Search PubMed⌕ Search

Biomedical subjects

M Sunagawa

Publications and source records attributed to M Sunagawa.

At least 73 records · Page 4Linked to original sources
PubMed1996

Powerful immunosuppression by a new 40-kd serum protein (KX-5) induced by liver transplantation.

The presence of novel immunosuppressive proteins in the serum of liver grafted rats is associated with the induction of tolerance. This may provide part of the explanation for the induction or maintenance of tolerance in this liver graft mode, although their relationship to the antigen-specific aspects of liver graft survival (clonal deletion of T cells, release of soluble class I antigen, production of anti-class II antibodies) remains to be investigated. The KX-5 protein was nonspecifically immunosuppressive in vivo, suggesting the possibility of harnessing the tolerogenic properties of liver grafts in a soluble form for clinical application.

Animals↗
PubMed1995

Pharmacokinetics of habutobin in rabbits.

Following the administration of habutobin, the fibrinogen level in the circulating blood of the rabbits decreased. These results showed that the activity of habutobin was retained in vivo. The plasma level of habutobin was determined by a ELISA-double sandwich method. The pharmacokinetics of habutobin from Trimeresurus flavoviridis venom was studied in rabbits following i.v. administration of 50 micrograms kg-1 of habutobin. The time course of the plasma concentration of habutobin fitted a two-compartment open model. The half-life of the distribution phase was 4.43 +/- 1.28 min and that of the elimination phase was 50.42 +/- 7.89 min. The area under the plasma concentration-time curve (AUC) was 38.69 +/- 6.68 micrograms min ml-1. The total body clearance was 3.82 +/- 1.08 ml min-1. When the steady state was reached, the concentration ratio of habutobin in the tissue (Ct) to that in the plasma (Cc), Ct:Cc was 0.47:1. These findings suggest that relatively little habutobin tended to remain in the tissue.

Animals↗
PubMed1995

Isolation of a 40 kDa immunoinhibitory protein induced by rat liver transplantation.

In certain combinations of donor and recipient rat strains, such as DA (RT1a) donors into PVG (RT1c) recipients, rejection after orthotopic liver transplantation (OLT) is overcome without immunosuppressive drugs, although other organs transplanted between these combinations are promptly rejected. The mechanisms involved in achieving drug-free liver allograft tolerance still remain poorly understood. In the present study, OLT (DA into PVG) serum from various postoperative times was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and two unique proteins of 40 kDa and 37 kDa were found to be in large concentrations in 60 day post-OLT serum. These proteins could only be detected at specific times after OLT in the DA into PVG combination and could not be detected in the serum of syngenically transplanted animals (DA into DA) and (PVG into PVG), rejector combinations (DA into LEW) requiring immunosuppressive treatment or induced by other organ transplants. When these proteins were purified and sequenced they were found to have an identical N-terminal sequence which is not listed in sequence databases. Mixed lymphocyte assays revealed that only the 40 kDa protein has a immunosuppressive capability which additionally appears to be donor specific. The 40 kDa protein will aid further in the understanding of how drug-free tolerance is attained in certain liver allografts and may also act as a marker of when treatment with conventional immunosuppressive drugs can be stopped in clinical OLT providing a homologue of the molecule can be found. This possibility appears likely as case reports already exist of patients who have successfully been able to cease treatment with such drugs.

Amino Acid Sequence↗
PubMed1995

Stability of a 1 beta-methylcarbapenem antibiotic, meropenem (SM-7338) in aqueous solution.

The stability and the degradation products of 1 beta-methylcarbapenem, meropenem in aqueous solution were investigated. In pH 4-8 dilute solution, pseudo-first-order degradation was observed, and good stability of meropenem in aqueous solution was demonstrated by the effect of 1 beta-methyl group against hydrolysis of beta-lactam ring. As degradation products, the beta-lactam hydrolyzed product and the dimer product resulting from intermolecular aminolysis of beta-lactam ring by the amine of the second molecule were described.

Anti-Infective Agents↗
PubMed1995

Plasminogen activators in tissue extract of aural cholesteatoma.

