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Biomedical subjects

T Matsuno

Publications and source records attributed to T Matsuno.

At least 55 records · Page 3Linked to original sources

Cytokine-inducing activity and antitumor effect of a liposome-incorporated interferon-gamma-inducing molecule derived from OK-432, a streptococcal preparation.

An interferon-gamma (IFN-gamma)-inducing molecule (OK-PSA) has been purified from OK-432 by an affinity chromatographic technique performed on cyanogen bromide-activated Sepharose 4B-bound TS-2 monoclonal antibody, which neutralizes IFN-gamma-inducing activity of OK-432. OK-PSA has striking anti-tumor activity in vivo and in vitro. In the current study, the liposomes were used to improve the delivery of the agent (OK-PSA) to effector cells and to increase the therapeutic effect. Significantly less OK-PSA encapsulated into liposomes (Lipo-OK-PSA) than OK-PSA alone (1/100 or less of OK-PSA alone) was required to induce IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, interleukin-1 beta (IL-1 beta), natural killer, and lymphokine-activated killer activities by human peripheral blood mononuclear cells and mouse spleen cells. Furthermore, higher levels of these activities were detected in peripheral blood mononuclear cells and mouse spleen cells treated with Lipo-OK-PSA than in those treated with OK-PSA. All of these activities induced by Lipo-OK-PSA were almost completely neutralized by anti-asialo-GM1 antibody and complement (p < 0.001). In in vivo experiments, Lipo-OK-PSA elicited striking anti-tumor activity on syngeneic Meth-A tumor-bearing and colon 26-bearing BALB/c mice and on salivary gland tumor-bearing nude mice far better than did OK-PSA. Furthermore, high levels of natural killer and lymphokine-activated killer activities and a significant increase in the number of cells positive for asialo-GM1, IFN-gamma, TNF-alpha, or IL-1 beta were detected in the spleen cells derived from the animals given Lipo-OK-PSA compared with those given saline. These findings clearly indicate that OK-PSA plays an important role in the anti-tumor efficiency of OK-432, and that, for the most part, liposome encapsulation of this molecule markedly accelerates its effect mediated by asialo-GM1-positive cells (mainly natural killer cells).

Adenocarcinoma↗

Bipolar hemiarthroplasty for osteonecrosis of the femoral head. A 7- to 18-year followup.

This study evaluated clinical and radiographic results of bipolar hemiarthroplasties for the treatment of osteonecrosis of the femoral head. Forty-eight hips in 35 patients with a mean age of 37 years who underwent primary bipolar hemiarthroplasties were observed for an average of 11.4 years. Osteonecrosis was associated with corticosteroid use (21 patients), alcohol (six patients), idiopathic (four patients), and other conditions (four patients). The average Harris hip score was 46 before surgery and 86 at the time of the final followup. Twenty (42%) hips were radiographic failures, and 12 (25%) hips were revised. Groin symptoms were present in 20 (42%) hips. Radiographic proximal migration greater than 4 mm and osteoarthritic signs of the acetabulum indicated a high risk of groin symptoms. The results were inferior to those previously reported for total hip arthroplasty. Thus, for the treatment of osteonecrosis of the femoral head in which necrotic lesions are wide, the authors no longer use this system and currently use total hip arthroplasty.

Adult↗

Acetabular development after reduction in developmental dislocation of the hip.

A radiologic study was conducted on 56 patients with developmental dislocation of the hip (63 hips). Fifty hips in which neither acetabular nor femoral osteotomy was performed were classified as satisfactory (Severin Groups I and II) or unsatisfactory (Severin Groups III and IV) based on radiographs when growth was completed. The sequential changes in the center edge angle and the acetabular index were compared when the patients were ages of 5, 10, and 15 years. There was a significant relationship between the center edge angle and the acetabular index when the patients were 5 years of age and at final outcome. Most (85.7%) patients with a center edge angle less than 8 degrees and an acetabular index greater than 26 degrees at 5 years of age eventually were classified as Severin Groups III and IV at skeletal maturity. These findings suggest that radiologic results at the time when growth is completed can be predicted based on the center edge angle and the acetabular index in radiologic measurements at 5 years of age. The authors recommend that if at 5 years of age the center edge angle is less than 8 degrees and the acetabular index is greater than 26 degrees, consideration be given to an osteotomy to bring these values to a more normal range to improve final outcome.

Acetabulum↗

Multiple tumors and a novel E2F-4 mutation. A case report.

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.

Adult↗

Synthesis and antitumor activity of benzimidazolyl-1,3,5-triazine and benzimidazolylpyrimidine derivatives.

