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Biomedical subjects

T Tsujinaka

Publications and source records attributed to T Tsujinaka.

At least 73 records · Page 4Linked to original sources
PubMed1995

Muscle undergoes atrophy in association with increase of lysosomal cathepsin activity in interleukin-6 transgenic mouse.

Interleukin(IL)-6 transgenic mice were produced by microinjection of human IL-6 cDNA fused with H-2Ld promoter into the pronucleus of fertilized eggs from C57BL/6J mice. At 16 weeks old, the gastrocnemius muscles of the IL-6 transgenic mice became atrophic as compared to those of the normal mice, while the body weights increased significantly. The activities and mRNA levels of lysosomal cathepsins B and L were increased in the muscles of the transgenic mice. Immunohistochemical study on the muscles showed increased staining of both cathepsins B and L in the transgenic mice. IL-6 is responsible for enhanced muscle catabolism by activating the lysosomal cathepsin (B and L) system.

Animals↗
PubMed1995

Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy for inoperable squamous cell carcinoma of the esophagus potentially followed by surgery.

Twenty-four previously untreated patients with primary inoperable squamous cell carcinoma of the esophagus showing no evidence of hematogenous metastasis were treated with concurrent chemotherapy and radiation therapy (CRT) followed by surgical resection if possible. The chemotherapy regimen consisted of 5-fluorouracil 750 mg/m2 on days 1-4 and 21-24, and cisplatin 70 mg/m2 on days 1 and 21. Radiation therapy was administered over days 1-26 (200 cGy/day five times per week with an initial planned dose of 40 Gy). Five patients (8%) showed complete response (CR), 14 patients (58%) had partial response (PR), and 19 had good local control (CR 2, PR 17). Eleven cases (48%) underwent esophageal resection with no operative mortality. Curative resection was accomplished in eight cases (35%). Toxicities observed in CRT were leukopenia (grades 3 and 4) 38%, nausea and vomiting (grades 2 and 3) 67%, esophagitis 42%, and fever 42%. The median survival time (MST) for 11 neoadjuvant cases was 349 days (P < 0.05) compared to 212 days for palliative treatment (six cases) and 126 days for no treatment (six cases) after CRT. The MST of eight patients who received curative resection had not been reached after a 17-month median follow-up time. Concurrent chemotherapy with 5-fluorouracil plus cisplatin and radiation proved to be a safe regimen yielding a satisfactory response and minimal toxicity in this particular group of patients. Extensive surgery was thus determined to be feasible after CRT and to contribute to prolonging survival.

Aged↗
PubMed1995

Change of flow cytometric DNA content in para-aortic lymph node showing recurrence after adjuvant chemotherapy for gastric cancer.

A para-aortic lymph node showing recurrence was resected from a patient who had received adjuvant chemotherapy after curative resection of an advanced gastric cancer. A flow cytometric analysis of DNA content was carried out for the primary lesion, a metastatic lymph node and the resected lymph node. A peri-diploid cell population in addition to diploid cells appeared in the recurrent lesion, whereas a major diploid cell population and a minor aneuploid cell population were found in the primary lesion and the metastatic lymph node, indicating that a clone of chemo-resistant tumor cells selectively multiplied after the cytotoxic therapy. The characters of a recurrent lesion may be changed by clonal selection following chemotherapy.

Adenocarcinoma↗
PubMed1995

Interleukin-6 induces proteolysis by activating intracellular proteases (cathepsins B and L, proteasome) in C2C12 myotubes.

