Suppression of induction of experimental immune mediated blepharoconjunctivitis by tolerogenic conjugates of the antigen and monomethoxypolyethylene glycol

AIM: Covalent conjugates consisting of diverse antigens coupled to optimal numbers of monomethoxypolyethylene glycol (mPEG) molecules have been shown to suppress antigen specific antibody formation. In this study, the possibility was examined that the same conjugates might prevent experimental immune mediated blepharoconjunctivitis (EC, formerly EAC) which had been shown to be caused by CD4(+) T cells-that is, to cell mediated immunity. METHODS: 6-8 week old male Lewis rats were used. The test groups of rats received two intravenous injections, each of 300 microg, of a conjugate of ovalbumin mPEG (OVA(mPEG)(11)) in phosphate buffered saline (PBS), 14 and 28 days before the single immunisation with OVA in complete Freund's adjuvant. The rats were challenged 3 weeks later by eye drops containing OVA; 24 hours later they were sacrificed, and their eyes, blood, and lymph nodes were harvested for histological examination and determination of anti-OVA antibody titres and levels of cellular immunity. Two control groups received PBS or OVA in PBS before immunisation. Furthermore, the possibility that OVA(mPEG)(11) may have induced OVA specific suppressor cells was tested by establishing the effects of the co-transfer of splenocytes from OVA(mPEG)(11) treated rats with OVA primed lymph node cells on the manifestations of EC. RESULTS: Either PBS or OVA pretreated rats, which had not received OVA(mPEG)(11), developed high levels of antibodies and cell mediated immune responses to OVA, and application of eye drops led to blepharoconjunctivitis with massive cellular infiltration. In contrast, pretreatment with OVA(mPEG)(11) prevented cellular infiltration into the lids and conjunctivas, as well as the formation of detectable humoral and cellular immunity against OVA. Co-transfer of splenocytes from OVA(mPEG)(11) treated rats with OVA primed lymph node cells suppressed the cellular infiltration on application of OVA on the conjunctiva. CONCLUSIONS: These data indicate that intravenous injection of OVA(mPEG)(11) conjugates suppressed both humoral and cellular immunity by the effects of antigen specific suppressor cells, thus leading to the inhibition of development of EC.     

Effect of dose intensity of methotrexate, doxorubicin, and ifosfamide on the prognosis of patients with osteosarcoma

Background. The prognosis of patients with osteosarcoma has improved due to the introduction of systemic chemotherapy. The current study tried to identify the effect of each anti-tumor drug on the prognosis of patients with osteosarcoma. Methods. The records of 29 patients with osteosarcoma who received systemic chemotherapy were retrospectively analyzed. All tumors were classified as stage IIB (Enneking's surgical stage) and were located around the knee joint or more distal areas. The histologic response to preoperative chemotherapy was determined in 20 patients: 9 patients had grade 1, 4 grade 2, 5 grade 3, and 2 grade 4. The mean follow-up period was 102 months. Results. The 5-year overall survival and relapse-free survival (RFS) in the 29 patients was 47.7% and 41.4%, respectively. The 5-year RFS for the 7 good responders (grade 3 and 4) was 85.7%, and that for the 13 poor responders (grade 1 and 2) was 23.1% (P = 0.008). The mean preoperative dose intensity (DI) of methotrexate (MTX) for good responders was significantly higher than that for poor responders (P = 0.028). In 23 patients who received MTX and doxorubicin (ADR) but not ifosfamide (IFOS), the DI of MTX significantly influenced the RFS (P = 0.0128). In the 13 poor responders, 6 of whom received IFOS, the DI of IFOS and ADR significantly influenced RFS (P = 0.0112, 0.0395). Conclusion. The preoperative DI of MTX was related to the histologic response rate. The DI of MTX was significartly associated with the patients' RFS. In poor responders, the DI of IFOS and ADR influenced the patients' RFS. Received: November 17, 1997 / Accepted: July 9, 1998     

Two cases of small cell lung cancer presenting an unusual pattern of progression mimicking pleural mesothelioma

We describe 2 cases in which small cell lung cancer presented an unusual pattern of progression that mimicked malignant pleural mesothelioma on diagnostic imaging. The patients were a 74-year-old man and a 69-year-old woman, both of whose chest roentgenograms and CT scans showed irregular right pleural thickening with effusion. Small cell lung cancer had been diagnosed by routine examination in the former patient, but the latter had been given a clinical diagnosis of pleural mesothelioma until postmortem examination, which showed small cell lung cancer. The right lung of each patient was found to be fused to the thorax by a thick layer of tumor cell involvement on postmortem examination.     

