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Biomedical subjects

S Fukumoto

Publications and source records attributed to S Fukumoto.

At least 163 records · Page 9Linked to original sources
PubMed1991

Transforming growth factor beta inhibits plasminogen activator (PA) activity and stimulates production of urokinase-type PA, PA inhibitor-1 mRNA, and protein in rat osteoblast-like cells.

Transforming growth factor beta (TGF beta) treatment of rat osteoblast-rich calvarial cells or of the clonal osteogenic sarcoma cells, UMR 106-01, resulted in dose-dependent inhibition of plasminogen activator (PA) activity, and increased production of 3.2 kb mRNA and protein for PA inhibitor -1 (PAI-1). Although tissue-type PA (tPA) protein was not measured, TGF beta did not influence production of mRNA for tPA. Production of 2.3 kb mRNA for urokinase-type PA (uPA) was also increased by TGF beta in a dose-dependent manner. The effects of TGF beta on synthesis of mRNA for PAI-1 and uPA were maintained when protein synthesis was inhibited, and were abolished by inhibition of RNA synthesis. Although uPA had not been detected previously as a product of rat osteoblasts, treatment of lysates of osteoblast-like cells with plasmin yielded a band of PA activity on reverse fibrin autography, corresponding to a low Mr form of uPA. Untreated conditioned media from normal osteoblasts or UMR 106-01 cells contained no significant TGF beta activity, but activity could be detected in acidified medium. Treatment of conditioned media with plasmin resulted in activation of approximately 50% of the TGF beta detectable in acidified media. The results identify several effects of TGF beta on the PA-PA inhibitor system in osteoblasts. Net regulation of tPA activity through the stimulatory actions of several calciotropic hormones and the promotion of PAI-1 formation by TGF beta could determine the amount of osteoblast-derived TGF beta activated locally in bone. Stimulation of osteoblast production of mRNA for uPA could reflect effects on the synthesis of sc-uPA, a precursor for the active form of the enzyme.

Animals↗
PubMed1991

Distinctive effects of three different modes of exercise on oxygen uptake, heart rate and blood lactate and pyruvate.

We intended to investigate the effects of different modes of exercise on oxygen uptake (VO2), the heart rate and the levels of lactate and pyruvate in venous blood. For this, untrained male subjects performed three modes of exercise with a treadmill (TR), a bicycle ergometer (UP) and a supine leg ergometer (SU). The percentage of maximal oxygen uptake (% VO2max) and VO2/weight for TR were significantly higher than those for UP or SU at lactate levels of 2, 3 and 4 mmol/l. The heart rate was also higher for TR than for SU at these lactate levels. The correlations of blood lactate with % VO2max, VO2/weight and the heart rate were significant for TR and SU, but not for UP. Blood lactate levels were lower for TR than for SU or UP at 60, 70, 80% VO2max, whereas the values for UP were lower than those for SU only at 60% VO2max. Blood pyruvate levels were always lower for TR than for SU. The ratios of lactate/pyruvate differed for TR and SU only at 60% VO2max. For a given mode of exercise, blood lactate and the ratio of lactate/pyruvate increased with an increase in % VO2max, but those of pyruvate did not. These results reveal that the relationships between any two of lactate, pyruvate, VO2 and the heart rate are different at different modes of exercise, and that blood lactate depends on adaptation of muscles to a mode of exercise rather than on the quantity of muscles mobilized.

Adult↗
PubMed1991

Scanning electron microscopic observations of three-dimensional structure of the rat pancreatic duct.

To understand the fine, three-dimensional structure of the pancreatic duct, we made corrosion casts of rat pancreatic ducts and obtained biological specimens of rat pancreatic tissues for scanning electron microscopic observation. We observed the corrosion casts and the inner surfaces of the pancreatic duct specimens, using scanning electron microscopy. A comparative study between casts and specimens demonstrated the exactitude of our corrosion casts. These findings revealed the following facts: 1) The pancreatic ductal system had an almost tree-like shape, but parts of the intercalated ducts anastomosed with each other; 2) Intralobular ducts branched almost at a right angle from the interlobular ducts. Intercalated ducts, which branched off from the intralobular ducts, wound and forked into two branches, without any decrease in thickness. The intercellular secretory canaliculi extended from the central lumina, running straight through the center of the acini, close to the cell bases; 3) In pancreatic ducts, every lumen was covered with microvilli. The diameters of these microvilli were uniform (about 0.1 micron), but the heights were variable, even within a given pancreatic duct.

Animals↗
PubMed1991

Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production.

Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome.

Adrenal Gland Neoplasms↗
PubMed1991

Electron microscopic studies on duck hepatitis B virus particles in hepatocytes and sequential changes in various patterns of infection.