1. A cell culture system of C2C12 myotubes was established as a model of the muscle. With the aid of this model, the half-lives of intracellular proteins as well as the activities and mRNA levels of proteasomes (26S and 20S) and cathepsins (B, L, and H) were examined in the presence of various amounts of cytokines. 2. It was found that 100 units/ml recombinant human interleukin-6 somewhat shortened the half-life of long-lived proteins to 23.79 +/- 1.55 h (control: 25.60 +/- 1.87 h). When 1% fetal bovine serum contained in the culture medium was replaced by 0.5 mg/ml bovine serum albumin, interleukin-6 was more effective since 10 units/ml of interleukin-6 shortened the half-life to 19.09 +/- 2.87 h (control: 22.26 +/- 321 h). Interleukin-6 (100 units/ml) increased the activity of 26S proteasome by 31.5%, of cathepsin B by 53.5% and of cathepsin B+L by 21.3%. These increases occurred in association with an increase in their transcription. 3. On the other hand, 1000 units/ml of recombinant human tumour necrosis factor alpha prolonged the half-life of long-lived proteins while reducing the protease activities of 20S proteasome (-27.1%), cathepsins B (-64.6%) and B+L (-54.9%). 4. These results suggest that interleukin-6 induces degradation of long-lived intracellular proteins by activating both the non-lysosomal (proteasomes) and lysosomal (cathepsins) proteolytic pathways. It is therefore concluded that interleukin-6 is a candidate for a proteolysis-inducing factor in myotubes and may play an important role in the progression of muscle degradation in systemic inflammatory responses induced by sepsis or severe injury.

Animals↗
PubMed1995

Changes of proteasomes and cathepsins activities and their expression during differentiation of C2C12 myoblasts.

C2C12 myoblasts fuse to form multinucleated myotubes and express muscle specific proteins during differentiation. To elucidate developmental regulation of intracellular proteolytic systems, enzymatic activities, protein and mRNA levels of proteasomes (20S and 26S) and lysosomal cathepsins (B, L, and H) were examined. Myoblasts were differentiated fully to myotubes 6 days after starting differentiation. In this developmental process, the 26S proteasome activity decreased, while the 20S proteasome activity increased. Expression of proteasome subunits of 20S (RC2, RC8) and regulatory components of 26S (S4, S7) was down-regulated, though total protein levels of proteasomes showed no remarkable changes. On the other hand, enzymatic activities of cathepsins B and B + L increased in association with an increase of their transcriptional and translational levels. Expression of their specific endogenous inhibitor, cystatin beta, also increased. Maturation of the lysosomal proteolytic system was tightly linked to the differentiation process. These results suggested that signals for differentiation of myoblasts mediate a change of intracellular proteolytic systems, involving up-regulation of lysosomal cathepsins and down-regulation of proteasomes.

Animals↗
PubMed1995

Modulation of muscle protein metabolism in disseminated intravascular coagulation.

Muscle protein degradation and intracellular protease activities were investigated in disseminated intravascular coagulation (DIC), which is frequently associated with severe catabolic states such as sepsis and multiple organ failure. DIC was introduced in rats by repeated intravenous thrombin injections. Saline was injected in control rats. In the 28 rats (14 with DIC and 14 controls), the bilateral soleus (SOL) muscles were incubated in an oxygenated medium without cycloheximide (CH) to determine the release of tyrosine (Tyr) into the incubated medium. From 24 rats (12 with DIC and 12 controls), the SOL and extensor digitorum longus (EDL) muscles were harvested to measure the activities of proteasome and of cathepsins L and B. The contralateral muscles were incubated in a medium with 0.5 mM CH to determine the release of Tyr and 3-methylhistidine (3-MH). The release of Tyr without CH (net proteolysis) from SOL muscles with DIC was greater than in controls (218 +/- 83.3 vs. 145 +/- 47.7 pmol/mg/h. However, the release of Tyr and 3-MH with CH (total proteolysis) and the activities of proteasome and cathepsins in DIC were nearly the same as those in controls. In both DIC and control rats, the total release of Tyr and proteasome activity were greater in SOL than in EDL muscles. These results suggest that reutilization of Tyr, reflecting protein synthesis, is suppressed in DIC and that the red slow muscle is more active in nonfibrillar proteolysis than the white fast muscle.

