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Biomedical subjects

T Suga

Publications and source records attributed to T Suga.

At least 109 records · Page 6Linked to original sources

Transcatheter arterial embolization for massive bleeding from duodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND STUDY AIMS: We evaluated the efficacy of transcatheter arterial embolization (TAE) in patients in whom endoscopic hemostasis of a massively bleeding duodenal ulcer failed. PATIENTS AND METHODS: TAE was performed in 11 patients with endoscopically uncontrollable massively bleeding duodenal ulcers, and the results and long-time outcome were studied. Two additional cases of failed endoscopic hemostasis were treated surgically without TAE. The entire group of 13 patients represented 5% of endoscopically treated duodenal ulcers and 0.6% of all cases with upper gastrointestinal bleeding who underwent emergency endoscopy (n = 2073). All but one of these 13 patients had concomitant disease. RESULTS: Arteriograms performed before TAE revealed extravasation of contrast material around the gastroduodenal artery (GDA), the anterior superior pancreaticoduodenal artery (ASPD), or the posterior superior pancreaticoduodenal artery (PSPD) in six of 11 cases. We failed to stop the bleeding in one patient, in whom only the common hepatic artery side of the GDA bleeding site was embolized; this patient died. TAE was successful in the other ten patients, in whom the long stretch of the GDA, including the ASPD and PSPD, was embolized around the bleeding site. Two surgically treated patients died within a week. CONCLUSIONS: Our findings indicate that TAE may induce hemostasis in 90% of patients with serious concomitant diseases who have endoscopically uncontrollable massive bleeding from duodenal ulcers.

Aged↗

Pharmacological activity of the C-terminal and N-terminal domains of secretory leukoprotease inhibitor in vitro.

1. In order to characterize the physiological functions of the domain structure of secretory leukoprotease inhibitor (SLPI), the biological capacities of half-length SLPIs, (Ser1-Pro54)SLPI and (Asn55-Ala107)SLPI, were investigated and compared with those of full-length SLPI. 2. The activities of these inhibitors against several serine proteases were determined using synthetic chromogenic substrates. The inhibitory capacity of the C-terminal domain, (Asn55-Ala107)SLPI, was as strong as that of full-length SLPI against human neutrophil elastase (NE), cathepsin G and chymotrypsin. It possessed less trypsin inhibitory activity than intact SLPI. For the N-terminal domain of SLPI, (Ser1-Pro54)SLPI, no inhibitory activity could be detected against the serine proteases tested in this study. 3. The inhibitory activity of (Asn55-Ala107)SLPI against the proteolysis of the natural substrates elastin and collagen by NE was comparable with that of full-SLPI (elastin, IC50 = 907 +/- 31 nM for SLPI, 767 +/- 33 nM for (Asn55-Ala107)SLPI; collagen, IC50 = 862 +/- 36 nM for SLPI, 727 +/- 47 nM for (Asn55-Ala107)SLPI). 4. The binding affinities of full- and half-length SLPIs for heparin were measured by affinity column chromatography. Full-length SLPI showed high affinity for heparin while the binding capacities of both half-length SLPIs were lower. (Concentration of NaCl for elution, 0.45 M for SLPI, 0.24 M for (Ser1-Pro54)SLPI, 0.27 M for (Asn55-Ala107)SLPI). 5. The effects of full-SLPI and (Asn55-Ala107)SLPI on blood coagulation were measured using the activated partial thromboplastin time (APTT). Full-length SLPI prolonged clotting time dose dependently(1.25, 2.5 and 5.0 microM), whereas (Asn55-AlalO7)SLPI had no effect even at the highest concentration.6. In conclusion, the C-terminal domain of SLPI is a promising candidate for the treatment of inflammatory diseases in which participation of neutrophil proteases has been suggested.

Animals↗

Serum levels of soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alpha.

