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Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

At least 397 records · Page 22Linked to original sources

[The efficacy of intra-arterial infusion chemotherapy in patients with metastatic liver tumors].

The efficacy of intra-arterial infusion chemotherapy for the treatment of liver metastasis was investigated in 28 colorectal cancer patients, 3 gastric cancer patients and 5 breast cancer patients between April 1986 and May 1991. 1. The long-term intra-arterial infusion chemotherapy was a simple and safe method in cancer patients. 2. We examined the serial serum CEA level in cancer patients and found that the serial change in CEA level correlated well with response to chemotherapy. The efficacy of this treatment was approximately 60% in colorectal cancer, 30% in gastric cancer, 80% in breast cancer. Intra-arterial infusion chemotherapy may be an effective treatment for the patients with liver metastasis from colorectal cancers and breast cancers. 3. In 8 colorectal cancer patients, the serum CEA level decrease to half of the pretreatment level. However, in all cases it increased significantly within 6 months postoperatively. Almost the same trend was observed in two cases of breast cancer. Our results suggest that we should give careful consideration to the resistance to anti-cancer drugs and develop a new protocol in order to obtain further satisfactory results.

Administration, Oral↗

Effect of transcatheter arterial embolization on the boundary architecture of hepatocellular carcinoma.

Daughter nodules and intrahepatic metastases are resistant to conventional transcatheter arterial embolization therapy. To clarify the mechanism of this resistance, the boundaries of hepatocellular carcinomas and their relationship to the blood supply were studied. The boundaries of the hepatocellular carcinomas studied were classified as one of five types: encapsulated, granulation, stromal, replacing, or sinusoidal. The granulation and stromal types had a capsule-like structure, but lacked the hyalinization which is the hallmark of a true tumor capsule. The granulation and stromal types could also be differentiated from the encapsulated type because of their different blood supplies and the differing effects of transcatheter arterial embolization. When barium sulfate was infused into the portal vein, it did not enter into encapsulated tumors, but it entered granulation and stromal type tumors. Small nodules such as daughter nodules and intrahepatic metastases do not have capsules, and so have a blood supply that makes them resistant to conventional transcatheter arterial embolization therapy.

Autopsy↗

The role of CD8+ and CD4+ cells in islet allograft rejection.

The requirements of CD8+ and CD4+ cells for islet graft rejection in combinations with different histoincompatibilities were investigated by in vivo administration of anti-Lyt-2.2 (CD8) mAb, anti-L3T4 (CD4) mAb, or both to recipient mice. In B10.AQR----B10.A (H-2K-incompatible) and B10.A(5R)----B10.A (H-2K- and IA-incompatible) combinations, administration of either anti-Lyt-2.2 (CD8) or anti-L3T4 (CD4) mAb completely blocked islet graft rejection, indicating that neither CD8+ cells nor CD4+ cells alone were capable of mediating rejection, and that collaboration of CD8+ cells and CD4+ cells was necessary. On the other hand, in the BALB/c----B6 (H-2- and non-H-2-incompatible) combination, administration of anti-Lyt-2.2 (CD8) or anti-L3T4 (CD4) mAb resulted in rejection of most of the grafts, although survival was prolonged significantly, and administration of both anti-Lyt-2.2 (CD8) and anti-L3T4 (CD4) mAb together completely blocked rejection. These results suggested that either CD8+ or CD4+ cells were capable of mediating rejection, but that rejection was maximal in the presence of both T cell subsets. Immunohistochemical analyses showed marked depletion of CD8+ cells and CD4+ cells in grafted islets as well as spleens when anti-Lyt-2.2 (CD8) and anti-L3T4 (CD4) mAb, respectively, were injected.

Animals↗

Evidence that deoxyspergualin prevents sensitization and first-set cardiac xenograft rejection in rats by suppression of antibody formation.