Using a biochemical technique, the authors characterized and identified the plasminogen activator (PA) derived from tissue extracts of six aural cholesteatomas. The results of fibrin zymography indicated that the tissue extracts of two cholesteatomas demonstrated two lytic zones on fibrin-agarose plates. One of the lytic zones was at about 72 kd, while the other zone was at about 64 kd. Using various goat immunoglobulin G (IgG)-containing antibodies (anti-human uterine tissue type PA (t-PA), anti-human low-molecular-weight (LMW) urokinase, and nonspecific goat IgG) and plasminogen-free fibrin-agarose plates, we confirmed that the cholesteatoma tissue extracts contained 72 kd t-PA and 64 kd urokinase type PA (u-PA). Furthermore, we measured the t-PA and u-PA activities in the tissue extracts selectively by parabolic rate assay. In order to estimate the PA activity, we developed optimal conditions for this assay. The specific t-PA activity ranged from 0.03 to 0.43 mIU/micrograms-protein and the specific u-PA activity ranged from 0 to 0.35 mIU/microgram-protein. The highest percentage of u-PA with respect to the total PA activity was 44.9%. However, in four of the six cases, we failed to detect u-PA activity. In the present study, we thus clarified the presence of PAs in tissue extracts of aural cholesteatomas. Furthermore, we confirmed that measureable u-PA occurred in some tissue extracts. We anticipate that the u-PA in inflammatory tissues plays an important role in the degradation of the extracellular matrix via the formation of plasmin and collagenases.

Cholesteatoma, Middle Ear↗
PubMed1995

Structural features resulting in convulsive activity of carbapenem compounds: effect of C-2 side chain.

The neurotoxicity of meropenem was much lower than that of both imipenem and panipenem after intraventricular administration to mice. To clarify the major structural features responsible for the induction of convulsions by carbapenem antibiotics, the structure-activity relationship on convulsant activity was investigated in N-acetyl-2-pyrroline and cyclopentene derivatives which correspond to the 5-membered ring containing the C-2 side chain of carbapenem antibiotics. Among these derivatives, compounds with strong basicity in the side chain showed convulsant activity similar to that of the parent carbapenem compounds. In addition to the strength of the basicity of the amino group, the distance from the carboxyl to the amino group and steric crowding around the amino group also appeared to play an important role in the induction of convulsions. The results of gamma aminobutyric acid (GABAA) receptor binding assays indicated that the induction of convulsions was caused predominantly by the inhibition of GABAA-mediated inhibitory transmission. However, the in vivo convulsant activity of some of these compounds did not correlate with their in vitro inhibitory effect on GABAA receptor binding.

Animals↗
PubMed1995

[Neoadjuvant chemotherapy with tegafur suppository for rectal cancer--effects of tegafur on nuclear DNA content of cancer cells--Tochigi Colorectal Cancer Study Group].

To assess the significance of neoadjuvant chemotherapy for large bowel cancer, we investigated an effect of tegafur on cancer cell kinetics by DNA content flow cytometric analysis. The pathologic specimens analyzed in this study were obtained from 28 patients with rectal cancer who had received tegafur suppositories prior to surgery. Mean cumulative doses administered were 13.4 g, and mean duration was 12.7 days. In 24 of the 28 specimens, the DNA ploidy and DNA index of the cancer cells were essentially unchanged after the chemotherapy, and DNA aneuploidy was present in 67%. The proportion of cells in S-phase in DNA aneuploid tumors was significantly higher than in DNA diploid tumors. The proportion of cells in G0G1-phase was inversely correlated to that in S-phase. After the chemotherapy, the proportions of cells in S-phase increased both in DNA diploid and aneuploid tumors, although a significantly higher mean value was found only for the latter (p < 0.05). In the DNA aneuploid tumors, there was a higher frequency of responders confirmed by histological evaluation (44%) as compared to the DNA diploid tumors (25%), and a tendency for increases in S-phase fraction of the responders to be greater than in non-responders. These results suggest that DNA flow cytometry-derived parameters may conceivably be useful in predicting the antitumor effect of 5-FU and its derivatives against large bowel cancer.

