Immunocytochemical detection of bone marrow-invasive neuroblastoma cells

Abstract: We evaluated the utility of an immunocytochemical technique employing the commercially available anti-CD56 monoclonal antibody, NKH 1. The utility and sensitivity of this technique in the detection of invasive neuroblastoma (NB) cells in the bone marrow were compared with those of Wright-Giemsa staining. The correlation coefficient for the percent NB cells detected using Wright-Giemsa staining with the percent NKH 1 immunoreactive cells was 0.78. In the analysis of specificity, this monoclonal antibody showed slight cross-reactivity with normal bone marrow cells, including macrophages, lymphocytes and osteoblasts. In the evaluation of the sensitivity of the NKH 1 immunocytochemical technique, SK-N-DZ and SK-N-SH NB cell lines were added to morphologically normal bone marrow mononuclear cells from patients without NB to the final NB cell line at concentrations of 2%, 1% and 0.1%. NB cells at the final concentration of 0.1 % could be detected by the immunocytochemical technique. We conclude that the NKH 1 immunocytochemical staining technique is useful in the detection of metastatic NB cells in bone marrow.     

Large volume intraperitoneal chemotherapy as treatment for the peritoneal carcinomatosis from gastric cancer]

Gastric cancer sometimes spread to peritoneal surfaces in the absence of lymphatic or hematogenous metastases. For the treatment of peritoneal carcinomatosis, we applied large volume intraperitoneal chemotherapy (L.V.I.C.). In L.V.I.C., drugs were administered with large volume of saline through the reservoir buried in the subcutaneous tissue of the abdominal wall. We used mitomycin C (MMC), 5-fluorouracil (5-FU) and CDDP and examined the pharmacokinetics of these drugs when they were administered by this method to the patients of peritoneal carcinomatosis. A marked pharmacokinetic advantage was observed when 5-FU and CDDP were administered. AUC of these drugs were much larger than that of MMC. In vitro sensitivity test (SDI test) was useful for the selection of adequate drugs for each patient. On this method, drugs were distributed widely in the abdominal cavity and the patients could be taken this treatment repeatedly as out-patient. L.V.I.C. seems to fulfill the need for a safe, effective and acceptable delivery system of intraperitoneal chemotherapy.     

Simultaneous Expression of Type IX Collagen and an Inhibin-related Antigen in Proliferative Myoepithelial Cells with Pleomorphic Adenoma of Canine Mammary Glands

To identify an alcian blue-positive component expressed in the early stage of mammary mixed tumor and to pursue the possible involvement of a tumorigenic inducing factor, monoclonal antibodies to type IX collagen were generated and used to investigate the immnnohistochemical kinetics of type IX collagen expression by the myoepithelial cell-derived chondrocyte-Uke cells during the development of chondrometaplasia. We also examined the expression of inhibin-related antigen using antibodies to a synthetic peptide spanning amino acids 1–30 of the inhibin α chain. At the earliest stage of chondrometaplasia, where myoepithelial cells began to proliferate inside the basement membrane, the cells expressed type IX collagen together with an inhibin-related antigen which was immunoreactive with the anti-inhibin peptide antibodies. The expression of the inhibin-related antigen was also demonstrated in normal embryonic chondrocytes and myoblasts, but was much less strong in mature chondrocytes and myotubes, strongly suggesting that the inhibin-related antigen is involved in the development of chondrocytes and myoblasts from undifferentiated mesenchymal cells as well as proliferating myoepithelial cells as a chondro-progenitor cell in the mammary mixed tumor. The pathophysiological significance of type IX collagen expression as a possible cell marker of the progenitor cell in myoepithelial cell-related chondrometaplasia is also discussed.     

A case of idiopathic interstitial pneumonia with cytomegalovirus infection]

A 67-year-old female was admitted to our hospital because of fever, dry cough, and exertional dyspnea. The findings of chest X-ray, transbronchial lung biopsy, and bronchoalveolar lavage were compatible with the diagnosis of idiopathic interstitial pneumonia. Prednisolone was administered and she felt better for a while. However, she developed severe dyspnea, and marked diffuse infiltrative shadows were observed on chest X-ray after 3 months of steroid therapy. In spite of pulse therapy with methylprednisolone, she died of severe respiratory failure. Complement fixation test and IgG antibody enzyme immunoassay for cytomegalovirus were positive, but there was no change the titers between admission and death. IgM antibody was negative. The lung findings at autopsy compatible with usual interstitial pneumonia and diffuse alveolar damage, moreover, cytomegalovirus infection was observed. We consider that recurrent cytomegalovirus pneumonia had been present due to secondary immunodeficiency caused by administration of steroid hormones.     

