Makoto Ohnishi

Hodgkin's disease and Sjögren's syndrome

To the editor: It is well known that B-cell lymphoma is an occasional complication of Sjogren’s syndrome (SS) (13). Hyperimmune reaction has been assumed to play an important role in its lymphomagenesis. In contrast, there have been few reports on a causal association between Hodgkin’s disease (HD) and SS. Recently, Martin-Santos et al. reported a case of HD in a patient with primary S S and suggested that S S increases the risk of HD as well as non-Hodgkin’s lymphoma (NHL); however, the precise pathogenesis was unclear (4). In this paper we also describe a patient with SS who developed HD, and discuss the possible pathogenesis of these two disorders. The patient, a 69-year-old Japanese woman, was first admitted to our hospital because of left herniplegia in 1988. She also had a 4-yr history of keratoconjunctivitis sicca that required treatment with methylcellulose eye drops. Physical examination on admission revealed spastic paralysis of the left upper and lower extremities. Brain computed tomography showed a right putaminal hemorrhage. Abdominal sonography showed mild splenomegaly, but no nodular lesion was observed. Hematologic studies revealed a hemoglobin level of 12 g/dl, a leukocyte count of 2500/p1 and a platelet count of 8.7 x 104/pl. The total plasma protein level was 7.4g/dl, with a slight increase in the gammaglobulin fraction (23 %). Immunoglobulin concentrations were IgG, 1970 mg/ dl; IgA, 520 mg/dl; and IgM, 160 mg/dl. Antinuclear antibody (ANA) was positive at a dilution of 1:80. Serological tests were positive for rheumatoid factor (RF) and anti-SS-A, but negative for anti-SS-B antibody. Examination by an ophthalmologist showed diminished tear production (Shirmer tear test 3 mm for the right eye and 5 mm for the left eye) and punctate keratitis on rose bengal testing. Lip biopsy showed focal infiltratian of mononuclear cells and mild fibrosis, predominantly periductal in distribution (Fig. 1A). The patient was diagnosed as having SS. She remained &ell with symptomatic treatment until April 1992, when she noticed swelling of the right neck lymph node. Examination revealed hepatosplenomegaly with the spleen palpable 5 cm below the left costal margin. Abdominal computed tomography revealed a nodular lesion in the upper portion of the spleen. X-ray examination of the chest showed an enlarged right hilar lymph node and multiple nodular shadows in both lung fields. Laboratory examinations yielded the following results: total protein, 8.5 g/dl (gamma-globulin, 29%); IgG, 2700 mg/dl; IgA, 560 mg/dl; and IgM, 80 mg/dl. ANA and RF were negative. A biopsy specimen obtained from the right neck lymph node showed the presence of typical Reed-Sternberg (RS) cells with loss of the normal architecture of the node (Fig. 1B). The patient was diagnosed as having HD of mixed cellularity. Combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone resulted in considerable improvement of the splenomegaly and the chest radiograph abnormalities. Since Talal’s report, many studies have emphasized the correlation between SS and the development of NHL (1-3) Many theories have been proposed to account for this association, including exposure to radiation, previous cytotoxic chemotherapy, genetic predisposition, and intense antigenic stimulation (1-3). The fact that most of these lymphomas are derived from B lymphocytes may support the hypothesis that a chronic state of immunological hyperactivity is responsible for the malignant transformation (3). Although a few cases of patients with T-cell lymphoma and SS have recently been reported (5 , 6),fhe development of HD is rare. Since our patient did not have a history of either irradiation or immunosuppressive chemotherapy before the development of HD, a hyperimmune reaction of SS may have played a role in its pathogenesis. RS cells are pathognomonic of H D and are considered to be the neoplastic population in this disease. The cellular origin and nature of H D are still obscure; however, molecular genetic analysis had demonstrated clonal lymphocyte populations in many patients with H D (7-lo), supporting the concept that H D is a lymphocytic disorder. Meanwhile, recent studies have detected Epstein-Barr virus (EBV) DNA (10, 11) and mRNA (12) in RS cells, suggesting that EBV may be the transforming agent in some cases of HD. Interestingly, Miyasaka et al. reported that

Involvement of Annexins I an II in human liver cirrhosis and hepatocellular carcinoma

Annexin (AX) is the name of a new family of Ca2+-dependent membrane binding proteins of which 13 members have been reported to date. Among these, AXI and AXII have been reported to possess many biological functions in vitro. Their actual roles in vivo, however, are as yet unknown. There have been no reports previously demonstrating the direct involvement of AXI and AXII in chronic hepatitis (CH), liver cirrhosis (LC) or hepatocellular carcinoma (HCC). The involvement of AXI and AXII in the etiological processes of CH, LC and HCC was investigated by Western blot and/or immunohistochemistry using anti-AXI and AXII antibodies. AXI and AXII were rarely detected in CH liver tissues, while they were found to be expressed at high levels in LC and HCC. AXI and AXII were present in the hepatocytes of LC and HCC and their subcellular localization was mainly cytoplasmic. These results indicate that AXI and AXII may act together in the occurrence and development of LC and HCC.

Distribution and developmental changes of annexin V in rat pancreatic islets

Abstract We investigated the expression patterns and the dynamic changes of annexin V in the rat pancreatic islets during postnatal development by both Western blot analysis and immunohistochemistry using polyclonal anti-annexin V antibodies. Pancreatic islets were exclusively shown to express annexin V, while exocrine tissues were not. Pancreatic duct cells and capillary endothelial cells in the pancreas were also stained. Annexin V was present in both A and B cells in islets. Strong staining was detected on the cell membrane and in peri-membranous areas of islet cells. The expression level of annexin V in pancreatic islets gradually increased with postnatal development to remain constant after the 12th week of life. The present study suggested that annexin V may be concerned with the maturation of islet functions.

Increases in src-related protein tyrosine kinases in human liver cirrhosis and hepatocellular carcinoma

Abstract We examined the involvement of src-related tyrosine kinases (RTK) in various human liver diseases, such as chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular careinoma (HCC), by Western blot and immunohistochemical analysis using an anti-src-RTK polyclonal antibody (α-416). Our results showed that src-RTK were rarely found in the liver tissues from CH patients, while they were found at high amounts in those from LC and HCC patients. In addition, src-RTK were expressed more strongly in HCC than in LC. These results indicate that src-RTK may play important roles in the occurrence and development of LC and HCC.