Aged↗
PubMed1995

[An immunohistochemical study on microtubule associated protein-1 of normal and malignant human gastric tissue].

Microtubule Associated Protein-1 (MAP-1) plays an important role for polymerization of tublin to microtubules. Indirect immunohistochemistry using anti-MAP-1 monoclonal antibody was performed in this study. Difference of internuclear MAP-1 staining patterns between normal and malignant human gastric tissues was investigated. Normal gastric tissue had localized MAP-1 positive staining nucleus in corresponding area of generative cell zone of gastric gland. On the other hand, the 75% cases of gastric cancer showed numerous labeled nuclei in most of the cancer tissues, and 25% cases did not show positive staining of nuclei in cancer tissue. The nuclei staining were classified as negative (-), weak granular (+) and strong punctate (++). The tissue staining pattern was fallen into two patterns, uniform and ununiform stained groups. Positive nuclei staining for MAP-1 and staining pattern had no correlation with histological type of gastric cancer, vessel invasion and lymph node metastasis. But post operative 5-years survival rares were 77.3% in uniform stained group and 30.0% in ununiform stained group. Thus, there were relationship between the post operative survival ratio and the staining pattern of nuclei. Internuclear MAP-1 staining pattern was considered to be one of effective parameters on prognostic sign in gastric cancer.

Antibodies, Monoclonal↗
PubMed1995

Effect of argatroban on the formation of artificial thrombus on dogs.

In the present study, we have investigated the effects of a synthetic antithrombin, Argatroban, and an antiplatelet agent. Ticlopidine hydrochloride, on the weight of artificial thrombus. These drugs at various concentrations were added to canine bloods, which were adjusted to 20%, 40% and 60% of haematocrit, and an artificial thrombus was formed using a modification of Chandler's method. Argatroban inhibited the formation of artificial thrombus, and this marked inhibition was observed especially in the experiment using blood with a high value of Ht. On the other hand, Ticlopidine hydrochloride did not inhibit the formation of artificial thrombus. From these results, it becomes clear that the mechanism of inhibitory action of Argatroban on artificial thrombus formation is based on the inhibition of thrombin activity and not on the inhibition of platelet aggregation. In addition, it is suggested that Argatroban inhibits the aggregation of red blood cells in the manner of direct or indirect action.

Animals↗
PubMed1994

Role of DNA ploidy patterns in esophageal squamous cell carcinoma. An ultraviolet microspectrophotometric study.

BACKGROUND: Controversy still exists about the influence of DNA content on the prognosis for patients with esophageal squamous cell carcinoma. METHODS: DNA ploidy was determined by microspectrophotometric (MSPM) analysis of paraffin embedded malignant tissue from 78 patients with squamous cell carcinoma of the esophagus. The DNA distribution pattern was classified as diploid, low grade aneuploid (LGA), and high grade aneuploid (HGA) pattern. The relationships among DNA distribution patterns, pathologic features, clinical findings, and prognoses were investigated. Twenty-seven of 78 patients were also selected for analyses of the DNA ploidy pattern of lymph node metastases. RESULTS: Of 78 cancers, 20 (26%) were diploid, 15 (19%) LGA, and 43 (55%) HGA. The advanced carcinomas had the higher distribution of HGA pattern (55%), whereas the diploid pattern was more frequent in early stage (70%) or superficial (65%) esophageal cancer. In patients with the HGA pattern, there was a significantly higher frequency of lymph node metastases (79%) and marked lymphatic (74.4%) and vascular (69.8%) invasion compared with those exhibiting the LGA (33.3%) or diploid (25%) pattern. Five-year survival rates for patients with diploid carcinoma (57%) was significantly better than for those with the HGA pattern (14%). The distribution of nuclear DNA content was much narrower in the metastatic lymph node than in the corresponding primary cases. CONCLUSIONS: The HGA of DNA pattern based on spectrophotometry closely correlated with the factors generally indicative of the aggressive behavior of malignant tumors. Therefore, the role of the DNA ploidy pattern as a prognostic factor was emphasized.

Aged↗