Advances of BRM therapy of malignant brain tumors

The cooperative study on the beta-interferon (IFN) therapy for glioblastoma and malignant astrocytoma reported the response rate as 14.0%. Continuing study resulted the response rate of 24.0% to low grade astrocytoma and 20.0% to medulloblastoma. Totally, effectiveness of 19.2% to gliomas was confirmed in 120 evaluated cases. A randomized study was conducted on combination therapy with beta-interferon and chemoradiotherapy. The response rate of 41.2% (21/51) in the group treated with IFN, ACNU and Radiation was significantly higher than the rate of 19.6% (10/51) in the group treated with ACNU and radiation only. Application of IFN to a maintenance therapy is also on going. Adoptive immunotherapy has been developed as potential therapeutic method of malignant glioma. Lymphokine activated killer cells (LAK) and Tumor infiltrating lymphocytes (TIL) are put to clinical use. Clinical application of human monoclonal antibody (MAb) CLN-IgG was conducted to recurrent malignant glioma. 131I labeled MAb was administered intratumorously and the specific incorporation was confirmed by gamma-scintigraphy. Concomitant administration of interferon enhanced the efficacy of the therapy. This radio-immunotherapy holds future promise as a new therapeutic approach to gliomas.     

Anti-allergic action of glucocorticoids (II). Effect of glucocorticoids on cell mediated (type IV) allergic reactions

The effects of three glucocorticoids (steroids; hydrocortisone, prednisolone and dexamethasone) on cell mediated hypersensitivity (type IV) reactions in rats and mice were studied. All the steroids inhibited both the induction and the effector phases of type IV reaction induced by sheep red blood cells (SRBC) in mouse footpads. The local graft vs host reaction induced by lymphocytes from Brown Norway rats into the footpads of (Lewis x Brown Norway) F1 rats was also clearly inhibited by steroids. The inhibitory action of steroids on footpad reactions induced by SRBC was clearly prevented by pretreatment with non-corticoidal steroids (17 alpha-methyltestosterone, androstenedione and progesterone). The release of lymphokines, macrophage chemotactic factor (MCF) and skin reactive factor (SRF) was inhibited by each steroid at a high concentration. Moreover, steroids inhibited the activity of MCF in vitro and SRF in vivo.     

Effect of cigarette smoking and dietary factors on the amount of N-nitrosothiazolidine 4-carboxylic acid and N-nitroso-2-methyl-thiazolidine 4-carboxylic acid in human urine

The effects of cigarette smoking and dietary factors on urinary excretion of N-nitrosothiazolidine 4-carboxylic acid (NTCA; N-nitrosothioproline) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA; N-nitroso-2-methylthioproline) were studied in a male volunteer and in healthy Japanese subjects from the general population and Seventh-Day Adventists (SDA). Twenty-four-hour urine samples from the male volunteer were collected on 20 smoking days and 20 nonsmoking days during ingestion of a fixed diet, and the amounts of urinary N-nitrosamino acids were analysed by gas chromatography-thermal energy analysis. Cigarette smoking caused about two-fold (significant) increases in the amounts of NTCA and NMTCA in the volunteer. In the male subjects from the general population, not controlled for diet, the amounts of NTCA and NMTCA in 24-h urines of smokers were also significantly higher than those of the nonsmokers. The urinary excretions of NTCA and NMTCA in SDA were lower than those of nonsmokers in the general population. It was concluded that cigarette smoking is one of the important factors in determining the amounts of NTCA and NMTCA in human urine. Dietary factors also apparently influence the urinary levels of these N-nitrosamino acids. In addition, an apparent sex difference in the urinary excretion of NTCA and NMTCA (about two-fold higher in females) was observed in the general population but not in SDA. The N-nitrosoproline (NPRO) level was significantly higher in SDA than in nonsmokers in the general population.     

The diagnostic value of immunoglobulin G in the cerebrospinal fluid of brain tumor patients, particularly in malignant tumors

The diagnostic value of immunoglobulin G in cerebrospinal fluid (CSF-IgG) has been evaluated in patients with brain tumors. The (CSF-IgG) level in patients with malignant brain tumors was found to be significantly elevated when compared to the level in control patients without a disorder of the central nerve system. Especially significant was high level of CSF-IgG found in patients whose tumor had invaded into ventricles. The CSF-IgG level was found to decrease to a normal range by a total or subtotal resection of the tumor, but not by partial resection. On the other hand, CSF which contained large amount of IgG inhibited the lymphocyte proliferative response to phytomitogen. These results suggest that CSF-IgG seems to correlate with the tumor volume, and is important as a tumor marker in patients with a malignant brain tumor.