BACKGROUND: Serum levels of soluble interleukin-2 receptor (sIL-2R) seem to serve as a marker for the activation of T lymphocytes. The aim of this study was to evaluate the clinical significance of such levels in patients with chronic hepatitis C (CHC) treated with interferon. METHODS: We measured serum levels of sIL-2R in 37 patients with CHC before and after treatment with recombinant interferon-alpha. Serum receptor levels were then compared with the response of the hepatitis C virus (HCV)-RNA level in serum after interferon. RESULTS: Receptor levels were significantly higher in the patients with chronic persistent hepatitis and chronic active hepatitis than in normal controls (p < 0.01). There was a weak correlation between serum sIL-2R and alanine aminotransferase (ALAT) levels (r = 0.14, p = 0.010). Patients were then classified into three groups on the basis of the effect of interferon treatment on HCV-RNA levels in serum: sustained response (SR; n = 21), non-sustained response (NSR; n = 14), and nonresponse (NR; n = 2). Before and during interferon treatment the serum sIL-2R level remained increased in the SR group and in the combined groups with NSR or NR. However, after interferon was withdrawn, the serum sIL-2R decreased in the SR group but remained significantly increased in the combined response group (p < 0.01-0.05). CONCLUSION: This finding seems to reflect the disappearance of HCV-RNA from the serum of the patients with an SR, and monitoring of sIL-2R levels may therefore be of value as an adjunct to the measurement of serum ALAT and HCV-RNA in evaluating the response to the interferon therapy for CHC.

Adult↗

[A surgically treated case of ventrally exophytic pontine glioma].

A surgically treated case of ventrally exophytic pontine glioma is reported. A 49-year-old woman, complaining of dysarthria, dysphagia and gait disturbance, was admitted to our department. Her past history included bronchial asthma. Plain skull x-p and tomography revealed destruction of the dorsum sellae and upper clivus. CT demonstrated an enhanced oval mass at the ventral side of the upper brainstem. The mass was severely compressing the brainstem dorsally. MRI revealed a low-intensity band between the tumor and the brainstem. Dynamic MRI demonstrated a pattern of rapid increasing and slow reduction. Cerebral angiogram demonstrated a paradoxical sign that pontine branches were located anterior to the basilar artery. The finding demonstrated that the tumor was an intraaxial mass. The first operation was performed by the orbitofrontomalar approach. On the trans-sylvian route, the tumor was removed partially with CUSA and neuronavigation system. Its histology was astrocytoma grade III. Radiation therapy was added. The patient's symptoms aggravated again. On the second operation, the transtemporal route with tentorial resection was chosen. Under a wide visual field, intracapsular subtotal resection of the tumor was performed. Interferon therapy was added. She was discharged to her home with no neurological deficits. Ventrally exophytic pontine glioma is very rare. Low-intensity band of MRI, a sign of extraaxial mass, was visualised in our case. On the other hand, cerebral angiogram demonstrated a paradoxical sign. This sign suggested that the tumor originated from the brainstem. With update skull base surgery and neuronavigation system, surgical therapy of ventrally exophytic pontine glioma is safe and effective.

Brain Neoplasms↗

[A case of hemorrhagic mixed cerebrovascular malformation of the brainstem draining through a transpontine vein].

A case of mixed cerebrovascular malformation of the brainstem with pontine hemorrhage is reported. The mixed cerebrovascular malformation was composed of medullary venous malformation, one hemorrhagic and another non-hemorrhagic mass. The latter masses were thought to be cavernous venous malformations by their MR findings. The medullary venous malformation drained to the anterior pontomesencephalic vein through a transpontine vein. A 70-year-old man, complaining of aggravation of left hemiparesis, was admitted to our department. His past history included traumatic cervical myelopathy and diabetic neuropathy. CT revealed a pontine hemorrhage with linear enhancement. Depending on MRI findings, the hemorrhage was thought to be an intratumoral hemorrhage within the cavernous venous malformation. Cerebral angiogram demonstrated medullary venous malformation. The malformation drained to the anterior pontomesencephalic vein through a transpontine vein. The linear enhancement was the transpontine vein itself. Medullary venous malformations in the brainstem are rare. With MRI, the transpontine vein is thought to be a characteristic feature of medullary venous malformation of the brainstem. We suggest that most cases of hemorrhagic medullary venous malformations are mixed cerebrovascular malformations. We emphasize the need for precise examination of other types of vascular lesions coexisting with medullary venous malformations.

Aged↗

[A case of complex brain anomaly with arachnoid cyst treated well by cyst-cisternal shunt].

