Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 19 recordsLinked to original sources

PubMed1995

IL-10 is involved in the protective effect of dibutyryl cyclic adenosine monophosphate on endotoxin-induced inflammatory liver injury.

The effects of exogenous cAMP, dibutyryl cAMP (DBcAMP) on LPS-induced liver injury were examined in mice made hypersensitive to LPS by treatment with i.v. injection of Propionibacterium acnes. In vivo administration of DBcAMP significantly protected P. acnes-treated mice from LPS-induced liver injury, including apoptosis of hepatocytes. DBcAMP significantly increased circulating IL-10 level in correlation with suppression of the TNF-alpha level after LPS challenge in P. acnes-treated mice. Treatment with anti-IL-10 mAb abrogated the protective effect of DBcAMP on LPS-induced liver injury. Similar to in vivo findings, addition to DBcAMP to in vitro culture of liver adherent cells from P. acnes-treated mice enhanced IL-10 synthesis after LPS stimulation. These results suggest that the increment in IL-10 production by liver adherent cells is involved in the protective effect of DBcAMP on LPS-induced inflammatory liver injury.

Animals↗

PubMed1995

Rat fibroblasts synthesize T-kininogen in response to cyclic-AMP, prostaglandin E2 and cytokines.

T-Kininogen is a plasma protein characterized as a kinin-precursor, a cysteine protease inhibitor and an acute phase protein in the rat. Rat fibroblasts prepared from meninges or embryos and 3Y1-B clone 1-6 cells, a rat fibroblast cell line, secreted T-kininogen. Incubating these cells with 1 mM Bt2cAMP or a combination with 1 microM dexamethasone resulted in a marked increase in T-kininogen secretion, as well as in the incorporation of radioactive methionine into newly synthesized T-kininogen. Secretion of T-kininogen by meningeal fibroblasts was stimulated by forskolin, prostaglandin E2, bradykinin and cytokines, such as tumor necrosis factor alpha, interleukin-1 alpha (IL-1) and IL-6. Expression of T-kininogen mRNA was demonstrated in meningeal fibroblasts by Northern blot hybridization using T-kininogen cDNA as a probe, and the expression was stimulated by Bt2cAMP, prostaglandin E2, and the cytokines described above. In contrast, expression of T-kininogen mRNA in rat hepatocytes was not altered by Bt2cAMP, prostaglandin E2, tumor necrosis factor and IL-1, whereas it was greatly stimulated by IL-6, suggesting the differential regulation of T-kininogen gene expression in fibroblasts and hepatocytes. These results demonstrated for the first time, that rat fibroblasts express the T-kininogen gene, and that the expression is regulated by inflammatory mediators and cytokines.

Adenylyl Cyclases↗

PubMed1995

Murine fibroblasts synthesize and secrete kininogen in response to cyclic-AMP, prostaglandin E2 and tumor necrosis factor.

Fibroblasts prepared from the meninges of newborn mice or from mouse embryos, as well as fibroblast L929 cells, secreted an immunoreactive material (ir-kininogen) against rabbit anti-mouse low-molecular-weight kininogen antibody in response to dibutyryl cAMP. Western blots using a bradykinin-directed monoclonal, as well as a polyclonal anti-mouse low-molecular-weight kininogen antibody, showed that ir-kininogen had a molecular weight of 80,000 and that it contained a kinin moiety. N-terminal amino acid sequence of the ir-kininogen was consistent with that of mouse L-kininogen. The ir-kininogen produced by fibroblasts released a kinin by incubating with trypsin and mouse submandibular gland kallikrein, and it was identified as bradykinin by means of high-performance liquid chromatography, indicating that mouse fibroblasts produce and secrete a kininogen. Forskolin, prostaglandin E2 and tumor necrosis factor alpha stimulated the production of ir-kininogen by meningeal fibroblasts, whereas neither dibutyryl cAMP nor these agents influenced kininogen production by mouse hepatocytes in primary cultures. These results demonstrated that fibroblasts are a source of kininogen in the mouse, and that it is regulated by the inflammatory mediators, prostaglandin E2 and tumor necrosis factor. Therefore locally produced kininogen is implicated in pathogenesis of inflammation.

