picibanil and Chronic-Disease

A 52-year-old woman with thoracic esophageal carcinoma was admitted to our hospital. Standard radical esophagectomy was carried out via a right posterolateral thoracotomy and laparotomy. A drainage tube was removed from the right side of the chest on the 9th postoperative day. Three days later a chest roentgenogram showed massive left pleural effusion, and a tube was inserted into the left pleural cavity. The volume of the effusion was 900 ml/day and chylothorax was diagnosed. Conservative therapy was applied for 30 days, but chyle leakage persisted. Intra-pleural infusion of OK-432, a Su-strain of Streptococcus pyogenes, and doxycycline hydrochloride was carried out to seal the leakage point. The effusion stopped immediately after the procedure. There were no major side effects. This procedure should be considered the treatment of choice for patients with persistent chylothorax not responding to initial conservative management.

Topics: Chronic Disease; Chylothorax; Esophageal Neoplasms; Esophagectomy; Female; Humans; Middle Aged; Picibanil; Pleurodesis

We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.

Topics: Cells, Cultured; Chronic Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Hepatitis B; Hepatitis C; Humans; Immunologic Factors; Interferon-gamma; Interleukin-1; Interleukin-6; Leukocytes, Mononuclear; Picibanil; Streptococcus

Topics: Adjuvants, Immunologic; Adult; Aged; Biological Products; Chronic Disease; Drug Evaluation; Drug Therapy, Combination; Female; Hepatitis C; Hepatitis, Viral, Human; Humans; Interferon Type I; Liver; Male; Middle Aged; Picibanil; Pilot Projects; Recombinant Proteins

Host-mediated antiviral effect of 2 biological response modifiers (BRM), OK-432, and PS-K, against murine cytomegalovirus (MCMV) was evaluated in chronically or latently infected mice. In the early stage of chronic MCMV infection, the BRM-induced resistance was evidenced by decrease in infectious viruses replicated in the salivary glands and by augmented cytotoxic activity of the spleen cells against YAC-1 cells and MCMV-infected mouse embryonic fibroblasts (MEF). In the late stage of chronic MCMV infection, the BRM treatment did not eliminate MCMV from the mice, but did prevent exacerbation of MCMV infection in the salivary glands induced by administration of cyclophosphamide (CY). In mice latently infected by MCMV, BRM treatment suppressed CY-induced reactivation of MCMV in the salivary glands. It was suggested that the antiviral effect of BRM against MCMV in chronically or latently infected mice was based on activation of natural killer (NK) cells and cytotoxic T lymphocytes (CTL).

Topics: Animals; Antibodies, Viral; Antiviral Agents; Biological Products; Cell Line; Cells, Cultured; Chronic Disease; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Cytotoxicity, Immunologic; Female; Immunosuppression Therapy; Interferons; Killer Cells, Natural; Mice; Mice, Inbred DBA; Mice, Inbred ICR; Picibanil; Proteoglycans; Salivary Glands; T-Lymphocytes, Cytotoxic; Virus Replication

Natural killer (NK) activity in the peripheral blood of patients with chronic liver disease was measured using 51Cr labeled K562 cells as target cells. NK activity was elevated but not significantly in patients with chronic hepatitis compared with healthy controls and significantly lower in the patients with hepatocellular carcinoma. The activity decreased in the order of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the level of NK activity in patients with chronic hepatitis did not correlate with the level of alanine aminotransferase (ALT), it tended to be elevated in association with elevation of ALT in patients treated with OK432, interferon-beta, glycyrrhizin or adenine arabinoside. In chronic liver disease, phytohemagglutinin (PHA) skin test showed a positive correlation with NK activity. In all patients who were treated with the immunopotentiator, OK432, and whose HBeAg became negative, NK activity was elevated during the treatment. These results suggest that the NK activity in peripheral blood may be related to hepatocytic injury even if this is not the effector mechanism of the injury.

Topics: Adult; Carcinoma, Hepatocellular; Chronic Disease; Cytotoxicity, Immunologic; Female; Glycyrrhetinic Acid; Glycyrrhizic Acid; Hepatitis B; Humans; Interferon Type I; Killer Cells, Natural; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Picibanil; Radioimmunoassay; Skin Tests; Vidarabine

We studied the effect of intraperitoneal injection of OK-432 on the growth of original tumor mass in patients with malignant ascites and a possible mechanism of reduction of tumor volume. Sixteen patients with valuable original tumor mass and a large amount of ascites caused by gastro-intestinal cancer were studied. Tumor cells were separated from ascitic fluids and cultured in vitro before the study. Lymphocytes were collected from the fluids at varying intervals after intraperitoneal injection of OK-432 and cultured 24 hours in vitro. Effect of the culture supernatant on ascites-derived autologous tumor cell growth was examined in vitro using microplate assay. The results were as follows. 1) Reduction of tumor mass more than four weeks was found in 4 of 16 cases. 2) Before OK-432 injection, the culture supernatant from ascites-derived lymphocytes did not inhibit autotumor cell growth in vitro. But, the supernatant from lymphocytes which were collected from the ascites after OK-432 injection markedly inhibited tumor growth in all of 4 tumor mass reduction cases. In 12 non-reduction cases the supernatant slightly inhibited tumor growth only in 2 cases. 3) A similar growth inhibitory factor was detected in the mixed culture-supernatant of peripheral blood lymphocytes and OK-432 in vitro. 4) Preliminary studies indicated that the tumor growth inhibitory factor might be different from tumor necrosis factor and interferons. These results indicate that ascites-derived lymphocytes-producing factor may play an important role in reduction of tumor mass volume in patients with cancerous ascites.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Chronic Disease; Female; Gastrointestinal Neoplasms; Humans; Injections, Intraperitoneal; Male; Middle Aged; Peritonitis; Picibanil

Forty-two patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis were treated by intramuscular injections with OK-432, an immunopotentiator possessing interferon-inducing activity. They were monitored with serial measurements of virological parameters to evaluate therapeutic effectiveness, and compared with a group of seventy-five untreated patients (natural course group). In the group receiving OK-432 therapy, twenty-seven patients (64.3% of the forty-two patients) became negative for HBeAg in an average observation period of 20.1 months. Of these, fourteen patients (33.3% of the forty-two patients) underwent seroconversion from HBeAg to anti-HBe antibody (anti-HBe). In the natural course group, twenty-three patients (30.7% of the seventy-five patients) lost HBeAg reactivity in a mean follow-up period of 32.3 months, and thirteen patients (17.3% of the seventy-five patients) became seroconverted. Thus, the drug group showed significantly higher percentages of patients with disappearance of HBeAg and seroconversion, notwithstanding the shorter duration of the follow-up. Young males and females, females generally, or patients with high serum GPT levels were more likely to respond to the therapy. The serum GPT level tended to stabilize more in patients receiving OK-432.

Topics: Adult; Alanine Transaminase; Biological Products; Chronic Disease; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Antigens; Hepatitis B e Antigens; Humans; Male; Picibanil

Topics: Adjuvants, Immunologic; Catechin; Chronic Disease; Hepatitis B; Humans; Interleukin-1; Picibanil; T-Lymphocytes

Topics: Adjuvants, Immunologic; Biological Products; Chronic Disease; Female; Hepatitis B; Hepatitis B Antigens; Hepatitis B e Antigens; Humans; Male; Picibanil