Selective intraarterial infusion of the ethylcellulose microcapsules of mitomycin C (MMC-mc) exerts its potential therapeutic effects through both infarction and prolonged local, drug activity, i.e., chemoembolization. Twenty patients with intractable primary, recurrent or metastatic carcinoma were treated with single or fractionated infusion of MMC-mc via percutaneous arterial catheterization. The target sites were the kidney, liver, prostate, urinary bladder, uterus, sigmoid colon, Douglas' pouch and bone. Fourteen patients had over 30% reduction in measurable maximum tumor diameter, 5 had 10 to 30% reduction and 1 showed less than 10% reduction, but concurrent 2 bone lesions had no reduction. Improvement of symptoms and signs such as pain, massive hemorrhage, dysuria, anorexia and hydronephrosis was observed at an early stage of the treatment in all patients. Eight patients with highly invasive carcinoma of the kidney, urinary bladder and cervix were initially treated with MMC-mc followed by successful radical operation. Systemic toxicity was mild and all patients tolerated the treatment. Although the follow-up periods are less than 21 months, 12 patients are alive with or without tumor and 11 of them are doing well. The present results indicate that chemoembolization with MMC-mc is effective as a preoperative or palliative measure in the treatment of invasive carcinoma of various organs.

Adult↗

PubMed1981

Arterial chemoembolization with microencapsulated anticancer drug. An approach to selective cancer chemotherapy with sustained effects.

Selective intra-arterial infusion of ethylcellulose microcapsules containing mitomycin exerts its therapeutic effects through infarction and sustained drug action--ie, chemoembolization. Sixty primary or secondary carcinomas in the kidney, liver, urinary bladder, prostate, cervix, vagina, sigmoid colon, Douglas' pouch, and bone were treated with single or repeated chemoembolizations using microcapsules delivered through percutaneous catheterization as a preoperative or palliative measure. Substantial tumor reduction of greater than 30% in measurable maximum diameter was found in 65% of the tumors, pain relief occurred in 80% and hemostasis in 100%. Preoperative chemoembolization remarkably facilitated radical surgery in 18 (82%) of 22 patients. The summed response rate was 77%. Systemic toxic effects were mild, and all patients tolerated the treatment. Though the follow-up periods are less than two years, 37 patients are alive with or without tumor.

Clinical Trials as Topic↗

PubMed1981

Comparison of dipeptidyl peptidase IV prepared from pig liver and kidney.

Dipeptidyl peptidase IV (dipeptidylpeptide hydrolase, EC 3.4.14.-) has been purified from the microsomal fraction of pig liver, using an immunoaffinity chromatography, and its properties compared with those of the enzyme purified from pig kidney. The amino acid compositions of both enzymes were similar. The same kinds of carbohydrates were found in both enzymes, but there were differences in the molar concentrations of individual sugars. The liver enzyme had greater concentrations of mannose, fucose and sialic acid than the kidney enzyme, while the concentrations of galactose and glucosamine were greater in the kidney enzyme. The carbohydrates accounted for approx. 18.3 and 22.7% of the weight of the kidney and liver enzymes, respectively. The pH optima, molecular weights, substrate specificities and Km values of the two enzymes and the effects of diisopropylfluorophosphate on their activities were nearly identical. The liver enzyme was heat- and pH-sensitive, but not attacked by proteinases.

Amino Acids↗

PubMed1981

Phosphoprotein phosphatase activity of bovine intestinal alkaline phosphatase.

The phosphoprotein phosphatase activity of a commercial preparation of bovine intestinal alkaline phosphatase (EC 3.1.3.1) was examined using phosvitin and dentine phosphoprotein as substrates. Over 90% and 70% of the phosphorus from dentine phosphoprotein and phosvitin were hydrolyzed in 2 h. The optimum pH of the enzyme for the dephosphorylation of phosvitin and dentine phosphoprotein was nearly 6. No protein phosphatase activity was observed when the alkaline phosphatases from bovine liver and pulp were investigated.

Alkaline Phosphatase↗

PubMed1981

Purification and properties of dipeptidyl peptidase IV from Streptococcus mitis ATCC 9811.

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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases↗

PubMed1981

Effect of antithymocyte globulin on histocompatibility antigen recognition in man.