Triamino-substituted 1,3,5-triazine and pyrimidine derivatives were synthesized and tested for antitumor activities using some human cancer cell lines and murine leukemia cell lines. All the compounds having benzimidazolyl and morpholino groups as substituents on the 1,3,5-triazine ring showed antitumor activity. Pyrimidine derivatives having the same groups as substituents also showed antitumor activity. Among them, the compounds having 1-benzimidazolyl, morpholino and cis-2,3-dimethylmorpholino groups as substituents on the 1,3,5-triazine ring or pyrimidine ring exhibited the most potent antitumor activity, and these compounds exhibited no or very weak aromatase inhibitory activity. In contrast, the compounds having imidazolyl group instead of benzimidazolyl group as a substituent on the 1,3,5-triazine ring showed a potent aromatase inhibitory activity.

Animals↗

Cemented total hip arthroplasty with autogenous acetabular bone grafting for hips with developmental dysplasia in adults: the results at a minimum of ten years.

We carried out primary cemented total hip arthroplasty (THA) on 25 hips in 21 patients with developmental dysplasia of the hip, using autogenous acetabular bone grafts. The socket was placed at the level of the true acetabulum and bone from the femoral neck was used as graft. Five hips were excluded, leaving 20 which were followed up for a mean of 12.9 years (10 to 18). The mean modified Merle d'Aubigné and Postel functional scores were 5.6 for pain, 4.3 for mobility and 4.2 for range of movement. Radiological examination showed aseptic loosening in three sockets but not in the stems. The bone grafts had united and showed no evidence of late failure.

Adult↗

[A case of nonresectable scirrhous type gastric cancer successfully treated by low-dose cisplatin (CDDP), 5-fluorouracil (5-FU) and pirarubicin (THP)].

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy based on the concept of biochemical modulation has been reported. For example sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year-old man who was suffering from scirrhous type gastric cancer with pyloric stenosis was treated with this regimen. Eight weeks after the start of therapy, his gastric capacity and lumen diameter had clearly increased, and he was taking ordinary meals. Ascites had also completely disappeared. CR has now been continued about 7 months. This regimen is considered to be promising for scirrhous type gastric cancers with a poor prognosis.

Adenocarcinoma, Scirrhous↗

Induction of donor-specific hyporesponsiveness and prolongation of cardiac allograft survival by jejunal administration of donor splenocytes.

BACKGROUND: Donor-specific immunosuppression is important in transplantation surgery. We examined the immunosuppressive effects of donor splenocytes administered postoperatively into the jejunum and the effect of such treatment on the survival of heterotopic vascularized cardiac allograft in rats. METHODS: Lewis (LEW, RT-1l) recipient rats were treated with 5x10(7) Brown Norway (BN, RT-1n) donor splenocytes for 5 days orally, intrajejunally, or subcutaneously. The immune responses of LEW treated with either donor BN or irrelevant Wistar King A (WKA, RT-1k) were examined by mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH). The effect of postoperative enteral treatment for 6 days with suboptimal dose of cyclosporine (CsA) on heterotopic cardiac allotransplantation was investigated. We measured the production of cytokines (interleukin [IL]-2, IL-4, IL-10, and interferon-gamma [IFN-gamma]) in the supernatant of MLR by ELISA. The effect of intravenous dose of GdCls to block Kupffer cell function was also investigated before the administration of splenocytes. RESULTS: MLR and DTH responses were strongly inhibited in a BN-restricted manner after jejunal or oral feeding of donor BN splenocytes but not by subcutaneous injection or injections by any routs of WKA splenocytes. The effect was more prominent in jejunal than oral feeding. Immunosuppression was associated with a significant inhibition of IL-2 and IFN-gamma production and increased concentrations of IL-4 and IL-10 in MLR supernatants. Immunosuppression was abrogated by pretreatment with GdCl3. Postoperative intrajejunal feeding of donor splenocytes with CsA significantly prolonged cardiac allograft survival time (18.7+/-7.3 vs. 9.9+/-1.7 days for control animals). CONCLUSION: Jejunal administration of splenocytes produces donor-specific immunosuppression and prolongs cardiac allograft survival. Our results suggest the involvement of T helper (Th) 2 cytokines and Kupffer cells in the induction of immune hyporesponsiveness, and indicate that this method represents a unique approach for induction of donor-specific immunosuppression.

Animals↗

Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver.