This study provides evidence of antibodies playing an important role in hamster-to-rat cardiac xenograft rejection and discusses the use of 15-deoxyspergualin (DSG) to suppress this first-set rejection, as well as hyperacute rejection induced by sensitization. The effect of recipient splenectomy (Spx) as an adjuvant to DSG to control first set xenograft rejection was also examined. When hyperimmune serum was taken from control recipients at rejection time and injected i.v. into new recipients of cardiac xenografts, hyperacute graft rejection resulted. Survival depended on the amount of serum injected and ranged from 14.7 +/- 2.5 min with 3 ml of serum to 233.3 +/- 61.1 min with 0.5 ml. Experiments on first-set xenograft rejection revealed that a dose of 2.5 mg/kg/day DSG could prolong xenograft survival from 3.4 +/- 0.5 days in untreated controls to 9.5 +/- 2.6 days (P less than 0.01). A dose of 5 mg/kg/day DSG, though it increased graft survival to 16.4 +/- 5.9 days, proved to be toxic to the recipients. Spx alone prolonged xenograft survival to 5.2 +/- 0.4 days, and, when combined with 2.5 mg/kg/day DSG administration, prolonged graft survival to 22.1 +/- 5.5 days (P less than 0.01 vs. DSG alone). The appearance of cytotoxic antibodies was delayed, and titers decreased from 1:256 in untreated controls to 1:16-1:64 both in the group that underwent Spx only and in the group that received 2.5 mg/kg/day DSG. Combined treatment suppressed antibody response for more than two weeks. Experiments on hyperacute rejection induced by sensitization revealed that 1 ml of hamster whole blood transfused into prospective heart recipients 1 week before grafting resulted in graft loss in 18.2 +/- 6.1 min. Pretransplant transfusion and concomitant daily administration of 5 mg/kg/day DSG until one day after grafting not only prevented hyperacute rejection but prolonged graft survival to 7.0 +/- 0.7 days. This survival was significantly longer than with DSG alone (4.2 +/- 0.8 days, P less than 0.01). We concluded that the marked suppression of antibody formation by DSG plays a major role in preventing first-set xenograft rejection and hyperacute rejection induced by sensitization.

Animals↗

Regenerating nodules in hepatic cirrhosis: MR findings with pathologic correlation.

To establish clearly the pathologic basis for small low-intensity nodules seen on MR images of the cirrhotic liver, we obtained MR images in 26 patients with cirrhosis in whom partial hepatectomy for hepatoma (15 patients), laparoscopy for cirrhosis (10 patients), or autopsy (one patient) was subsequently performed. Small low-intensity nodules were seen on gradient-echo images with short TEs (10-13 msec) in 13 of the 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition. We conclude that small low-intensity nodules observed on MR images are caused by iron deposits in regenerating nodules, and that gradient-echo images with short and prolonged TEs are useful to confirm the presence of iron deposits in regenerating nodules.

Adult↗

[The clinical significance of PIVKA-II determination in patients with hepatocellular carcinoma: a comparative study with alpha-fetoprotein].

The changes in the plasma level of PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) following the treatment or progress of the disease was studied in 60 patients with hepatocellular carcinoma. The positivity rate determined by the changes in PIVKA-II was 58.4 percent (35/60 cases) and was about the same as those reported so far, all of which were obtained by a single determination of PIVKA-II. Plasma PIVKA-II was elevated in 61.9 percent (13/21 cases) of alpha-fetoprotein negative patients and it was almost identical with the overall positivity rate. In parallel with serum alpha-fetoprotein, the plasma level of PIVKA-II was decreased after the surgery or transcatheter arterial embolization and was increased when the recurrence or progress of the disease was observed. Furthermore, the nonspecific elevation of PIVKA-II due to the associated liver cirrhosis or chronic hepatitis was infrequent compared with that of alpha-fetoprotein. In 18 cases positive with both PIVKA-II and alpha-fetoprotein, a close correlation (R = 0.91) was observed between the changes of these markers during the progress or treatment of the disease. Thus, it was suggested that determination of PIVKA-II in blood might be useful not only in the diagnosis but in monitoring the progress or the effectiveness of treatments in hepatocellular carcinoma.