To investigate the critical factors involved in the elimination of the duck hepatitis B virus (DHBV) in acute infection, the sequential changes in the number of DHBV particles in hepatocytes were studied electron microscopically in ducks experimentally infected by DHBV. Twenty Japanese white Peking ducks were infected with DHBV on the day of hatching, and on the 7th day and 14th day after hatching. Inoculation of DHBV on the day of hatching, and on the 7th and 14th day after hatching resulted in persistent viremia, transient viremia and no viremia, respectively in ducks as tested by spot hybridization assay. The number of DHBV particles in the liver correlated well with the amount of serum DHBV-DNA, DHBV particles decreased in hepatocytes without any interaction of inflammatory cells over the observation period, and the number of particles was not associated with the degree of hepatic inflammation. From these results, the elimination of the virus was thought to be induced by a reduction of viral replication in the hepatocytes and not by destruction of their host cells. There must be an age-dependent factor which strongly suppresses the viral replication.

Animals↗
PubMed1991

[Cell kinetic study on the healing process of indomethacin-induced gastric mucosal lesion of rats].

In healing process of indomethacin (IND)-induced gastric mucosal lesion of rats, cell kinetics in the cells from margin of mucosal lesion, background mucosa and pyloric gland mucosa were investigated with histochemistry using bromodeoxyuridine. Results obtained were as follows; 1) In marginal cells of mucosal lesion, cell number of s-phase expressing the cell renewal abruptly increased 6 hours after IND injection, showed maximal value at 24 hours and kept higher value even at 72 hours, when the lesions were in scar stage. 2) In background mucosal cells, the cell number of s-phase showed higher value at 12 hours after IND injection, although statistically not significant, and significantly lower value at 24 and 48 hours after IND injection. 3) Some s-phase cells were observed in the surface epithelial cells covering the mucosal defect. 4) In pyloric gland mucosal cells, there was no remarkable change in cell number of s-phase during the experimental period. It was concluded that in healing process of acute gastric mucosal lesion, there was a time lag between the macroscopic observation and cell kinetics in normalization of s-phase cell number.

Animals↗
PubMed1990

Epidemiology of abomasal nematodes of dairy cattle in Hokkaido, northern Japan.

The prevalence and intensity of infection with abomasal nematodiasis was studied in dairy cattle of Hokkaido, northern Japan, for successive two years. During the period of March in 1985 to September in 1987, a total number of 393 abomasa of Holstein-Friesian cows was examined for nematode parasites. Nematodes were detected from 75% of the cows. The prevalence of nematode species detected was Ostertagia ostertagi 250 (63.6%), Mecistocirrus digitatus 181 (46.1%), Trichostrongylus axei 85 (21.6%) and Haemonchus sp. 1 (0.3%). The prevalence and population composition of each growth stage varied seasonally in O. ostertagi and M. digitatus. The large percentage of arrested larvae, early L4 O. ostertagi and immature L5 M. digitatus, detected during the mid-winter and the increasing percentage of matured adult populations of both species in early spring revealed the occurrence of the autumn associated arrested development (hypobiosis) phenomenon in bovine abomasum nematodes of Japan.

Abomasum↗
PubMed1989

Parathyroid hormone-related protein in adult T-cell leukemia-lymphoma.

OBJECTIVE: To determine whether parathyroid hormone-related protein is synthesized and secreted by the tumor cells of patients with adult T-cell leukemia-lymphoma. DESIGN AND PATIENTS: Convenience sample of three patients with adult T-cell leukemia-lymphoma. Two patients developed hypercalcemia, and one patient was normocalcemic. SETTING: Inpatient facilities at two university-affiliated medical centers. INTERVENTION: All patients had a lymph node biopsy. In addition, samples of ascitic or pleural fluid, or both, were obtained from these patients. MEASUREMENTS AND RESULTS: Using RNA blot analysis, we showed that parathyroid hormone-related protein (PTHrP) messenger RNAs (mRNAs) were constitutively expressed in the tumor cells from all patients. Cyclic adenosine monophosphate (cAMP) production-stimulating activity, assessed using osteoblast-like UMR106 cells, was demonstrated in the pleural and ascitic fluids from the two patients who developed hypercalcemia. The elution profiles of the cAMP production-stimulating activity in the ascitic fluid extracts were very similar to those of the tumor extracts from hypercalcemic nude rats that had been implanted with a human cancer tumor. CONCLUSIONS: Parathyroid hormone-related protein is produced by tumor cells in adult T-cell leukemia-lymphoma, which may be an important factor in the development of hypercalcemia in the patients with this disease. However, the development of hypercalcemia may depend on other factors such as the number of tumor cells, access of the protein into systemic circulation, and the presence of some additional substances.

Adult↗
PubMed1989

Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes.

Because many patients with adult T-cell leukemia/lymphoma (ATLL) develop hypercalcemia with similar characteristics to those of humoral hypercalcemia of malignancy (HHM) (Arch. Intern. Med., 148: 921-925, 1988), we investigated if ATLL cells produce parathyroid hormone (PTH)-like activity. Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria. Furthermore, the stimulation of cyclic AMP production by conditioned medium of MT-2 cells was inhibited by human PTH(3-34), indicating that MT-2 cells secrete PTH-like activity. The PTH-like activity from MT-2 cells was chromatographically indistinguishable from the one extracted from a solid tumor causing HHM. The present results along with our previous observation that MT-2 cells constitutively express mRNA for PTH-related protein (Biochem. Biophys. Res. Commun., 154: 1182-1188, 1988) demonstrate that a PTH-like activity is synthesized and secreted by these cells, and are consistent with the hypothesis that elaboration of PTH-like activity by ATLL cells may be the mechanism by which hypercalcemia develops in ATLL patients as well as in solid cancer patients with HHM. However, these results do not rule out the possibility that other factors such as interleukin 1 are also involved and may act in concert with PTH-like activity in the development of hypercalcemia in ATLL.