Amino Acid Sequence↗

PubMed1995

Involvement of blood coagulation factor XIII in burn healing in the carbon tetrachloride-induced hepatic injury model in rats.

An involvement of blood coagulation factor XIII (FXIII) in healing of burns was examined in rats with the carbon tetrachloride (CCl4)-induced hepatic injury. The oral administration of 2 and 4 ml/kg CCl4 to rats every 4 days delayed healing of the burns induced on the back skin and decreased FXIII activity. These animals showed some hepatotoxic signs (increased glutamic-oxaloacetic and glutamic-pyruvic transaminases) and accelerated blood coagulation system (increased fibrino-peptide A and fibrin degradation product). The delay in the burn healing was shortened by repeated intravenous injections with normal human placenta-derived FXIII concentrate (Fibrogammin P; 120 U/body) every 4 days. There was a negative correlation between plasma FXIII activity at the end of experiment and the time required for wound healing. These findings suggest that reduction in FXIII activity may be one of the factors inducing delayed wound healing in the CCl4-induced hepatic injury rats.

Administration, Oral↗

PubMed1995

Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.

PURPOSE: The purpose of this study was the evaluation of various factors in the formulation of guidelines for treatment of early invasive colorectal cancer, in which malignant cells extend through the muscularis mucosa into the submucosa but do not deeply invade the muscularis propria. METHOD: A total of 182 patients were followed for at least five years or until death, with early invasive cancer diagnosed between 1982 and 1989. Patients were grouped according to the level of invasion, as follows: 64 patients with slight carcinoma invasion of the muscularis mucosa (200-300 microns; sm1), 82 with intermediate invasion (sm2), and 36 with carcinoma invasion extending to the inner surface of the muscularis propria (sm3). RESULT: The configuration, diameter, and histologic grade of adenocarcinoma and lymphovascular invasion were correlated with level of invasion. After endoscopic polypectomy or local resection, 4 patients showed local recurrence and 13 patients showed lymph node metastasis. None of these 17 patients had sm1 disease. The level of invasion, configuration, and location were significant risk factors for development of lymph node metastasis or local recurrence (P < 0.05), but lymphovascular invasion, histologic grade, and diameter were not risk factors. CONCLUSIONS: Preoperative assessment of the level of invasion using this classification, in which the submucosa is divided into three depths, may decrease the incidence of unnecessary surgery for sessile polyps. Assessment according to the level of invasion is useful in the formulation of appropriate guidelines for the treatment of early invasive cancer.

Adenocarcinoma↗

PubMed1995

Inducibility of endogenous tumor necrosis factor by tumor cells from colorectal tumor patients at Dukes stage C as a novel prognostic factor following curative operation.

PURPOSE: It is well known that tumor cells secrete endogenous tumor necrosis factor (en-TNF) as a cytokine when stimulated with lipopolysaccharide (LPS). We, therefore, analyzed the biologic role of en-TNF secreted by tumor cells themselves to learn the prognosis of patients and the susceptibility of tumors to biologic response modifiers in particular. METHODS: Patients with Dukes C colorectal tumors were studied after curative operation to determine the inducibility of en-TNF by their primary cultured cells in response to LPS. RESULTS: Irrespective of the known clinicopathologic factors of the tumors, en-TNF was produced in 21 of a total of 44 patients. The group of patients with clear en-TNF production showed a significantly lower incidence of recurrence and/or metastasis and a higher survival rate than the group without en-TNF production, suggesting a strong correlation between patient prognosis and inducibility of en-TNF. CONCLUSION: Inducibility of en-TNF by tumor cells themselves can be a novel prognostic factor for patients with colorectal tumor, especially of Dukes Stage C.

Biomarkers↗

PubMed1995

Role of the kidney in the plasma clearance of angiotensinogen in the rat: plasma clearance and tissue distribution of 125I-angiotensinogen.