Nonmajor histocompatibility complex (non-MHC) antigens are important targets of graft rejection and graft-versus-host disease in clinical transplantation. Little is known regarding immunity to non-MHC antigens. To study this problem we evaluated the effect of antihuman thymocyte globulin (ATG) on reactivity in autologous and allogeneic mixed lymphocyte cultures and activity in a model of immunity to non-MHC antigens, the response to trinitrophenyl (TNP)-modified autologous cells. Primary proliferative responses to autologous B lymphocytes, allogeneic cells, and TNP-modified autologous cells were all inhibited by ATG treatment. Secondary proliferative responses and cytotoxicity to TNP-modified autologous cells were also inhibited as was cross-reactive cytotoxicity to TNP-modified allogeneic cells. These data indicate that both MHC-restricted and MHC-nonrestricted immune responses to modified self-antigens and possibly to non-MHC antigens are sensitive to ATG treatment. ATG may be useful in clinical situations where the objective of immunosuppression is to inhibit immunity to non-MHC antigens such as after HLA-matched kidney grafting or bone marrow transplantation.

Antilymphocyte Serum↗

PubMed1981

Evaluation of antithymocyte globulin for human bone marrow transplantation. III. Effect of antithymocyte globulin treatment on t cell precursors.

The effect of antithymocyte globulin (ATG) treatment on T cell precursors was investigated in an in vitro model of E rosette induction by thymic factors. Approximately 8% of bone marrow mononuclear cells can be induced to form E rosettes following incubation with thymosin or with conditioned medium from cultured thymic epithelium (CM-CTE). Treatment of bone marrow mononuclear cells with ATG alone markedly reduced but did not eliminate precursors of E rosette-forming cells (E-RFCs), whereas treatment with ATG and complement completely inhibited these bone marrow E-RFC precursors. E-RFCs already present in peripheral blood and bone marrow were completely inhibited by treatment with ATG alone. E-RFCs induced by treatment of bone marrow cells with thymosin or CM-CTE were also completely inhibited by ATG alone. These data indicate that bone marrow precursors of E-RFCs are less sensitive to ATG inhibition than are peripheral blood and bone marrow E-RFCs. When bone marrow precursor T cells are induced to become E-RFCs by the treatment with thymic factors, they acquire comparable sensitivity to ATG. A similar disparity in sensitivity to ATG treatment was observed when ATGs absorbed with human fetal liver cells or granulocytes were studied. These data suggest that ATG treatment of bone marrow cells may have different effects on mature and precursor T cells. It is important to consider these factors in attempts to use ATG treatment in clinical bone marrow transplantation trials.

Antilymphocyte Serum↗

PubMed1981

Impaired cell-mediated immunity in lipoid nephrosis.

Cell-mediated immunity (CMI) was evaluated in 26 patients with lipoid nephrosis (LN), 50 patients suffering from chronic diffuse proliferative glomerulonephritis (CGN) without renal sufficiency and 24 healthy controls. The following parameters were measured: delayed hypersensitivity skin test responses to purified protein derivative (PPD) and candida, circulating lymphocytes. T lymphocytes and T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) or IgM (Tmu cells). Patients with LN in relapse had less mean induration of skin reactivity and a smaller proportion reacting to both antigens as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in patients with LN in remission and CGN were similar to those of the control subjects. It was also found that the LN patients in relapse had a significant T lymphocytopenia as well as a significant decrease in absolute numbers of Tmu and T gamma cells, whereas the patients with LN in remission and CGN did not differ significantly from the control population. Thus, the majority of patients with LN in relapse demonstrated an impaired response in a CMI assay system. The disturbed CMI may be secondary to hypoproteinemia and other nutritional factors induced by the nephrotic syndrome.

Adolescent↗

PubMed1981

Cell-mediated immunity in idiopathic membranous nephropathy.

Cell-mediated immunity (CMI) was evaluated in 11 patients with idiopathic membranous nephropathy (MN), 50 patients suffering from chronic proliferative glomerulonephritis (CGN) without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative (PPD), circulating lymphocytes, lymphocyte cell-surface markers (En and EAC rosettes) and functional markers (mitogenic responses to Con A and PHA). The MN patients with nephrotic syndrome (NS) had less mean induration of skin reactivity and a smaller proportion reacting to the PPD antigen as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in MN patients in remission and CGN were similar to those of the control subjects. During the nephrotic stage of MN the proportion of T lymphocytes decreased with simultaneous increase of the proportion of B lymphocytes. It was also found that the MN patients with NS showed impaired lymphocyte reactivity with lower Con A and PHA responses compared to the normal controls. Conversely, the mean mitogenic responses to the antigens in patients with MN in remission and CGN were similar to those of the control subjects. Thus, the majority of MN patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Adult↗