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Biomedical subjects

K Takehara

Publications and source records attributed to K Takehara.

At least 127 records · Page 7Linked to original sources
PubMed1997

Circulating intercellular adhesion molecule-1 in the sera of patients with systemic sclerosis: enhancement by inflammatory cytokines.

We measured serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) in patients with systemic sclerosis (SSc) and normal controls. The levels of cICAM-1 were determined by sandwich enzyme-linked immunosorbent assay in sera from 88 patients with SSc and in 20 healthy controls. In addition, these levels were examined in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and dermal fibroblasts from 10 patients with SSc and 10 healthy control subjects. Serum levels of cICAM-1 were significantly higher in patients with SSc than in healthy controls. Serum cICAM-1 levels were significantly higher in patients with diffuse cutaneous SSc (dcSSc) than in patients with limited cutaneous SSc (lcSSc). These serum levels were correlated with the presence of contracture of phalanges, pulmonary fibrosis, joint involvement and increased erythrocyte sedimentation rate. The release of cICAM-1 was significantly increased in the supernatants of cultured PBMC from patients with SSc. Moreover, inflammatory cytokines (interferon-gamma, interleukin-1 and tumor necrosis factor-alpha) enhanced the release of cICAM-1 in vitro in SSc cells. These findings suggest that cICAM-1 may be involved in immune reactions in this disease.

Cells, Cultured↗
PubMed1997

Simultaneous measurement of serum 5-S-cysteinyldopa, circulating intercellular adhesion molecule-1 and soluble interleukin-2 receptor levels in Japanese patients with malignant melanoma.

Serum 5-S-cysteinyl dopa (5-S-CD), circulating intercellular adhesion molecule-1 (cICAM-1) and soluble interleukin-2 receptor (sIL-2R) have each been reported as useful markers for melanoma progression. To assess the clinical relevance of these three markers, we simultaneously assayed their serum levels in 30 Japanese melanoma patients. Pre-surgical serum levels of 5-S-CD, cICAM-1 and sIL-2R were elevated in six, 13 and five patients respectively. These abnormal values returned to normal after curative surgery in most of the patients, suggesting a direct relationship to the presence of the primary tumour. Pre-surgical values of these three markers, either individually or in combination, did not predict the development of subsequent metastases. The sequential measurements of the three markers in eight patients who had relapse after surgery showed that serum 5-S-CD is the most useful marker for disease progression, although it is dependent on the melanin-producing ability of individual recurrent tumours. sIL-2R seemed to reflect in vivo activation of the host immune system and was a good indicator for predicting occult metastasis in selected cases. Circulating ICAM-1 levels were less relevant to the clinical disease course in our cases, although they tended to increase strikingly after liver metastasis. Our results in this limited number of cases show that the significance of the three markers varied with the individual and suggest that the simultaneous measurement of these markers may facilitate the early detection of metastases and proper therapeutic intervention.

Adult↗
PubMed1997

Immunohistochemical analysis of platelet-derived growth factor and its receptors in fibrohistiocytic tumors.

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of fibroblasts, although the role of PDGF and its receptors in the development of fibrohistiocytic tumors has not been clarified. In this study, we investigated this role by immunohistochemically staining PDGF and PDGF beta-receptors in paraffin-embedded dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH) tissue. We also immunohistochemically investigated the relationship between PDGF beta-receptors and CD34, which is a known immunohistochemical marker for DFSP. Immunohistochemical studies using anti-PDGF-AA or BB antibodies showed that PDGF-AA and BB was found in 20 to 40% of the tumor cells in DF, DFSP, and MFH. No definite relationship for each tumor type was found. The expression of PDGF beta-receptors in DFSP and that of MFH tissue was significantly greater in comparison to DF and scar tissue. The expression of CD34 and PDGF beta-receptors in DFSP was observed in identical areas. These findings suggest that autocrine or paracrine growth stimulation, through PDGF beta-receptors, is related to the tumorous proliferation of fibrohistiocytic tumors, and the expression of PDGF beta-receptors might play a role in the proliferation of CD34 positive tumor cells.

Antigens, CD34↗
PubMed1997

PACAPs stimulate duodenal bicarbonate secretion at PACAP receptors in the rat.