A rare case of complex anomaly, composed of schizencephaly, polymicrogyria, heterotopic gray matter, agenesis of the septum pellicidi and arachnoid cyst at the right middle cranial fossa was encountered. A 38-year old man, complaining of epileptic seizure, was admitted to our department. His past history included cerebral palsy. Plain skull roentgenogram showed protrusion of the right temporal bone and thinning of the ipsilateral sphenoidal wing. CT revealed arachnoid cyst and parietal crest surrounded by cortical layer on the right side. MRI also demonstrated the arachnoid cyst, parietal crest and agenesis of septum pellicidi. MRI, especially proton density weighted image, well demonstrated cortical layer surrounding the parietal crest, right opercular polymicrogyria and left heterotopic gray matter. The crest was diagnosed as schizencephaly. The arachnoid cyst was treated by cyst-cisternal shunt with a silicone tube (Sapporo shunt) after fenestrating the cyst. The tube was inserted into the sylvian fissure from the cyst and sutured to the inner wall of the cyst. Despite slight intratumoral hemorrhage in the CT at 1.5 months after the operation, the cyst markedly decreased in size. As to the diagnosis of the brain anomaly, MRI gives extremely useful information. Particularly for the diagnosis of anomalies of migration of neuronal cells, MRI, especially proton density weighted image, has been regarded as an indispensable examination. In the operation of subarachnoid cyst, to maintain the flow between the inside of its cyst and the basal cistern, cyst-cisternal shunt with a silicone tube had satisfactory results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Suppressive effect of growth hormone on the expression of peroxisome proliferator-activated receptor in cultured rat hepatocytes.

The effect of growth (GH) and thyroid hormones (triiodothyronine, T3) on the expression of peroxisome proliferator-activated receptor (PPAR alpha) was examined using Northern blotting in primary cultures of rat hepatocytes. Exposure of the hepatocytes to GH at the concentrations of 5-500 ng/ml for 1 day decreased the steady state level of PPAR mRNA by 20-30% compared with the control. The decrease in the mRNA level reached about 50% after a 5-day exposure to 50 or 500 ng/ml GH. However, the PPAR mRNA level was increased by 30-50% in hepatocytes exposed to T3 at 30 or 300 nM. These findings suggest the suppression of PPAR expression as a possible mechanism for the GH-mediated suppression of the induction of peroxisomal beta-oxidation caused by peroxisome proliferators (PPs), whereas T3 may act in the other way to exert its suppressive effect on the PP induction of peroxisomal enzymes.

Animals↗

Specific binding of dehydroepiandrosterone sulfate to rat liver cytosol: a possible association with peroxisomal enzyme induction.

Incubation of [3H]dehydroepiandrosterone sulfate (DHEAS) with rat liver cytosol demonstrated its specific binding with a dissociation constant of 72 +/- 14 nM and a maximal binding capacity of 312 +/- 105 fmol/mg cytosol protein. The binding correlated with the amount of cytosol protein, and depended on time, temperature and pH, with equilibrium being reached after 6 h at 0 degrees C and pH 7.5. Boiling or treatment of the cytosol with proteases or sulfhydryl-blocking reagents affected the binding. The apparent molecular mass of the binding entity was estimated to be 160-230 kDa by HPLC gel filtration. In competitive binding studies, free steroids, including dehydroepiandrosterone (DHEA), sulfatase substrates and ligands of organic anion binders such as ligandin and fatty acid binding protein, had no effect on the [3H]DHEAS binding. Peroxisome proliferators also had no effect, except Wy-14,643. Competition with various steroids related to DHEAS revealed strict structural requirements for DHEAS binding, in which epiandrosterone sulfate was almost as effective as unlabeled DHEAS in inhibiting [3H]DHEAS binding. These findings indicated the presence of a binding protein highly specific to DHEAS in rat liver cytosol. The DHEAS binding in liver cytosol was 2-fold higher in male than in female rats. The cytosolic DHEAS binding was highest in the liver, followed by the kidney and heart. The possibility of association between the DHEAS binding and DHEA induction of peroxisomal beta-oxidation is discussed.

Animals↗

Specific cleavage of secretory leukoprotease inhibitor by neutrophil elastase and saliva.

