Search PubMed⌕ Search

Biomedical subjects

S Fukumoto

Publications and source records attributed to S Fukumoto.

At least 127 records · Page 7Linked to original sources
PubMed1996

Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia.

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.

Adult↗
PubMed1996

Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type Ib.

To clarify the mechanism of resistance to PTH in patients with pseudohypoparathyroidism (PHP) type Ib, the complementary DNA (cDNA) for PTH/PTH-related protein (PTHrP) receptor was analyzed in skin fibroblasts from three patients with PHP Ib and compared with those from a patient with PHP Ia and a normal subject. We have divided the full coding region of PTH/PTHrP receptor cDNA into five parts and amplified the cDNA by reverse transcription-coupled PCR. There was no difference in the size of PCR products among these patients and the normal control. Single strand conformation polymorphism analysis of the PCR products also showed no aberrant bands in PHP Ib patients. Furthermore, no mutation in PTH/PTHrP receptor cDNA was found by direct sequencing of the PCR products from these patients. These results demonstrate that there is no mutation in PTH/PTHrP receptor cDNA from skin fibroblasts at least in the examined patients with PHP Ib. In addition, the expression of PTH/PTHrP receptor messenger ribonucleic acid was reduced in two patients but was increased in one patient with PHP Ib, suggesting that a reduction in PTH/PTHrP receptor expression cannot explain the resistance to PTH in all patients with PHP Ib. Elucidation of the pathogenesis of PHP Ib may require examination of tissue-specific abnormality in the PTH signal transduction system in the kidney.

Adolescent↗
PubMed1996

Stereoselective synthesis and thromboxane A2 (TXA2) receptor antagonistic activity of optically active phenol derivatives.

Enantiomers of four potent nonprostanoid thromboxane A2 (TXA2) receptor antagonists, (+/-)-7-(4-fluorophenyl)-7-(2-hydroxyphenyl)heptanoic acids (1-4), were synthesized stereoselectively by direct ortho-alkylation of phenols under modified Mitsunobu conditions. The reaction of 5 eq of phenols (6a-c) with 1 eq of (S)- or (R)-methyl 7-(4-fluorophenyl)-7-hydroxyheptanoate ((S)- or (R)-7) afforded ortho-alkylated phenol derivatives (6a-c) enantioselectively in 33 to 42% chemical yield and 90 to 93% ee. In these compounds, the (R)-enantiomers (1-4) exhibited potent TXA2 receptor antagonistic activity and the (S)-isomer (3) was much less active. In particular, compound (R)-3 strongly inhibited U-46619-induced human platelet aggregation (IC50 = 48 nM), and also showed a very potent inhibitory effect with a minimum effective dose (MED) of 0.3 mg/kg (p.o.) on U-46619-induced bronchoconstriction in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

A new host record of Camelostrongylus mentulatus (Nematoda; Trichostrongyloidea) from abomasum of a giraffe at a zoo in Japan.

Camelostrongylus mentulatus (Railliet et Henry, 1909) Orloff, 1933 (Nematoda; Trichostrongyloidea) was found from the abomasum of a three-year-old female cape giraffe, Giraffa camelopardalis giraffa, born and died in a zoo park in Yamaguchi prefecture, Japan. This is the new host record from Giraffidae and geographical distribution of C. mentulatus. Present case of C. mentulatus might be infected from other ruminants, e.g., camels, antelopes and goats, kept at a same paddock in the zoo. Risk of imported parasitic diseases by the zoo animals from outside of Japan is discussed.

Abomasum↗
PubMed1995

Antisense oligonucleotide inhibits the expression of procollagen type III gene in mouse fibroblasts.

The effects of transfection of phosphorothioate antisense oligonucleotides (ASOs) into BALB/c 3T3 mouse fibroblasts on procollagen type III production were examined. Immunohistochemistry and Western blots showed that the expression of procollagen type III decreased. Semi-quantitative reverse transcription polymerase chain reaction revealed that the expression of procollagen type III mRNA was inhibited. ASOs were effective for inhibiting procollagen type III production at the gene level, although the effect was transient.