We investigated the effects of pituitary adenylate cyclase-activating polypeptides (PACAPs) on gastroduodenal HCO(3)- secretion in anesthetized rats and characterized their effects by comparison with the effects of vasoactive intestinal polypeptide (VIP). Under urethan anesthesia, a rat proximal duodenal loop or a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) was perfused with saline, and HCO(3)- secretion was measured at pH 7.0 using a pH-stat method and by addition of 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO(3)- secretion in a dose-dependent manner in the duodenum, but not in the stomach, although this peptide had no effect on duodenal HCO(3)- secretion after intracisternal administration. The duodenal HCO(3)- stimulatory action was similarly observed after intravenous administration of PACAP-38 and VIP, and the potency of action was in the following order: PACAP-27 > PACAP-38 = VIP. The duodenal HCO(3)- stimulatory action of PACAP-27 was potentiated by pretreatment with 3-isobutyl-1-methylxanthine, similar to that of prostaglandin E2, and was significantly attenuated by PACAP-(6--27) (PACAP antagonist) or Ac-Tyr1,D-Phe2-VIP (VIP antagonist) but was not affected by bilateral vagotomy or prior administration of atropine, verapamil, and indomethacin. Forskolin, the stimulator of adenylate cyclase, also increased HCO(3)- secretion in the duodenum, but not in the stomach. These results suggest that 1) PACAP is a potent stimulator of HCO(3)- secretion in the duodenum, but not in the stomach, and may be involved in the peripheral regulation of duodenal HCO(3)- secretion, 2) this action is mediated by adenosine 3',5'-cyclic monophosphate, probably through PACAP and VIP receptors, and 3) adenosine 3',5'-cyclic monophosphate is a mediator in duodenal, but not in gastric, HCO(3)- secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Role of nitric oxide in mucosal blood flow response and the healing of HCl-induced lesions in the rat stomach.

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase.

Animals↗
PubMed1997

Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis.

OBJECTIVE: To determine whether serum interleukin 4 (IL-4), IL-10, and IL-13 levels in patients with systemic sclerosis (SSc) are elevated and whether they correlate with the clinical or serologic features of this disease. METHODS: Serum samples from patients with limited cutaneous SSc (ISSc) (n = 45), diffuse cutaneous SSc (dSSc) (n = 28), and control subjects (n = 30) were examined by ELISA. RESULTS: Serum IL-4 and IL-13 levels were significantly higher in patients with ISSc and dSSc than in the controls. Serum IL-10 levels were significantly higher in the patients with dSSc compared with controls. Elevated IL-10 levels were detected frequently in patients with arthralgia. Serum IL-13 levels correlated with erythrocyte sedimentation rates and C-reactive protein levels in patients. CONCLUSION: We suggest that IL-4, IL-10, and IL-13 may be some of the cytokines that contribute to the disease process, and that IL-13 may be a serologic indicator of systemic inflammation in patients with SSc.

Adolescent↗
PubMed1997

Elevated serum tumor necrosis factor-alpha levels in patients with systemic sclerosis: association with pulmonary fibrosis.

OBJECTIVE: To determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated, and whether they correlate with clinical features in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (ISSc) (n = 51), diffuse cutaneous SSc (dSSc) (n = 30), and control subjects (n = 30) were examined by ELISA. RESULTS: Serum TNF-alpha levels were elevated in patients with ISSc and dSSc and correlated with the presence of pulmonary fibrosis and with the decreased vital capacity of the patients. CONCLUSION: Serum TNF-alpha may be one of the cytokines that contribute to the disease process, especially to pulmonary fibrosis in patients with SSc.

Adolescent↗
PubMed1997

Impaired healing of gastric lesions in streptozotocin-induced diabetic rats: effect of basic fibroblast growth factor.

We examined the influence of diabetes on the healing of HCI-induced gastric lesions and the healing promoting effect of basic fibroblast growth factor (bFGF) on these lesions under diabetic conditions induced in rats by streptozotocin (70 mg/kg, i.p.). The experiments were performed using 2-wk streptozocin-diabetic rats with blood glucose levels of >300 mg/dl. After 18 hr fasting, these animals were given 1 ml of 0.6 N HCl by gavage, and 1 hr later they were fed normally before being killed on various days after HCI treatment. Recombinant human basic fibroblast growth factor (acid resistant recombinant human basic fibroblast growth factor mutein CS-23: 10 to 1000 ng/kg x 2, p.o.) or insulin (4 U/rat x 1, s.c.) was given 5 days after HCl treatment. Gastric lesions induced by HCI healed to quiescent state within 5 days both macro- and microscopically. Diabetic conditions did not affect the development of HCI-induced gastric lesions but significantly delayed the healing of these lesions. Daily administration of insulin returned high blood glucose levels to within normal ranges (120-140 mg/dl) and significantly antagonized the delayed healing of these lesions. The delayed healing in diabetic rats was also significantly promoted by recombinant human basic fibroblast growth factor (>300 ng/kg x 2) without any effect on blood glucose level. In normal rats, the mucosal levels of bFGF increased significantly in response to gastric injury at 3 days after HCI treatment. The mucosal bFGF levels in streptozotocin-diabetic rats were significantly lower under basal conditions before HCI treatment and did not increase after injury, yet such dysregulation of bFGF production was partially restored by insulin treatment. rhbFGF even at 1000 ng/kg had no effect on gastric acid secretion in either normal or streptozotocin-diabetic rats. These results suggest that diabetic conditions have deleterious influences on the healing of acute gastric lesions in both an insulin- and bFGF-sensitive manner, and that the administration of exogenous bFGF antagonizes the delayed healing of gastric lesions observed in diabetic animals.