In an attempt to explore the process of naturally occurring secretory leukoprotease inhibitor (SLPI) fragmentation, the cleavage profile of SLPI, which had been prepared by recombinant techniques, was investigated biochemically. Restricted fragments of SLPI were detected using SDS-PAGE after treatment with human neutrophil elastase (NE) or normal saliva and sequenced at their cleavage sites. Among these restricted fragments, two species of nearly half-length SLPIs that contained the C-terminal domain, (Arg58-Ala107)SLPI and (Arg59-Ala107)SLPI, were detected. They were both as active at inhibiting NE as the parent SLPI. These results suggest that functional SLPI derivatives may be generated physiologically in the respiratory tract under inflammatory and healthy conditions.

Amino Acid Sequence↗

Effects of testosterone, hypophysectomy and growth hormone treatment on clofibrate induction of peroxisomal beta-oxidation in female rat liver.

Induction of peroxisomal beta-oxidation by clofibrate under altered hormonal states was investigated in female rat liver. Treatment of rats with clofibric acid (CPIB) caused a significant increase in hepatic peroxisomal beta-oxidation, with female rats being less responsive than males (4.2- vs 12.2-fold increase). However, testosterone treatment following ovariectomy of female rats resulted in an enhanced response to CPIB, giving an induction (11.7-fold) comparable to that seen in male rats. Hypophysectomy of female rats also enhanced the induction (8.2-fold compared with 5.1-fold), suggesting a suppressive effect of a pituitary-dependent factor on CPIB induction of peroxisomal beta-oxidation. Continuous infusion of growth hormone to the hypophysectomized female rats suppressed the enhanced induction nearly to the initial level (6.1-fold). The stimulatory effects of testosterone and hypophysectomy on the enzyme induction were additive. These findings suggest the involvement of growth hormone, as well as male sex hormone, in regulating the responsiveness to CPIB induction of peroxisomal beta-oxidation in rat liver.

Animals↗

Contractile actions of endothelins in rat gastric body: evidence for receptor subtypes and involvement of prostaglandin E2.

Endothelin-1 produced a phasic contraction in the longitudinal muscle preparation isolated from the rat gastric body, but produced a sustained contraction in the circular muscle preparation. Indomethacin, a cyclo-oxygenase inhibitor, decreased the endothelin-1-induced contraction of the longitudinal preparation, but did not affect the endothelin-1-induced contractions of the circular muscle. In the absence of indomethacin, the maximal contractile tension (Emax) and the concentration producing a half-maximal contraction (EC50) induced by endothelin-3 in the longitudinal muscle preparations were smaller than those for endothelin-1, whereas in the circular muscle preparations there were no significant differences between the values (EC50, Emax) for endothelin-1 and endothelin-3. In the presence of indomethacin, endothelin-3-induced contraction of the longitudinal muscle preparation is more potent than that of endothelin-1. SC-19220, a prostaglandin E2 receptor antagonist, significantly decreased endothelin-1-induced contraction of the longitudinal preparation, prostaglandin E2 produced a concentration-dependent contraction in the longitudinal preparation, but had no effects in the circular muscle preparation. Endothelin-1 (10(-8) M) significantly increased the release of immunoassayable prostaglandin E2 from rat gastric smooth muscle. These results point to the existence of distinct endothelin receptor subtypes in the smooth muscle of rat gastric body, and a potential role of endothelin-1 in regulating gastric motility. Moreover, one of the endothelin receptor subtypes is related to the production of prostaglandin E2.

Animals↗

Purification and properties of long-chain acyl-CoA hydrolases from the liver cytosol of rats treated with peroxisome proliferator.

Two long-chain acyl-CoA hydrolases, referred to as ACH1 and ACH2, were purified from the liver cytosol of rats fed a diet containing di(2-ethylhexyl)phthalate, a peroxisome proliferator. The molecular mass of ACH1 was estimated to be 73 kDa by gel filtration, and that of the subunits, 36 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The corresponding values of ACH2 were 42 and 43 kDa, respectively. Both enzymes were active toward fatty acyl-CoAs with chain-lengths of C12-16, but ACH1 had relatively broad specificity as acyl-CoAs with C8-18 were good substrates. A marked difference in their catalytic properties was found in the maximal velocity; for palmitoyl-CoA, 553 and 4.23 mumol/min/mg with Km values of 5.9 and 5.4 microM for ACH1 and ACH2, respectively. ACH2 underwent severe substrate inhibition with high concentrations of long-chain acyl-CoAs, whereas ACH1 did not. Examination with various reagents including divalent cations, sulfhydryl-blocking reagent, nucleotides, and hypolipidemic drugs, characterized ACH1 and ACH2 with several properties distinct from those of mitochondrial and microsomal hydrolases. ACH1 and ACH2 were also discernible in that the former, but not the latter, was inhibited by ATP. In the liver cytosol of rats treated with di(2-ethylhexyl)phthalate, about 90% of palmitoyl-CoA hydrolase activity was titrated with anti-ACH1 and anti-ACH2 antibodies. Immunoblot analysis suggested the presence of the enzymes also in extrahepatic tissues, especially in the brain and testis (ACH1), and in the heart and kidney (ACH2).