Adult↗
PubMed1989

Pancreatic biopsy under visual control in conjunction with laparoscopy for diagnosis of pancreatic cancer.

Two cases of histologically confirmed pancreatic cancer are reported. Histological diagnosis was obtained after pancreatic biopsy was carried out under visual control in conjunction with laparoscopy using pancreatic biopsy forceps designed by us. In Case 1, localized swelling of the pancreas was observed on abdominal ultrasonography (US) and computer tomography (CT) scan, and interruption of the main pancreatic duct was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP). In Case 2, a pancreatic tumor was detected by abdominal US and CT scan, but ERCP findings were only those of chronic pancreatitis.

Adenocarcinoma↗
PubMed1989

Laparoscopic observation of hepatic lobe atrophy.

From the standpoint of diagnostic laparoscopy, the frequency and etiological aspect of atrophy of a lobe of the liver was studied. The frequency of hepatic lobe atrophy was 5.3% among 1,208 laparoscopy cases at our department. Lobe atrophy of the liver can be seen not only in congenital anomaly, atrophic cirrhosis and malformation, as described in the OMED database of digestive endoscopy, but also in some other kinds of liver diseases including chronic hepatitis, idiopathic portal hypertension, primary biliary cirrhosis, drug-induced liver injury, scarred liver, autoimmune hepatitis and also in malignancies of other visceral organs. The disorders most frequently associated with hepatic lobe atrophy were idiopathic portal hypertension, and scarred liver, primary biliary cirrhosis, etc.

Atrophy↗
PubMed1989

Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3.

Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level. It is suggested that 24,25-(OH)2D3 plays a role in modifying serum 1,25-(OH)2D3 concentrations by affecting the metabolism of 1,25-(OH)2D3 and may have a therapeutic values in the treatment of hypercalcemia or hypercalciuria caused by 1,25-(OH)2D3 excess.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Suppression of serum 1,25-dihydroxyvitamin D in humoral hypercalcemia of malignancy is caused by elaboration of a factor that inhibits renal 1,25-dihydroxyvitamin D3 production.

Although many patients with humoral hypercalcemia of malignancy exhibit reduced serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels, N-terminal fragments of recently identified PTH-related protein as well as PTH itself elevate serum 1,25-(OH)2D concentrations. In the present study, the effect of tumor extracts from human tumor-implanted hypercalcemic nude rat models with high and low serum 1,25-(OH)2D on renal 1,25-(OH)2D3 production was examined using rat kidney cells in culture. Whereas tumors from rats with high serum 1,25-(OH)2D levels (OCC rats) contained only a single peak of cAMP production-stimulating activity (CPSA) in osteogenic sarcoma cells on reverse phase HPLC, tumor extracts from rats with low serum 1,25-(OH)2D levels (UCC rats) contained at least two peaks of CPSA. The main peak (peak A) was estimated to be approximately 17K by gel permeation chromatography, which was the same as the molecular size of the hitherto identified PTH-related protein, and a minor peak of CPSA (peak B) was estimated to be about 25K. When peak A or crude extracts of OCC tumors as well as human PTH-(1-34) were added to primary cultures of rat kidney cells, the production of 1,25-(OH)2D3 was significantly stimulated. In contrast, although peak B or crude UCC tumor extracts had no effect on 1,25-(OH)2D3 production in themselves, when they were added together with peak A or human PTH-(1-34) the stimulation of 1,25-(OH)2D3 production was almost completely inhibited. Both peak A and peak B enhanced cAMP production in cultured kidney cells, and the cAMP production by peak A was not affected by peak B. These results are consistent with the possibility that elaboration of an additional factor from tumor cells may be the mechanism by which serum 1,25-(OH)2D levels are suppressed in patients with humoral hypercalcemia of malignancy. The nature as well as the mechanism of action of this factor remain to be elucidated.

Animals↗
PubMed1988

Expression of parathyroid hormone-related protein in a human T cell lymphotrophic virus type I-infected T cell line.

We analyzed human T cell lymphotrophic virus type I (HTLV-I)-infected T cells for the presence of mRNA coding for parathyroid hormone-related protein (PTHrP) by Northern blotting using synthetic DNA probes. We report here that PTHrP mRNAs were detected in a HTLV-I-infected T cell line, MT-2, but not in uninfected T cell or B cell lines, and that PTH-like bioactivity was detected only in the conditioned medium of MT-2 cells. Our study suggests that the pathophysiology of hypercalcemia in patients with adult T cell leukemia/lymphoma may resemble that which occurs with solid tumors.

Cell Line↗