Stimulatory Effect of Interleukin-1α on Proliferation through a Ca2+/Calmodulindependent Pathway of a Human Thyroid Carcinoma Cell Line, NIM 1

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1α (IL-1α) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1α. Incubation of NIM 1 cells with IL-1α for 48 h increased the incorporation of ³H-thymidine (³H-TdR). The stimulatory effect of IL-1α was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1α evoked an influx of ⁴⁵Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01–1 ng/ml). These stimulatory effects of IL-1α on both ³H-TdR incorporation and ⁴⁵Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca²⁺ channels, in a concentration-dependent manner (10–1000 nM). The stimulatory effect of IL-1α on ³H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 m M Ca²⁺, inhibition of ³H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1α stimulates cell proliferation through a Ca²⁺/calmodulin-dependent pathway in NIM 1 cells.     

Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-Itax gene

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of thelyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.The abbreviations used are ATL, adult T-cell leukemia; HTLV-I, human T-cell leukemia virus type I; IL-2, interleukin 2; IL-2R, interleukin 2 receptor; IL-6, interleukin 6; LTR, long terminal repeat.     

FAMILIAL OXALOSIS REPORT OF THREE CASES AND REVIEW OF THE LITERATURE

An unusual disorder of familial oxalosis In three siblings is described. Autopsies were carried out in Case 1 and Case 2. The findings were characterized by the deposition of calcium oxalate crystals in the kidneys and various extrarenal organs. Hyperoxaluria, a pathognomonic sign in this disorder, and roentgenological nephrocalclnosis were demonstrated In living Case 3. Renal biopsy revealed minute intratubular deposition of calcium oxalate crystal. Result of electron microscopical investigation appeared to be normal. Chromosomal analysis of the family revealed no abnormality. Besides these three patients, one sister showed a slight elevation of urinary oxalate excretion. The mother, maternal uncle and aunt have suffered from microhematuria or urolithiasis, although urinary oxalate excretion is normal. Recent knowledges about the pathogenesis of primary oxalosis are reviewed and discussed.     

Once-daily theophylline reduces serum eosinophil cationic protein and eosinophil levels in induced sputum of asthmatics

BACKGROUND: Because eosinophilic airway inflammation is a characteristic feature of bronchial asthma, the treatment of airway inflammation is important in the management of asthma. Theophylline has been reported to reduce airway inflammation, in addition to its well-known bronchodilating effect. OBJECTIVE: In order to evaluate the effects of theophylline on airway inflammation, we investigated 48 subjects with mild and moderate asthma. METHODS: The patients were randomly divided into two groups, with or without theophylline treatment (control n = 24; theophylline, n = 24). We examined the level of serum eosinophil cationic protein (ECP), induced sputum samples, and peak expiratory flow (PEF) and obtained spirograms before and after 4 weeks of treatment with once-daily theophylline (200-600 mg/day) of subjects with mild or moderate asthma. RESULTS: Theophylline significantly increased morning and evening PEF and significantly decreased the diurnal variation of PEF. After treatment with theophylline, both serum ECP and the percentage of eosinophils in induced sputum were significantly decreased. In contrast, peripheral blood eosinophil count was unchanged after treatment with theophylline. Conclusions: These findings suggest that theophylline reduces airway inflammation and the severity of asthma, presumably via suppression of both eosinophil activity and subsequent eosinophil infiltration of the airways.     

Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a laryngeal tumor

Intraoral localization of neuroendocrine carcinoma, usually called Merkel cell carcinoma, is extremely rare. A case of neuroendocrine carcinoma that was a counterpart of laryngeal neuroendocrine carcinoma but was not a Merkel cell carcinoma, occurring at the mandibular gingiva in a 69-year-old Japanese man, is described. The tumor formed a cauliflower-like mass, measuring 20 × 20 mm, with a small area of necrosis. A computed tomography image showed metastasis in the right submandibular lymph node. Histopathologically, the tumor was composed of immature, small round cells that formed anastomosing trabecular nests. Few mitotic and no necrotic features were observed in the nests. Immunohistochemical studies showed positive staining for chromogranin, synaptophysin and neuron-specific enolase in the tumor nests. We diagnosed it as an atypical carcinoid (neuroendocrine carcinoma), a counterpart to the same type of tumor occurring in the larynx. The present case is an extremely rare case of neuroendocrine carcinoma without the feature of Merkel cell carcinoma arising from the gingiva.