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Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 199 records · Page 11Linked to original sources
PubMed1996

[Changes of regional perfusion in metastatic brain tumor and peritumoral area after radiosurgery: a study by 123I-IMP dynamic SPECT].

Changes of regional perfusion in the tumor, peritumoral edematous area and juxtatumor brain after radiosurgical treatment for metastatic brain tumor were investigated by dynamic SPECT using 123I-IMP. The SPECT was performed in 12 patients before and 1, 7 and 30 days after stereotactic irradiation. A region of interest (ROI) was selected each in the tumor, peritumoral edematous area, juxtatumor brain and ipsilateral cerebellum. Radioactivity in each ROIs was counted on early SPECT based on dynamic SPECT from 0 to 5 minutes. Mean count/pixel in each ROIs was divited by mean count/pixel in the ROI of the ipsilateral cerebellum and its value was designated as a count ratio (CR). Assuming the pre-treatment CRs are 1.0, relative changes of post-treatment CRs investigated. rCR in the tumor did not show any significant change after radiosurgical treatment. rCR in the edematous area and the juxtatumor brain increased at 7 days after irradiation [Mean +/- SD 1.43 +/- 0.409 (p < 0.05), 1.248 +/- 0.228 (p < 0.05) by Mann-Whitney test] and at 30 days [1.359 +/- 0.245 (p < 0.01), 1.301 +/- 0.287 (p < 0.01)] respectively. Computed tomography revealed no change in the maximum diameter of the tumor at 1 month after irradiation but a significant reduction in the diameter [0.744 +/- 0.227 (p < 0.02)] at 2 months. Early improvement of regional cerebral blood flow in the juxtatumor areas after radiosurgery suggested that radiosurgery could be effective treatment for metastatic brain tumor.

Adenocarcinoma↗
PubMed1996

[High uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) demonstrated by dynamic SPECT in some cases of glioma].

Selective high uptake of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) in the brain tumors is not common, the mechanism of uptake in the brain tumor is not yet clearly understood. Among 26 cases of gliomas investigated by dynamic SPECT, 4 cases including 2 cases of anaplastic astrocytoma and 2 cases of oligodendroglioma, showed high uptake of 123I-IMP. New three detector type camera which enables us to investigate rapid successive scanning, was used in our study. In dynamic SPECT, 15 successive scans of 2 minutes interval were made for 30 minutes after administration of 123I-IMP. In addition, quick dynamic SPECT was tried in 2 cases, in which 10 quick successive scans of 24 seconds interval were investigated for initial 4 minutes immediately after administration of 123I-IMP. Radioactivity in the region of interest inside the tumor (T) and radioactivity of the corresponding site in the contralateral hemisphere (C) was measured respectively, and T/C ratio was calculated. Time course change of radioactivity (time activity curve: TAC) was analyzed in all cases. Radioactivity was always higher in the tumor and the average T/C ratio was 1.40. TAC showed rapid increase of 123I-IMP in the tumor during initial 2 minutes after administration and keeping its high plateau level for 30 minutes. Angiography in these cases revealed a remarkable tumor stain. On the other hand, these gliomas showed no or slight enhancement effect in CT or MRI. These findings are interpretable as that early high uptake of 123I-IMP in some gliomas is attributable to an increased vascular bed and blood flow with no or minimal derangement of blood brain barrier in these tumors.

Adult↗
PubMed1996

[An application of semiquantitative analysis of pulmonary scintigram to pulmonary tuberculosis sequelae].

We performed ventilation-perfusion scintigraphy in 13 patients with pulmonary tuberculosis sequelae and 21 with chronic obstructive pulmonary disease. We used 99mTc-MAA for perfusion scintigram and 133Xe gas for ventilation scintigram. We added the radioactivities during the rebreathing phase of the ventilation scintigram to make a computerized image of the lung volume. Regions of interest (ROIs) were derived from radioactivities on each image. ROIs included each whole lung on lung volume (L) image and areas where radioactivity was greater than 70% of the highest radioactivity on perfusion (P70) image. We counted the area of ROIs on L and P70, and used the ratio of perfusion to lung volume (P70/L) as a parameter of pulmonary perfusion. P70/L in patients with pulmonary tuberculosis sequelae was significantly higher than that in those with COPD. This suggested that the area of high pulmonary perfusion is larger in the patients with pulmonary tuberculosis sequelae as compared with those with COPD.

Aged↗
PubMed1996

[Axonal regeneration of retinal ganglion cells].

We have developed retinal culture system of adult mammals to investigate neural regeneration from adult retinal ganglion cells (RGC). In this culture system, neurites were regenerated from RGCs of adult retinal explants. Investigation of neurotrophic effects on the neural regeneration showed that some interleukins and neurotrophins enhanced neurite regeneration from adult rat RGCs. We also found that the adult human retina had the ability of neural regeneration and that neurotrophins enhanced this ability. A novel neurotrophic factor secreted by adult rat hepatocytes also enhanced neurite regeneration not only in adult mice but also in aged RGCs. This result indicated the novel hepatocyte secreted factor is an activator which enhances neural regeneration of the aged retina. We concluded that even adult aged RGCs had the ability of axonal regeneration after injury and that neurotrophic factors might enhanced these abilities. Therefore neurotrophic factors might have practicable applications in drug treatments for intractable disease of the neural retina and optic nerve. Future progress of neuroscience is expected to rescue the retina from various diseases, and to render possible the transplantation of the retina and optic nerve.

Adult↗
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

Non-selective cation current of guinea-pig endocardial endothelial cells.

1. Endocardial endothelial (EE) cells, isolated by the enzymatic treatment of guinea-pig heart, were used for whole-cell voltage clamp experiments. 2. The inward rectifier K+ current was observed in about half of the experiments. The contribution of Ca(2+)-dependent K+ current to the resting membrane conductance was also suggested. 3. After the K+ conductances were suppressed, removal of external Na+ revealed an inward cation current (1.2 pA pF-1, at -45 mV), whose slope conductance was a saturable function of external Na+ concentration. When Na+ was totally replaced by various monovalent cations, the order of the membrane conductances was K+ > Rb+ > Cs+ > Na+ > Li+. 4. This basal non-selective cation current was blocked by either Gd3+ or La3+, and showed slight outward rectification. 5. Addition of 20 mM Ca2+ or Ba2+, but not Mg2+ or Mn2+, to the Na(+)-free solution, induced an inward current, indicating that this current possesses a significant Ca2+ permeability. 6. In approximately 15% of the experiments, ATP and histamine induced another type of non-selective cation current, which showed different ion selectivity (Na+ > K+, Cs+) and rectification (inward). 7. The basal non-selective cation current is responsible for both the low resting potential and the leak Ca2+ influx of EE cells.

Adenosine Triphosphate↗
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↗