3T3 Cells↗
PubMed1995

Two structurally distinct kappa B sequence motifs cooperatively control LPS-induced KC gene transcription in mouse macrophages.

The mouse KC gene is an alpha-chemokine gene whose transcription is induced in mononuclear phagocytes by LPS. DNA sequences necessary for transcriptional control of KC by LPS were identified in the region flanking the transcription start site. Transient transfection analysis in macrophages using deletion mutants of a 1.5-kb sequence placed in front of the chloramphenicol acetyl transferase (CAT) gene identified an LPS-responsive region between residues -104 and +30. This region contained two kappa B sequence motifs. The first motif (position -70 to -59, kappa beta 1) is highly conserved in all three human GRO genes and in the mouse macrophage inflammatory protein-2 (MIP-2) gene. The second kappa B motif (position -89 to -78, kappa B2) was conserved only between the mouse and the rat KC genes. Consistent with previous reports, the highly conserved kappa B site (kappa B1) was essential for LPS inducibility. Surprisingly, the distal kappa B site (kappa B2) was also necessary for optimal response; mutation of either kappa B site markedly reduced sensitivity to LPS in RAW264.7 cells and to TNF-alpha in NIH 3T3 fibroblasts. Although both kappa B1 and kappa B2 sequences were able to bind members of the Rel homology family, including NF kappa B1 (P50), RelA (65), and c-Rel, the kappa B1 site bound these factors with higher affinity and functioned more effectively than the kappa B2 site in a heterologous promoter. These findings demonstrate that transcriptional control of the KC gene requires cooperation between two kappa B sites and is thus distinct from that of the three human GRO genes and the mouse MIP-2 gene.

Animals↗
PubMed1995

Epidermal growth factor-stimulated parathyroid hormone-related protein expression involves increased gene transcription and mRNA stability.

Epidermal growth factor (EGF) produced rapid and striking effects on parathyroid hormone-related protein (PTHrP) gene expression in the immortalized human keratinocyte cell line, HaCaT. Steady-state levels of PTHrP mRNA and secreted PTHrP were increased 10-fold by maximally effective concentrations of EGF. EGF increased both PTHrP gene transcription and PTHrP mRNA stability. Nuclear run-on assays demonstrated a 4-fold increase in transcriptional rate in EGF-stimulated cells while transient transfection analysis indicated that the action of EGF on transcription involved both the GC-rich promoter, P2, and the downstream TATA promoter, P3, but apparently not the upstream TATA promoter, P1. In experiments where EGF treatment produced more stable PTHrP transcripts, the half-life of c-fos mRNA was unaltered, suggesting a relatively specific effect of EGF. Moreover, only those species of PTHrP mRNA containing two of the alternative 3' exons (exons VII and VIII) were stable, those containing exon IX were not. Reverse-transcription PCR demonstrated that EGF produced differential increases in the abundance of PTHrP mRNA species initiated by the three PTHrP promoters. The major effect was seen on the abundance of transcripts initiated by P1 and P2, with less marked regulation of P3-initiated transcripts. Thus EGF regulation of PTHrP gene expression in HaCaT cells is multifactorial and the combination of its actions at the 5' and 3' ends of the gene favours the accumulation of subpopulations of PTHrP mRNA containing exons I, VII and VIII.

Cell Line, Transformed↗
PubMed1995

Relationship between actions of transforming growth factor (TGF)-beta and cell surface expression of its receptors in clonal osteoblastic cells.

