in the bromodeoxyuridine-labeling indices of the antral mucosa but did not influence the bromodeoxyuridine-labeling indices of the fundic mucosa and the carcinomas. These findings indicate that caerulein enhances gastric carcinogenesis and that the effect may be related to the promoting effect of caerulein on cell proliferation in the antral mucosa.
We evaluated cryopreservation techniques for pancreatic fragments and islets using rat tissue. After equilibration in 10% dimethyl sulfoxide (Me2SO), the tissue was frozen in a programmable freezer at 1 degree C/min down to -40 degrees C and at 3 degrees C/min down to -71 degrees C. The islets, when thawed, released abundant insulin in the presence of as little as 3.3 mM glucose, much more so than non-frozen islets did. Three additional procedures, prefreezing and post-thawing culture and the stepwise dilution of the Me2SO, lowered the non-specific insulin release of the thawed islets and improved their insulin response to 16.7 mM glucose. Thawed pancreatic fragments subjected to these additional procedures, transplanted into the peritoneal cavity of streptozotocin-induced diabetic rats, reduced their hyperglycemia significantly. The thawed fragments and islets did not differ from their corresponding non-frozen controls in 3H-leucine incorporation. The maintenance of tissue function was not satisfactory. However, our observations indicate that culturing pancreatic tissue before freezing and after thawing and the stepwise dilution of the cryoprotective agent reduce the damage induced by freezing the tissue.
To characterize insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in terms of the complement system, some components of the system as well as the related substances and indices were studied. CH50, C3, C4 and C3bINA significantly increased in both IDDM and NIDDM compared with non-diabetic healthy controls. ACH50 was also elevated in NIDDM, whereas it was similar in IDDM and controls. Besides, the serum concentration of C3d, a breakdown product of C3, was higher in IDDM than in NIDDM and healthy controls, but that in NIDDM did not differ significantly from the control. B1Hg1 was not different among IDDM, NIDDM and non-diabetic controls. These observations suggested that there is a high level of complements in both types of diabetes mellitus, but the complement activation seems to be much enhanced in IDDM compared with NIDDM.
After administration of N-methyl-N'-nitro-N-nitrosoguanidine for 15 weeks, the effects of bilateral, anterior and posterior vagotomy on the incidence, number and location of gastric adenocarcinomas, gastric acid secretion and cell proliferation of the gastric mucosa were investigated in inbred Wistar rats. Bilateral or anterior vagotomy, but not posterior vagotomy, significantly increased the incidence and number of adenocarcinomas at experimental week 52. In sham-operated control rats and rats subjected to bilateral vagotomy, there was no significant difference between the incidence or number of gastric tumors in the anterior and posterior walls. After anterior and posterior vagal denervation, however, there were significantly more gastric cancers on the denervated side than on the other. Bilateral and unilateral vagotomy resulted in significantly reduced gastric acid secretion by experimental weeks 25 and 52. Bilateral vagotomy significantly increased the labelling indices of both the fundic and antral mucosa at both times, but did not cause any significant difference between those of the anterior and posterior wall. Anterior or posterior vagotomy resulted in a significant increase in the labelling indices of both the fundic and antral mucosa on the denervated side. These findings indicate that the vagal nerve exerts a trophic action on the gastric mucosa, and that the promoting effect of vagotomy on gastric carcinogenesis may be related to its effect in increasing proliferation of cells in the antral mucosa.
We assessed peripheral and autonomic nerve function in 27 diabetics. Ten had malnutrition-related diabetes mellitus (MRDM), eight insulin-dependent diabetes mellitus (IDDM), and nine non-insulin-dependent diabetes mellitus (NIDDM). The frequency of peripheral neuropathy was 70, 78 and 13% in MRDM, NIDDM and IDDM respectively. Furthermore, the frequency of abnormality in cardiac beat-to-beat variation was 50 and 38% in MRDM and IDDM respectively, whereas our NIDDM patients did not show this abnormality. The patients with MRDM thus revealed a high frequency of not only peripheral but also autonomic neuropathy. Autonomic dysfunction appears to be a new characteristic of MRDM, not mentioned by the WHO study group.