We studied the tissue distribution and plasma clearance of angiotensinogen (AGN) in rats following an i.v. injection of 125I-labeled AGN. The plasma clearance rate of [125I]AGN fits a two-compartment model with half-lives of 10.2 +/- 1.5 min and 4.1 +/- 0.5 h in non-treated rats, and the half-life of slower phase significantly increased to 10.2 +/- 1.1 h following bilateral nephrectomy. Radioactivity was predominantly distributed in the kidneys (4.9%), and to a lesser extent in the liver (1.8%), testis (1.2%), spleen (0.61%), heart (0.35%), lung (0.18%), thymus (0.03%) and brain (0.03%). The subcellular distribution of radioactivity in the kidney was 64% in the soluble fraction and 33% in the crude mitochondrial-lysosomal fraction. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed that the radioactivity in the soluble fraction consisted of proteins corresponding to intact [125I]AGN, whereas the mitochondrial-lysosomal fraction contained additional radioactive proteins with molecular weights between 18,000 and 29,000. When isolated kidney cells were incubated with [125I]AGN at 0 degree C, the radioactive binding was saturable and specific with a Kd value of 4.8 x 10(-11)M, whereas incubation at 37 degrees C resulted in the appearance of degraded products of [125I]AGN in the medium. These results suggested that circulating AGN is cleared mainly by the kidneys via receptor-mediated endocytosis, which may play an important role in regulating plasma level of AGN.

Angiotensinogen↗

PubMed1995

Angiotensinogen synthesis in the liver is independent of physiological estrogen levels.

We determined the physiological importance of endogenous estrogen in the regulation of angiotensinogen synthesis in the liver. The plasma levels of angiotensinogen and hepatic levels of angiotensinogen mRNA were studied in the rat in comparison to those of T-kininogen, a plasma protein whose synthesis in the liver is primarily estrogen-dependent. Plasma levels of T-kininogen and hepatic levels of T-kininogen mRNA were 3- and 2-fold higher in adult females, respectively, than in adult males, whereas there were no sex differences in levels of either plasma angiotensinogen or hepatic angiotensinogen mRNA. Ovariectomy in female rats abolished the sex differences in the levels of plasma T-kininogen and hepatic T-kininogen mRNA, but it did not affect those of plasma angiotensinogen and hepatic angiotensinogen mRNA. These results suggest that, in contrast to T-kininogen, angiotensinogen synthesis in the liver is unlikely to be controlled by endogenous levels of estrogen.

Aging↗

PubMed1995

Identification of organic cation transporter in rat renal brush-border membrane by photoaffinity labeling.

As an approach to identification of the organic cation transport system in brush-border membranes, we designed a photoaffinity probe, 1-cyano-2-(4-azido[3,5-3H]benzoylethyl)-3-[2-[[(5-methyl-4-imidazo lyl ) methyl]thio]ethyl]-guanidine ([3H]AMC) based on the molecular structure of cimetidine, which is taken up by the organic cation transport system in brush-border membrane vesicles. The effect of nonradioactive 1-cyano-2-(4-azidobenzoylethyl)-3-[2-[[(5-methyl-4- imidazolyl)methyl]thio]ethyl]guanidine (AMC) on tetraethylammonium uptake was investigated in rat renal brush-border membrane vesicles. We examined the photolysis of AMC in which the azido group was converted to an active nitrene group using UV light at a wavelength of 254 nm and established a half-life of 7 s. This half-life duration did not significantly impair brush-border membrane vesicles during the exposure to light for photo-labeling. Photoaffinity labeling of brush-border membrane vesicles from the rat renal cortex with [3H]AMC resulted in the covalent incorporation of radioactivity into membrane polypeptides; an apparent 36 kDa polypeptide was predominantly labeled. Photolabeling specificity was shown by a reduction in the labeling of the 36 kDa polypeptide in the presence of organic cations, cimetidine, tetraethylammonium and N-methylnicotinamide whereas the organic anion, fur osemide, had no effect on labeling patterns. These data demonstrate that AMC, as well as organic cations, cimetidine, tetraethylammonium and N-methylnicotinamide, interact with a common 36 kDa membrane polypeptide, which may be the transport system or one of its brush-border membrane components.

Affinity Labels↗

PubMed1995

Activation of the renin-angiotensin system in anti-glomerular basement membrane antibody-induced glomerulonephritis.