Various osteoblastic cell lines were examined for the relationship between the presence of cell-surface transforming growth factor (TGF)-beta receptors and the synthesis of matrix proteins with their responsiveness to TGF-beta. Treatment with TGF-beta 1 inhibited proliferation and stimulated proteoglycan and fibronectin synthesis in MC3T3-E1 and MG 63 cells. The major proteoglycans synthesized by these cells were decorin and biglycan, and TGF-beta 1 markedly stimulated the synthesis of decorin in MC3T3-E1 and of biglycan in MG 63 cells. SaOS 2 and UMR 106 cells synthesized barely detectable amounts of decorin or biglycan, and TGF-beta 1 did not stimulate the synthesis of these proteoglycans. In SaOS 2 cells, however, TGF-beta 1 enhanced fibronectin synthesis. TGF-beta 1 did not show any of these effects in UMR 106 cells. Receptor cross-linking studies revealed that only MC3T3-E1 and MG 63 cells had both types I and II signal-transducing receptors for TGF-beta in addition to betaglycan. SaOS 2 cells possessed type I but no type II receptor on the cell surface. In contrast, SaOS 2 as well as MC3T3-E1 and MG 63 cells expressed type II receptor mRNA by Northern blot analysis, and cell lysates contained type II receptor by Western blot analysis. Thus, it appears that type II receptor present in SaOS 2 cells is not able to bind TGF-beta 1 under these conditions. UMR 106 cells with no response to TGF-beta 1 had neither of the signal-transducing receptors by any of the analyses. These observations using clonal osteoblastic cell lines demonstrate that the ability of osteoblastic cells to synthesize bone matrix proteoglycans is associated with the responsiveness of these cells to TGF-beta 1, that the responsiveness of osteoblastic cells to TGF-beta 1 in cell proliferation and proteoglycan synthesis correlates with the presence of both types I and II receptors, and that the effect of TGF-beta 1 on fibronectin synthesis can develop with little binding of TGF-beta 1 to type II receptor if type I receptor is present. It is suggested that the combination of cell-surface receptors for TGF-beta determines the responsiveness of osteoblastic cells to TGF-beta and that changes in cell-surface TGF-beta receptors may play a role in the regulation of matrix protein synthesis and bone formation in osteoblasts.

Animals↗
PubMed1995

Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B.

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Fine structure of the cilia in the pancreatic duct of WBN/Kob rat.

We observed the cilia in pancreatic ducts (intraductal cilia) with scanning and transmission electron microscopy (SEM and TEM), using male WBN/Kob rats (W/K), which are the spontaneously developed chronic pancreatitis models with stasis of pancreatic juice, and male Wistar rats as control. By SEM observations, the lengths of cilia in interlobular ducts of 18-mo-old W/K were demonstrated to elongate markedly. By TEM observations in the controls, cross-sections of the intraductal cilia were demonstrated to present various numbers of microtubules (those with seven, eight, or nine microtubules accounted for 83.3% of all). There was no significant difference between W/K and controls in the number of microtubules in the cross-sections of intraductal cilia: the intraductal cilium core was provided with nine microtubules, which were different from the number of microtubules encountered within the cilium core of other ciliated cell (i.e., bronchial epithelium, and so forth), and their number in the cross-section of intraductal cilium decreased at a distal portion. Though some of their cross-sections revealed deformities of ciliary membranes and disarrangements of microtubular complex, there was no significant difference in their incidence between both rats. These findings suggest that the intraductal cilia have different functions from the ciliated cells' cilia, and W/K has the elongated intraductal cilia without internal structural change.

Animals↗
PubMed1995

X gene and precore region mutations in the hepatitis B virus genome in persons positive for antibody to hepatitis B e antigen: comparison between asymptomatic "healthy" carriers and patients with severe chronic active hepatitis.