Animals↗

Gou-teng (from Uncaria rhynchophylla Miquel)-induced endothelium-dependent and -independent relaxations in the isolated rat aorta.

Gou-teng is a drug used for treatment of hypertension in Chinese medicine. Its antihypertensive action has been previously confirmed in the spontaneously hypertensive rat (SHR). Here, its vasorelaxing effect and the mechanisms of actions were studied in vitro. Gou-teng extract (GTE) relaxed the norepinephrine (NE)-precontracted aortic ring preparations isolated from Wistar Kyoto rats (WKY) with and without intact endothelium; the latter was significantly less sensitive than the former. The GTE-induced endothelium-dependent relaxation was significantly inhibited by NG-monomethyl-L-arginine (NMMA) in a dose-dependent manner while indomethacin did not affect the relaxation. Atropine inhibited the acetylcholine (ACh)-induced endothelium-dependent relaxation but did not the GTE-induced one. Furthermore, once GTE was applied, the following NE-induced contraction was significantly reduced even after repeated washout. NMMA effectively reduced and rather reversed this residual effect of GTE. From these results, it is concluded that GTE relaxes the NE-precontracted rat aorta through endothelium-dependent and, to lesser extent, -independent mechanisms. The endothelium-dependent component would be mediated by EDRF/NO pathway in which the muscarinic cholinoceptors were not involved. Thus, GTE appears to be a potent and long-lasting vasodilator mainly through EDRF/NO release.

Acetylcholine↗

Biotransformation of alpha- and beta-ionones by immobilized cells of Nicotiana tabacum.

Immobilized cells of Nicotiana tabacum reduced the carbon-carbon double bond adjacent to the carbonyl group and then the carbonyl group itself of the dienone compounds, alpha-ionone and beta-ionone. In addition, the selectivity for the reduction of the double bond adjacent to the carbonyl group could be enhanced by performing the biotransformation in medium with a pH near the optimal pH of the enone reductase which specifically catalyses the reduction of the alpha, beta-unsaturated double bond of s-trans-enones.

Biotransformation↗

Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats.

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.

8-Hydroxy-2'-Deoxyguanosine↗

Synergistic antimetastatic effects of lentinan and interleukin 2 with pre- and post-operative treatments.

The antimetastatic activity of a combination of lentinan and interleukin 2 (IL-2) was evaluated against spontaneously metastatic 3-methylcholanthrene-induced DBA/2.MC.CS.T fibrosarcoma. Although pre-operative treatment with either IL-2 or lentinan alone exerted little effect on the reduction of lung metastasis colony numbers (7.1% or 28.4% reduction, respectively), the combination exhibited a synergistic effect (85% reduction). Furthermore, 3 of 13 mice given the pre-operative combination treatment achieved complete cure, while no mice given saline did. Although the post-operative combination treatment also reduced the colony number (71% reduction), it caused little prolongation of survival and no mouse achieved complete cure. Synergistic effects were observed between pre- and post-operative treatments with lentinan and IL-2: 8 of 12 mice were completely cured. The anti-metastatic activity was abolished in mice treated simultaneously with antibodies to CD4 and CD8 antigens, whereas either CD4, CD8, or NK1.1 antibody alone was ineffective. Analysis of the cellular mechanism involved in the antimetastatic activity revealed the involvement of a tumor-associated antigen-specific delayed-type hypersensitivity response. These data suggest that the life-prolonging effect of the combination of lentinan and IL-2 is mediated by antigen-specific T cells and that the combination of pre- and post-operative therapy with lentinan and IL-2 may be effective to prevent cancer recurrence and metastasis after surgical resection.

Animals↗