A relation of the complement system to the development of complications in non-insulin-dependent diabetes mellitus (NIDDM) was evaluated by measuring some components of the complement system. CH50, C3, C4 and C3bINA were significantly elevated in subjects with NIDDM as compared with healthy non-diabetic controls. However, CH50 and C3 did not differ between diabetics with and without complications. C4 was higher in diabetics with retinopathy as well as with retinopathy and neuropathy than in diabetics without these complications. ACH50, beta 1Hg1 and C3d were similar in subjects with NIDDM and non-diabetics, and not associated with complications of NIDDM. C3d/C3 in NIDDM without complications was lower than in healthy subjects, but did not significantly differ between the types of complications. These results suggest that the high level of complements in NIDDM might be due to enhanced production of complements and the development of diabetic complications would be related to the elevated level of complements.
The effect of tetragastrin on the induction of intestinal metaplasia by intragastric administration of 5% NaOH solution was investigated in Wistar rats. The prolonged administration of tetragastrin in depot form from 1 week after NaOH treatment resulted in a significant increase in basal gastric acid secretion and a significant reduction in the incidence and number of intestinal metaplasia in experiment week 35. A histologic examination showed goblet cell metaplasia and intestinal metaplasia without Paneth cells in rats treated only with olive oil. Only goblet cell metaplasia was found in rats treated with tetragastrin. These results show that the prolonged administration of tetragastrin to rats after NaOH treatment increases gastric acid secretion and suppresses the induction of intestinal metaplasia.
The distribution of gamma-aminobutyric acid (GABA) containing neurons in the rat pituitary gland and related hypothalamic areas was immunohistochemically investigated using antibodies raised against GABA conjugated to bovine serum albumin by glutaraldehyde. A dense network of GABA-like immunoreactive fine varicose nerve fibers was observed within the posterior and intermediate lobes of the pituitary gland, surrounding endocrine cells and capillaries, but not in the anterior lobe. In the pituitary stalk, the dense varicose fibers ran along the anterior wall of the posterior lobe into the posterior and intermediate lobes. A small number of GABA-like immunoreactive cell bodies were evident in the intermediate lobe. GABA-like immunoreactive fibers occurred at low to high density in most parts of the hypothalamus. GABA-like immunoreactive neurons were observed in some regions related to the pituitary gland (such as periventricular nucleus, paraventricular nucleus, arcuate nucleus and accessory magnocellular nucleus). These results provide morphological evidence for the presence of GABAergic neurons in the rat hypothalamo-pituitary system.
Freezing has been shown to damage pancreatic islets and to disrupt their insulin release, probably because of intracellular ice formation. We compared frozen islets with fresh ones and with others stored at temperatures above freezing from a standpoint of insulin release response to glucose and transplantation. Group A islets, isolated from rats and immersed in 10% dimethyl sulfoxide in RPMI 1640, were stored at -2 degrees C, and group B islets at -196 degrees C, for 7 days. As for group B, the islets were cooled at 1 degree C/min from room temperature to -40 degrees C, subsequently at 3 degrees C/min to -80 degrees C and then put into liquid nitrogen to be rapidly frozen to -196 degrees C. The control islets were fresh. In vitro, basal release at 3.3 mM glucose was similar in group A to that in the controls, but was higher in group B than group A. Stimulated release against 16.7 mM glucose was lower in group A than group B. However, insulin responsiveness, i.e., the ratio of insulin release at 16.7 mM glucose to that at 3.3 mM glucose, was lost in group B. Freezing also caused damage to the group B cells visible under the light and electron microscopes, while group A islets were largely intact. In vivo, after 600 islets were transplanted into streptozotocin-induced diabetic rats, group A was better able to lower fasting blood glucose than was group B, and remained so for 4 weeks. Above sub-zero preservation in the non-frozen state thus seems adequate for the short-term storage for 7 days.
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Growth of 3T3-L1 cells was inhibited by 10(-10)-10(-7)M of 1 alpha,25-dihydroxy vitamin D3 [1 alpha,25(OH)2D3] in a dose- and time-dependent manner. The potency of 1 alpha,25(OH)2D3 in inducing differentiation was low, since 3T3-L1 cells cultured with 1 alpha,25(OH)2D3 did not become mature adipocyte-like cells but were changed to slightly rounded cells containing small droplet-like substances in the cytoplasm and glycerophosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+2-oxidoreductase, EC 1.1.1.8), the marker enzyme of differentiation to adipocyte, did not increase. These results together with the natural occurrence of this vitamin indicate that 1 alpha,25(OH)2D3 may play an important role in the cell growth and differentiation besides such known action as intestinal calcium transport and bone mineral mobilization.