Somatic cell gene therapy has made considerable progress last five years and has shown clear success in some clinical trials. In the field of nephrology, both the elucidation of pathophysiology of renal diseases and the development of gene transfer technique have become driving force for new therapy of incurable renal diseases, such as Alport syndrome and polycystic kidney disease. Gene therapy of renal cancer, although its application is limited to advanced cancer, is the front-runner of clinical application. Erythropoietin gene therapy has provided encouraging results for the treatment of anemia in uremic rats and recently progressed to the inducible one in response to hypoxia. Gene therapy for glomerulonephritis and renal fibrosis showed prominent impact on experimental models, although the safety must be confirmed for prolonged treatment. Transplant kidney is an ideal material for gene modification and induction of tolerance in the transplant kidney is an attractive challenge. Emerging techniques are becoming available such as stem cell technology and messenger RNA silencing strategies. We believe that the future of gene therapy research is exciting and promising and it holds an enormous potential for clinical application.
Objective Blood (1→3)-β-D-glucan (βG) measurement is widely used as an effective sero-diagnostic method for deep-seated mycosis. Antitumor βG (lentinan, schizophyllan) administration is known as one of the false-positive factors of blood βG measurement. To understand the influence of administered βG preparation to βG measurement in blood, we compared the interfering effect of βG administration in different βG measuring methods. Methods βG concentration in plasma was measured by three different methods. Materials βG concentration was measured in plasma of 18 samples of 7 cases with βG administration and 86 samples without βG administration. The period after last βG administration was three days to three years. Results In the cases for which βG was administered, blood βG level drastically increased using the method which employs alkaline pretreatment. Even in the cases for which βG was administered three years previously; βG value measured by alkaline pretreatment was significantly high. Thus, interference of βG administration in blood βG measurement continued for years after the last administration. Conclusion Disparity in βG values measured by different methods for βG administered cases is due to differences among sample pretreatment methods. Conformation of administered βG seemed to be transformed into a sensitive form to factor G by alkaline pretreatment. Especially in the case of the alkaline pretreatment method, βG administration disturbance was much stronger than for dilution-heating pretreatment. Therefore, in suspected cases, it is important to pay attention to βG administration during the previous few years.
A 69-year-old man was admitted with a large elastic mass in the upper abdomen. Computed tomography revealed a massive tumor in contact with the liver and gastrointestinal endoscopy revealed a gastric adenocarcinoma. He developed acute renal failure with massive proteinuria and died with a marked enlargement of the tumor. Autopsy revealed a tumor located in the lesser omentum. The tumor was considered to be a Gastrointestinal Stromal Tumor (GIST) because it was positive for c-kit. In addition, crescent formations and immune complexes in glomeruli were observed. We report the first case of GIST complicated by rapidly progressive glomerulonephritis and gastric carcinoma.
Diagnostic imaging of a 70-year-old woman revealed widespread lymph node swelling and pyloric stenosis due to alpha fetoprotein-producing gastric cancer. Second line chemotherapy of irinotecan and mitomycin C was administered after S-1 failure. After 6 courses of 2nd line chemotherapy, pyloric stenosis was improved, and lymph node swelling disappeared. This patient has been alive without disease for more than 3 years since 2nd line chemotherapy began and for more than 4 years since her first admittance to our hospital. Second line chemotherapy may have contributed to the favorable clinical outcome in this patient.
A 65-year-old was admitted to our hospital and was diagnosed as having squamous cell carcinoma originating in the right upper bronchus. He underwent both chemotherapy and radiation therapy, but these therapies were ineffective and thereafter the developed radiation pneumonitis and carcinomatous pleuritis. Finally, he died of bacterial pneumonia in the opposite normal lung of four months duration. From one month before his death, laboratory data indicated marked leukocytosis, and his granulocyte colony-stimulating factor (G-CSF) serum level was high. At autopsy, squamous cell carcinoma was found in the right hilus region of the lung, with a spreading form resembling a malignant pleural mesothelioma mainly occupying the pleural cavity. Based on positive staining method with specific monoclonal antibodies against G-CSF, it was considered that the leukocytosis was caused by G-CSF producing tumor.
We report a 74-year-old woman with cervical cancer who developed pulmonary cryptococcosis which presented as a solitary focal ground-glass opacity (GGO) on high-resolution computed tomography (HRCT). Serial HRCT showed the progression from the GGO to a discrete solid nodule. We hypothesize that the initial GGO may correspond pathologically to partial filling of air spaces with cryptococcal organisms and inflammatory cells. To our knowledge, this is the first report of pulmonary cryptococcosis with a solitary focal GGO on HRCT in the literature.