Hepatitis B virus (HBV) carriers with antibody to hepatitis e antigen comprise asymptomatic carriers (ASCs), who have low replication levels of HBV, and patients with chronic active hepatitis (CAH), who have high levels of viral replication. To investigate whether defects in the X protein might be responsible for this difference in the level of viral replication, nucleotide sequences of X and precore gene regions in serum HBV were analyzed in 19 ASCs and 9 CAH patients. All patients had a point mutation creating a stop codon in the precore region. Seventeen ASCs (87.3%) had identical mutations consisting of 4 noncontiguous 1-bp deletions or an 8-bp deletion, both of which truncate the normal X protein, whereas no CAH patient had an X gene mutation (P < .001). Thus, deletion of the X protein might be responsible for the low levels of viral replication in ASCs.

Adult↗
PubMed1995

Scanning electron microscopic observation of pancreatic ducts in WBN/Kob rats.

To elucidate changes of pancreatic ducts in chronic pancreatitis, we observed pancreatic tissues with light microscopy and scanning electron microscopy, and corrosion casts of pancreatic ducts with scanning electron microscopy, in male WBN/Kob rats, considered a spontaneously occurring chronic pancreatitis model. At 3 months of age, hemorrhage and increased fibrosis were found in part of the pancreatic tail. After 3 months of age, pancreatic ductal lumina exhibited a winding form and inner surfaces showed long cilia and crater-like depressions. Fibrous tissues gradually extended into exocrine tissues and islets after 6 months of age. Most pancreatic ductal lumina developed a helical form with many deep depression at 14 months of age. It is suggested that increased pancreatic ductal pressure causes these findings.

Animals↗
PubMed1995

Gene expression of perforin and granzyme A in the liver in chronic hepatitis C: comparison with peripheral blood mononuclear cells.

Perforin and granzyme A are the major effectors of cytotoxic T cells in cell-mediated cytotoxicity. However, there has been no report on these effectors in chronic viral hepatitis. In the present study, the expression of perforin and granzyme A mRNA was investigated by the reverse transcription polymerase chain reaction method using liver biopsy specimens and peripheral mononuclear cells (PBMC) from 21 patients with chronic hepatitis C and 5 control cases. Perforin mRNA was detected only in the liver of chronic hepatitis patients but not in the control livers. Conversely, perforin mRNA was not expressed in PBMC of the patients with chronic hepatitis (P < 0.01). Granzyme A mRNA was detected both in the liver and PBMC of all the cases including control cases. These results indicated that the perforin is an important effector molecule in the hepatocyte lysis in chronic viral hepatitis C.

Base Sequence↗
PubMed1995

The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.

Adolescent↗
PubMed1995

Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats.

In vivo effects of basic fibroblast growth factor (bFGF) on bone formation was examined in rats. Daily systemic injections of 100 micrograms/kg bFGF for 7 days caused a marked stimulation of endosteal bone formation in both cortical and secondary cancellous bone areas. Histological examinations revealed that the sequence of responses to the injections of bFGF consisted of three phases: an early increase in the number of preosteoblastic cells over the osteoblastic cell layer (days 1-3), recruitment of osteoblasts from preosteoblastic cells (days 3-5), and an increase in new bone formation (days 5-7). These histological changes in the endosteum correlated closely with histomorphometrical parameters of bone formation, and the endosteal mineral apposition rate was almost unaffected during the initial 4 days but was markedly enhanced after this period. Immunohistochemical examinations using antitransforming growth factor (TGF)-beta 1 antibody demonstrated that immunostaining of preosteoblastic cells for TGF-beta already increased 1 day after bFGF treatment. Distribution of TGF-beta in osteoblasts and bone matrices began to increase on day 3, and all the osteoblasts and new bone matrices were intensively immuno-stained on day 7. These results demonstrate that systemic injections of bFGF in rats stimulate endosteal bone formation, and that the stimulation of bone formation is preceded by an initial increase in preosteoblastic cells with later recruitment of osteoblasts from these cells. Because the distribution of TGF-beta in the endosteal cells is increased by bFGF, the effect of bFGF may at least in part be mediated by TGF-beta. However, the precise mechanism of action of bFGF on bone formation remains to be clarified.

Animals↗