Activity of the renin-angiotensin system in the nephrotic syndrome was investigated in rats with acute nephritis induced by anti-glomerular basement membrane (GBM) antibody. Injection of anti-GBM antibody resulted in a transient 2-fold elevation of both plasma renin and angiotensinogen with a peak at 12 h. Angiotensinogen mRNA levels in the liver also rapidly and transiently increased 4-fold at 3 h. The manifestation of acute nephritis, indicated by proteinuria, hypoalbuminemia, hypercholesterolemia and an increase in serum creatinine, following injection of anti-GBM antibody, was inhibited by a single administration of the selective angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg, p.o.) 2 h before an injection with the antibody, but not by successive administration of this drug for 1 week from 3 d after the injection of antibody. These results suggested that the enhanced generation of angiotensin II by elevated levels of both renin and its substrate in the early phase of anti-GBM nephritis promotes the evolution of acute nephritis via angiotensin II type 1 receptor.

Angiotensin Receptor Antagonists↗

PubMed1995

Role of angiotensin II in the transforming growth factor-beta 1 expression of rat kidney in anti-glomerular basement membrane antiserum-induced glomerulonephritis.

Induction of acute nephritis in the rat by injecting anti-glomerular basement membrane (GBM) antiserum is accompanied by a transient increase in angiotensin II generation in blood circulation within the first 24 h and a subsequent elevation of transforming growth factor-beta 1 (TGF-beta 1) mRNA levels in kidney cortex with a peak at days 7-8. Studies were carried out to determine whether the increased generation of angiotensin II plays a role in the elevation of TGF-beta 1 mRNA. Elevation of TGF-beta 1 mRNA levels 7 d after injection of antiserum was significantly inhibited by a successive daily administration of TCV-116, angiotensin II type 1 receptor antagonist, at 1 mg/kg/d from days 0 to 2 or from days 0 to 6, while it was not influenced by a single administration of this dose on day 0. In addition, angiotensin II infusion or 24 h at a rate of 50 ng/min did not alter the level of TGF-beta1 mRNA which was measured 6 d after the infusion. These results suggest that the anti-GBM antiserum-induced increase in TGF-beta 1 expression in the kidney is not responsible for angiotensin II generated in the blood circulation during the early phase of acute nephritis, but iis probably mediated by angiotensin II generated locally in the kidney.

Angiotensin II↗

PubMed1995

[Efficacy of beraprost sodium on Raynaud's phenomenon in patients with systemic sclerosis].

Raynaud's phenomenon is an important clinical manifestation in patients with systemic sclerosis (SSc). No effective therapy, however, has been established for this phenomenon. Beraprost sodium, a stable prostacycline (PGI2) analogue, has been reported to improve hemorrheological impairment in patients with rheumatic diseases. In this study, we, therefore, examined the efficacy of beraprost sodium on Raynaud's phenomenon in 30 patients with SSc. Sixty micrograms per day of beraprost sodium was found to be effective in 14 patients (47%) in the period of 15.0 +/- 12.5 weeks. Raynaud's phenomenon in patients who responded to beraprost sodium was characterized by infrequent nail fold thrombosis and narrower hand areas affected by Raynaud's phenomenon, with mild secondary symptoms such as pain. These results indicate that beraprost sodium is effective for mild forms of Raynaud's phenomenon in patients with SSc.

Adult↗

PubMed1995

[Spinal multiple sclerosis mimicking a spinal cord tumor: a case report].

Since the advent of magnetic resonance imaging (MRI), to visualize lesions of multiple sclerosis has become easy to do. However, in some cases with primary spinal cord multiple sclerosis, it is not always easy to obtain a diagnosis in the first instance. We reported a case of primary spinal multiple sclerosis diagnosed through histological examination of a surgical specimen taken by an open biopsy. A 35-year-old woman was admitted with complaints of two-months duration of progressive weakness and sensory disturbance in the legs and buttocks. On radiological examinations including metrizamide CT myelography and MRI, enlargement of the conus medullaris was the only positive finding. Respective to her clinical course, intramedullary spinal cord tumor could not be ruled out, so an open biopsy was performed. Histological examination revealed that the cord lesion was acute demyelination with perivascular inflammation. Her neurological signs were almost completely cured with administration of corticosteroid, though new brainstem signs took place two months later and then a concrete diagnosis of her having multiple sclerosis was finally achieved. Since preoperative examinations can not differentiate spinal cord tumor from any other intramedullary cord lesions such as demyelinating foci of multiple sclerosis, surgical intervention would be approved in such atypical primary spinal cord multiple sclerosis.