BACKGROUND: Although inhibition of endothelial nitric oxide synthase (eNOS) has been reported to aggravate hepatic ischemia-reperfusion (I/R) injury, the role of inducible nitric oxide synthase (iNOS) has been still unknown. We investigated the role of NO produced by iNOS, and evaluated the effect of an iNOS inhibitor on prolonged warm I/R injury in the pig liver. METHODS: Pigs were subjected to 120 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in serum and hepatic microdialysate NO2- + NO3- (NOx) and the cellular distribution of eNOS and iNOS by immunohistochemistry, including a double-immunofluorescence technique in combination with confocal laser scanning microscopy. The effect of iNOS inhibitor was also investigated. RESULTS: Hepatic I/R induced new nitric oxide production in serum and hepatic microdialysate NOx after reperfusion and severe hepatic damage in the centrilobular region where nitrotyrosine was strongly expressed. Diffuse eNOS expression in sinusoidal endothelium did not differ before and after reperfusion. In contrast, strong iNOS expression in Kupffer cells and neutrophils appeared strongly in the centrilobular region after reperfusion. Pigs with intraportal administration of N(G)-nitro-L-arginine (10 mg/kg) died during the period of ischemia or early in the period of reperfusion with a high mortality rate (80.0%). Intraportal administration of aminoguanidine hemisulfate (10 mg/kg) significantly suppressed nitric oxide production and serum aspartate aminotransferase after reperfusion, inhibited nitrotyrosine expression, and attenuated hepatic damage. CONCLUSIONS: These results indicate that hepatic I/R injury is triggered by centrilobular iNOS expression; and attenuated by inhibition of iNOS.

Animals↗

Osteonecrosis of the femoral head. Simple varus intertrochanteric osteotomy.

We present the long-term results of simple varus intertrochanteric osteotomy for osteonecrosis of the femoral head. We followed 26 hips in 20 patients, with a mean age at the time of surgery of 36 years, for a mean of 12.5 years. The mean varus angulation was 23 degrees. The outcome in 19 of the hips (73%) was good or excellent; seven (27%) had a fair or poor result, with four needing some form of prosthetic arthroplasty. Simple varus intertrochanteric osteotomy is indicated, even if the extent of the capital infarct comprises more than 50% of the diameter of maximum radial distance from the circumference, provided that after operation the medial necrotic lesion measures less than two-thirds of the weight-bearing area, and the superolateral bone is normal.

Adult↗

Peripheral mononeuropathy induced by loose ligation of the sciatic nerve in the rat: behavioral, electrophysiological and histopathologic studies.

The relationship between clinical parameters and pathological changes was investigated in an animal model of mononeuropathy, by behavioral, electrophysiological and histopathological methods. Mononeuropathy was induced in rats by loosely tying ligatures around the sciatic nerve. Eighty-four rats were used, and these were divided into fourteen groups to determine chronological changes in the withdrawal reflex latency, nerve conduction velocity and ultrastructure of the nerve from 1 to 84 days after nerve ligation surgery. Pathological changes around the ligated nerves were divisible in three phases: the first week was an inflammatory phase, when axonal degeneration, phagocyte infiltration and interstitial edematous changes were observed. The second and third weeks were a nerve-sprouting phase, when numerous axonal sprouts and remyelination were seen. The fourth to twelfth weeks were a recovery phase in which maturing myelination and interstitial fibrosis were characteristic. In the inflammatory phase, withdrawal reflex latencies were shortened, and sensory nerve conduction velocities (SCV) and motor nerve conduction velocities (MCV) gradually decreased. In the nerve-sprouting phase, the latency values remained low, and SCV and MCV were minimal. The parameters examined gradually returned to control levels during the recovery phase. In conclusion, these findings increase the knowledge of disease progression in mononeuropathy with hyperalgesia in human and animal models.

Animals↗

Minimum 10-year results of Sugioka's osteotomy for femoral head osteonecrosis.

Sugioka's transtrochanteric rotational osteotomy was performed on 14 hips (12 patients) before 1987 for avascular necrosis of the femoral head involving a large part of the weight-bearing area. Three hips required a secondary total hip arthroplasty within 5 years after the osteotomy. The remaining 11 hips were examined at a mean of 13.2 years after surgery (range, 10-17.7 years). The clinical and radiologic results were related to the preoperative radiographic stage of the disease. In the hips with less than 2 mm of collapse, highly satisfactory results were maintained more than 15 years after surgery, with minimal development of degenerative changes. In hips with 2 mm or more of collapse or with acetabular changes, the results tended to deteriorate gradually during the long course of observation but were fairly acceptable. This study shows the osteotomy can enable hip joints to survive and function well for more than 10 years with proper patient selection and operative procedure.

Adult↗