Adult↗

Successful islet isolation from preserved rat pancreas following pancreatic ductal collagenase at the time of harvesting.

In an attempt to develop an improved method for preserving the pancreas prior to islet isolation, the effects of warm and cold ischemia were examined on rat pancreases, from which reproducible high yields of islets can be obtained when fresh. Both warm and cold preservation rapidly decreased islet yield. Use of Hanks' or modified Sacks' solution also led to marked decrease in islet yield. After 6 hrs of preservation, the islet yield was 1/5-1/10 of those of fresh pancreases (374 +/- 74, n = 14), and no islets were obtained after 24 hrs of preservation regardless of the preservation solution. Monitoring of ductal pressure during forced injection of Hanks' solution in 6 hrs-preserved pancreas with HBSS showed a significantly earlier and lower peak of pressure than those of fresh pancreases. On the other hand, simple hypothermic preservation after pancreatic ductal distention with collagenase Hanks' solution at the time of harvesting resulted in a significantly higher islet yield up to 6 hours (171 +/- 58, n = 14, P less than 0.01), as compared with conventional methods. The viability of the islets isolated by this method was confirmed by the ability to restore normoglycemia of STZ-induced diabetic B6 mice on transplantation of 400 islets in the renal subcapsular space. These findings indicated that loss of the integrity of the ductal system against forced collagenase injection during cold preservation led to poor distention and digestion of the pancreas, ductal collagenase injection at the time of pancreas harvesting followed by simple preservation is recommended to obtain viable islets from the preserved pancreas.

Animals↗

Roles of CD4+ and CD8+ cells in islet allo- and xeno-graft rejection.

We investigated the requirement for and the roles of CD8+ cells and CD4+ cells for islet graft rejection in allogeneic and xenogeneic combinations by in vivo administration of anti-Lyt2 monoclonal antibody (mAb), anti-L3T4 mAb or both to the recipient mice. In BALB/c to B6 (H-2 and non-H-2 incompatible combination), administration of anti-Lyt-2.2(CD8) or anti-L3T4(CD4) mAb resulted in rejection of most of the grafts, although their survival was prolonged significantly. Administration of both mAbs together completely blocked rejection and all allografts survived over 100 days with mAb administration. In B10.A(5R) to B10.A (H-2K and IA incompatible combination) or B10.AQR to B10.A (H-2K incompatible combination), administration of either mAb alone induced indefinite allograft survival. In bm12 to B6 (IA incompatible combination), allografts were not rejected even in nontreated recipients. In rat-to-mouse combinations, administration of anti-L3T4 mAb produced marked prolongation of graft survival and 3 out of 8 survived over 100 days. Administration of both mAbs also led to prolongation of graft survival which was similar to or better than that of anti-L3T4 mAb alone. The present results indicated that CD4+ and CD8+ cells participate in all types of islet graft rejection studied here and that the absolute requirements of CD4+ or CD8+ T cell subsets for islet rejection depend on genetic as well as species disparity.

Animals↗

Treatment of hepatocellular carcinoma by segmental hepatic artery injection of adriamycin-in-oil emulsion with overflow to segmental portal veins.

Hepatocellular carcinoma was treated with slow injection of an emulsion containing 40 to 60 mg of adriamycin and 3.5 to 12 ml of Lipiodol into the portal vein via a segmental hepatic artery. During and after the injection, the portal branches of the segment were demonstrated. Six patients with resectable hepatocellular carcinoma received this treatment, which in 3 of them was followed by embolization with Gelfoam of the segmental artery. In these 3, all main tumors and daughter nodules became completely necrotic, but some infarction developed in the non-tumorous area. Those without Gelfoam had complete necrosis of all daughter nodules, but incomplete response of the main tumor. This combined treatment may be recommended for patients with localized lesions which are nonresectable due to cirrhosis, or for other reasons.

Aged↗