Adult↗

PubMed1995

Specificity of p-aminohippurate transport system in the OK kidney epithelial cell line.

Substrate specificity of the p-aminohippurate (PAH) transport system was investigated in the OK kidney epithelial cells. PAH uptake by OK cells from the basal side was inhibited by beta-lactam antibiotics such as benzylpenicillin (PCG) and cefazolin. The inhibition of PAH uptake by PCG was competitive and the Ki value was calculated as 108.8 microM. Transcellular transport of PCG across OK cell monolayers occurred unidirectionally from the basal to apical side, and transcellular transport and basolateral uptake were inhibited by PAH, probenecid and beta-lactam antibiotics. The basolateral uptake of cefazolin and cefotiam was also inhibited by PAH and probenecid. The basolateral uptake of PAH and PCG were not affected by aliphatic dicarboxylates with 3 or 4 carbon atoms, but were strongly inhibited by those with 5 or 6 carbon atoms. The inhibitory effect became weaker for a longer dicarboxylate with 7 carbon atoms, then increased again with increasing number of carbon atoms. Such a pattern of inhibition by dicarboxylates is essentially the same with that observed in rat renal proximal tubules in situ. These findings suggest that the PAH transport system in OK cells has a substrate specificity similar to that in rat renal proximal tubules, which is involved in the active secretion of various organic anions including drugs.

Animals↗

PubMed1995

Patent vitelline duct in an adult deceptively appeared to be acquired umbilical urachal sinus: a case report.

Here is presented a surprisingly rare case in a 40-year-old male who had patent vitelline duct by nature. However, his congenital disease appeared deceptively to be an acquired umbilical urachal sinus on the diagnostic evaluations including fistulography before surgery. The diagnosis was definitely confirmed after the successful surgical procedure. The principal reason why these diseases were indistinguishable was reviewed. The incidence of each disease and incidence of association with umbilical fistula in each disease were discussed. With regard to these incidences, we compared urachal anomalies with vitelline duct anomalies through reference of several literatures. This is the most unique event we have ever clinically experienced.

Adult↗

PubMed1995

Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells.

Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.

Animals↗

PubMed1994

High-performance liquid chromatographic determination of catecholamine metabolites and 5-hydroxyindoleacetic acid in human urine using a mixed-mode column and an eight-channel electrode electrochemical detector.

An HPLC system for the simultaneous determination of acidic catecholamine metabolites, related compounds and 5-hydroxyindoleacetic acid (5-HIAA) in human urine was developed. A mixed-mode (C18/anion-exchange) column with isocratic elution using citrate buffer and an eight-channel electrochemical detector were used. Vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenyllactic acid (vanillactic acid, VLA), homovanillic acid (HVA), vanillic acid (VA) and 5-HIAA in urine were determined simultaneously. Detection limits and inter (n = 5) and intra-assay (n = 5) coefficients of variation were satisfactory. The mean of analytical recoveries (n = 3, +/- C.V. (%)) were between 97 +/- 3.2 (VMA) and 105 +/- 4.8 (VA). Correlations between the analytical results for VMA, HVA and 5-HIAA obtained by an established method and the present method were satisfactory. The mean +/- 2 S.D. of the excretion rates of VMA, DOPAC, VLA, HVA, 5-HIAA and VA in urine from healthy adult volunteers were 0.61-4.36, 0.13-1.02, 0-0.35, 0.67-6.55, 0.50-5.14 and 0-0.55 mg/g creatinine, respectively.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Critical period for degradation of adult rat retinal ganglion cells and their regeneration capability after axotomy.

The optic nerve (ON) in adult rats was transected intraorbitally followed by retrograde labelling of retinal ganglion cells (RGCs) with fluorescence dye (DiI). A two phase reduction of axotomized RGCs was represented in the retina until 15 days after ON transection. The critical period of RGC loss is around 7 days after axotomy. In this period, the capability of neurite regeneration from RGCs in culture was strongly intensified by ON transection. These findings indicate that the 7th day after axotomy is important for both RGC survival and regeneration.

Animals↗