Animals↗
PubMed1996

Elevated soluble CD23 levels in the sera from patients with localized scleroderma.

Soluble CD23 (sCD23) is closely related to B-cell activation and elevated serum levels of sCD23 have been reported in several autoimmune disorders. This study investigated the serum levels of sCD23 and determined the correlation of sCD23 with other immunologic abnormalities and clinical features in localized scleroderma. We examined 49 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphoea, 22 with linear scleroderma, and 12 with morphoea. The serum levels of sCD23 were significantly elevated in patients with localized scleroderma, compared with those in healthy individuals. Of the three subgroups of localized scleroderma, patients with generalized morphoea had the highest levels of serum sCD23. The frequency of IgM antihistone antibody (AHA) and IgM rheumatoid factor (RF), the number of linear lesions, and the frequency of muscle involvement were significantly higher in patients with elevated sCD23 levels than in those with normal levels of sCD23. A significant correlation between the serum sCD23 level and the number of involved areas of the body was observed. Our data suggest that the activation of virgin B cells, which is reflected by elevated sCD23 levels, is closely associated with the production of IgM autoantibodies in localized scleroderma and furthermore that the serum levels of sCD23 are a new serological indicator of the severity of localized scleroderma.

Adolescent↗
PubMed1996

Soluble CD4 and CD8 in serum from patients with localized scleroderma.

Localized scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with localized scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in localized scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in localized scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.

Adult↗
PubMed1996

Detection of Goose parvovirus genome by polymerase chain reaction: distribution of Goose parvovirus in Muscovy ducklings.

A portion of the Goose parvovirus (GPV) genome DNA was cloned, sequenced, and primers for polymerase chain reaction (PCR) were prepared. The specificity of the clone was checked by Southern blot hybridization to GPV genome and by in situ hybridization with GPV infected cells. In Muscovy ducklings experimentally infected with the virulent GPV strain IH, the viral genome was detected by PCR on and after 2 days in many tissues including the brain. Using PCR, the primers also detected another GPV strain Ma isolated in Japan.

Animals↗
PubMed1996

Thrombocytopenia associated with hepatitis C viral infection.

BACKGROUND/AIMS: We investigated whether chronic hepatitis C infection is associated with thrombocytopenia. METHODS/RESULTS: Thrombocytopenia (<15 x 10(4) platelets/mu l) was diagnosed in 151 of 368 patients (41.0%) with chronic hepatitis C, a significantly higher proportion than that observed in patients with chronic hepatitis B (18.9%, p < 0.01). Elevated titers of platelet-associated immunoglobulin G were observed in 88.1% of patients with chronic hepatitis C and in 47.1% of patients with chronic hepatitis B. Platelet-associated immunoglobulin G titers were significantly higher in patients with chronic hepatitis C (87.3 +/- 10.1 ng/10(7) cells) vs. those with chronic hepatitis B (30.3 +/- 6.4) or the control subjects (p < 0.01). There was a significant negative correlation between platelet-associated immunoglobulin G titers and platelet counts in both chronic hepatitis C and B cases. Platelet-associated immunoglobulin G titers were significantly higher in patients with type C cirrhosis than in those with type B cirrhosis. Interestingly, HCV-RNA was detected by RT-PCR in the platelets from 11 of 14 patients with hepatitis C virus. CONCLUSIONS: These data indicate that chronic infection with hepatitis C virus may produce a significant autoimmune reaction to platelets, leading to thrombocytopenia.

Adult↗
PubMed1996

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy.

We describe a patient with subacute cutaneous lupus erythematosus, widespread pruritic papulosquamous plaques, and hypocomplementemia. Skin biopsy specimens revealed liquefaction degeneration and colloid bodies and dyskeratotic cells in basal and suprabasal layers. An immunofluorescence study revealed deposits of IgG, IgM, and C3 at the dermalepidermal junction in a bandlike pattern, and particulate IgG deposition in the basal and suprabasal layers. Treatment with prednisolone (15 mg/day), chloroquine phosphate (200 mg/ day), cyclosporine (5 mg/kg daily), and gold (10 mg/day) failed to reduce pruritic plaque formation, and pulse methylprednisolone therapy led to only a transient remission. Clinical exacerbations correlated with a decrease in complement levels. The disease was successfully controlled with dapsone (75 mg/day) and prednisolone (25 mg/day).

Adult↗
PubMed1996

Measurement of anticardiolipin antibodies by ELISA using beta 2-glycoprotein I (beta 2-GPI) in systemic sclerosis.

In order to determine the prevalence and clinical significance of beta 2-GPI-dependent anticardiolipin antibodies (beta 2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified beta 2-GPI. IgG isotype beta 2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of beta 2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of beta 2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype beta 2-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.

Antibodies, Anticardiolipin↗