A 54-year-old woman complained of fever and hepatosplenomegaly. The pathological findings of a liver biopsy specimen revealed the infiltration of lymphocytes in the sinusoids and that of the laparoscopically resected spleen revealed the infiltration of lymphocytes in the red pulp, which was positive for CD3, CD43, CD45RO and T-cell intracellular antigen-1 (TIA-1) and was negative for βF1, while the white pulp was spared. Genetic analysis of the spleen cells revealed the rearrangement of T-cell receptor (TCR) Cβ1, Jδ1 and Jγ. Epstein-Barr virus (EBV) genomic DNA was detected in the spleen cells. Atypical lymphocytes appeared in the peripheral blood and bone marrow, chromosomal analysis revealed del (13) (q12 q14), trisomy 8 and breakage of RB gene. Elevated level of serum vascular endothelial growth factor (VEGF) was observed. Hepatosplenic γδ T cell lymphoma (GDTL) was diagnosed. The patient was treated with chemotherapy by cyclophosphamide, hydroxydoxorubicin, vincristine and prednisolone (CHOP), however, it was ineffective, and the patient died of hemorrhage from the lymphoma involvement of the intestine 5 months after the onset of disease.
We report a 55-year-old man who showed no change after chemotherapy for chronic myelogenous leukemia-blastic crisis (CML-BC) in 1998. Allo-peripheral blood stem cell transplantation (PBSCT) was then performed and Complete remission (CR) was achieved, but recurrence was seen in 2001. Imatinib administration brought about partial remission (PR) and then a reduced intensity stem cell transplantation (RIST) was performed. The bcr-abl gene disappeared and Ph1 chromosome disappearance was ascertained. CR was thus achieved. There are still no established radical methods of treating CML-BC. Thus, therapy by allograft after the patient has entered hematological remission with imatinib is considered a new way of dealing with cases of CML-BC.
We report a 72-year-old man with Waldenström’s macroglobulinemia (WM) in whom diffuse large B-cell lymphoma (DLCL) occurred 17 years after the diagnosis of WM. The malignant cells of both DLCL and WM expressed CD20 on their surface. CHOP plus anti-CD20 monoclonal antibody, rituximab, were effective for both diseases, and the patient remains disease-free 17 months later.
We report a patient with rheumatoid arthritis (RA) who developed malignant lymphoma of the diffuse large B-cell type in the right submandibular region shortly after initiation of oral methotrexate (MTX). Despite cessation of MTX, the lymphadenopathy did not regress, and only reached complete remission after 3 courses of CHOP therapy followed by irradiation. In this patient highly active RA itself was considered to be the main cause of malignant lymphoma, and MTX might have contributed to the development by modifying the immune system. When RA is highly active, MTX should be used carefully because of the possible development of malignant lymphoma as well as other serious complications.
A 60-year-old woman with systemic sclerosis (SSc) was admitted because of severe anemia and Raynaud’s phenomenon. Her anemia was associated with a low serum haptoglobin level and positive results of direct Coomb’s tests, which indicated the presence of autoimmune hemolysis. Other laboratory investigations revealed positive anti-nuclear antibodies, anti-topoisomerase antibody, cold agglutinins, as well as low serum levels of IgM, C3, C4 and CH50. Bone marrow aspiration showed discrete hyperplasia of the erythropoietic system. She was diagnosed as low-titer cold agglutinin disease rousing secondarily to SSc. The anemia was alleviated with the oral administration of prednisolone. This case emphasized, in terms of pathogenesis, the close association between systemic rheumatic diseases and hematological abnormalities evoked by autoimmunity.
A 64-year-old Japanese woman with a two-week history of polyarthralgia and persistent cough was diagnosed as seropositive polyarthritis and fulfilled the criteria of early rheumatoid arthritis (RA). In addition, inflammatory pitting edema of the distal extremities was apparent, suggestive of the remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A number of investigations including hand MRI, bone scintigraphy and HLA typing supported a diagnosis of RS3PE syndrome rather than RA. Chest computed tomography revealed concomitant evidence of bronchiolitis obliterans organizing pneumonia (BOOP). Treatment with 30 mg of prednisolone daily immediately ameliorated the polyarthritis and the BOOP. Seropositive polyarthritis with distal pitting edema may be categorized as both RA and the RS3PE syndrome.