Animals↗
PubMed1995

[Study on therapeutics adopted after occlusion of intraarterial reservoir in patients with liver tumor].

Over the last 5 years, we experienced thirty-nine patients with liver tumors undergoing implantation of an intraarterial reservoir through the gastroduodenal artery. Nine of the 39 patients had hepatocellular carcinomas, while the rest had metastatic liver tumors. In 32 patients, intraarterial chemotherapy via an implanted reservoir was discontinued either because of death in 20 patients with an average survival period of 11.7 months or because of occlusion of an intraarterial line in 12 patients with an average treatment period of 20.2 months. Regarding treatment modalities adopted for intraarterial therapy, transcatheter arterial embolization, surgical resection, microwave tumor coagulation, ethanol injection therapy, and a subselective intraarterial chemotherapy were performed in 3 patients with hepatocellular carcinomas. All of them survived more than 2 years after disuse of the reservoir. Out of 5 patients with metastatic liver tumors of colorectal cancer, one patient underwent additional surgical resection, two patients had no therapy who survived only two or three months, and two patients were still alive without additional therapies. Of four patients with metastatic liver tumors, 3 from breast cancer and one from leiomyosarcoma of stomach were treated with systemic chemotherapy or subselective intraarterial chemotherapy combined with radiation therapy. The average survival period of these 12 patients was 16.2 months, and 7 of them are still alive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Long-term survival in two cases of multiple liver metastasis successfully treated with intraoperative ultrasound-guided microwave tumor coagulation (MTC)].

Since April 1990, multiple metastatic liver tumors have been treated with intraoperative ultrasound-guided microwave tumor coagulation (MTC) in combination with postoperative intraarterial chemotherapy. Twenty-four patients have been enrolled in this therapeutic modality and two of five patients treated in 1990 achieved long-term survival. In case 1, a 67-year-old woman was diagnosed as bearing gastric leiomyosarcoma with multiple liver metastasis. Total gastrectomy was performed, and six hepatic lesions were treated by MTC along with implantation of an intraarterial reservoir. Postoperative intraarterial chemotherapy was administered in a selective or subselective manner. Her survival time was 4 years and 6 months. In case 2, a 47-year-old man was diagnosed as having liver metastasis from descending colon cancer 1 year and 5 months after left hemicolectomy. When he was laparotomized for the treatment of adhesive ileus, three metastatic liver tumors were treated with MTC. Afterward, he underwent hepatic resection, intraarterial and intraportal chemotherapy. He survived for 5 years and 5 months after being diagnosed with liver metastasis. MTC is one of the useful modalities for the treatment of multiple liver metastasis.

Aged↗
PubMed1994

Tumor-derived components were responsible for suppression of ornithine decarboxylase activity in the rat wounded skin.

To elucidate the principal cause of delayed wound healing in a tumor-bearing host, the effect of Yoshida sarcoma-derived components on dermal wound healing was investigated in rats with the aid of ornithine decarboxylase (ODC) activity and in vivo bromodeoxyuridine (BrdU) labeling index. The ODC activity in the wounded skin decreased 3 and 7 days after intraperitoneal inoculation of Yoshida sarcoma cells (378.0 +/- 37.3 on Day 3, 280.0 +/- 140.0 on Day 7 vs. 809.3 +/- 109.5 pmol/mg protein/hour on Day 0). When administered 24 hours before and immediately after wounding, the crude nuclear component of the tumor cells significantly decreased the ODC activity in the wounded skin as compared with the control (185.9 +/- 159.8 vs. 534.0 +/- 59.1), but the non-nuclear component was not effective. When nuclear extracts of Yoshida sarcoma cells were intraperitoneally administered immediately after wounding, the 0.15 M or 0.35 M NaCl extract significantly suppressed ODC activity in the wounded skin (233.5 +/- 14.5 and 352.3 +/- 63.2 pmol/mg protein/hour, respectively) in comparison to the control (445.9 +/- 73.6). The BrdU labeling index of epidermal basal cells adjacent to the edge of the wound decreased up to 52% of the control by injection of the 0.15 M extract. It seems that tumor-derived nuclear components may be responsible for delayed wound healing which is commonly observed in cancer cachexia.

Animals↗
PubMed1994

Role of intracellular proteases in differentiation of L6 myoblast cells.

The activities of cathepsins B, L, and H increased by 3.0, 2.3, and 1.9 fold in differentiation of L6 myoblasts. Separating from the intrinsic inhibitor, both mu- and m-calpain activities also increased by 4.9 and 1.7 fold during differentiation. Calpeptin (10(-5)M), cell penetrating calpain inhibitor, blocked fusion of myoblast by 55% and increment of creatine phosphokinase (CPK) activity by 20.3% with inhibiting the activities of cathepsin L and mu-calpain. E-64(10(-4)M) did not block fusion of myoblasts but increment of CPK activity by 25.0% with inhibiting the activities of cathepsin L and B. Calpain may be involved in the process of myoblast fusion.

Animals↗
PubMed1994

[A multi-institutional study for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery].

A multi-institutional study was conducted for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery. Forty five cases including thirty six complete cases were entered basing on the diagnostic criteria and the mortality of complete cases was 17%. By the administration of miconazole (MCZ), clinical response rate was obtained in 87%, mycological radiation rate in 82% and valuable rate in 71%, with occurrence of side effects in 20%. Fungal endophthalmitis was found in 41% (12/29 cases). beta-glucan [the toxinometer method (T), the Seikagaku-Kogyo method (S)] and candida antigen [the C and-Tec method (C)] were monitored as sero-diagnostic methods, the positive rates for all cases, fungemia, and mycosis of which were 63, 83, 62% (T), 88, 100, 92% (S) and 52, 83, 50% (C), respectively. After mycological re-classification, the positive rates of the T method and endophthalmitis, and the mortality rates were 86, 60, 38% in fungemia, 63, 43, 23% in urinary tract infection, 64, 80, 7% in TPN infection, and 33, 17, 33% in drain infection, respectively. High association of endophthalmitis was found in TPN infection. The beta-glucan assay and a prospective ophthalmoscopic examination are useful for the early diagnosis of deep fungal infection and it is reasonable to treat patients in gastrointestinal surgery by MCZ when mycosis is confirmed or suspected.

Digestive System Surgical Procedures↗
PubMed1993

Fibrinogen Osaka IV: a congenital dysfibrinogenemia found in a patient originally reported in relation to surgery, now defined to have an A alpha arginine-16 to histidine substitution.

We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43-46). Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A alpha chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the "A" site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A alpha arginine-16 to histidine substitution identified among Japanese families.

Afibrinogenemia↗
PubMed1993

Effect of indomethacin on postoperative protein metabolism after gastrectomy under total parenteral nutrition.

A randomized trial was undertaken to evaluate the effects of postoperative indomethacin (IDM) administration on protein metabolism in 20 patients who underwent an uncomplicated distal gastrectomy and were placed on post-operative total parenteral nutrition (TPN). Ten patients (the IDM group) received 50 mg of IDM every 8 h after operation up to postoperative day (POD) 4 while the other ten patients (the control group) received neither IDM nor any other non-steroidal anti-inflammatory drug, postoperatively. Though the requirement for postoperative plasma transfusion was significantly greater in the IDM group, the albumin level on POD 1 was significantly lower in this group than in the control group. The postoperative changes of C-reactive protein, retinol binding protein, and pre-albumin between the two groups showed no difference. Moreover, the urinary 3-methylhistidine excretion, N-balance, and plasma aminogram on POD 4 also demonstrated no difference. We thus concluded that post-operative IDM administration after elective surgery has no additional anti-catabolic effect on the presence of TPN.

Blood Proteins↗
PubMed1993

Effect of platelet on protein degradation in rat skeletal muscle.

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.

Animals↗