Flow cytometric DNA analysis provides rapid, quantitative objective information regarding the biological behavior of urological malignancies. Moreover, clinical applications of the many recent advances made the flow cytometry are expected to materialize soon. For instance, flow cytometric DNA ploidy analysis for human bladder cancers may provide a significant diagnostic and prognostic potential. Also, flow cytometric DNA analysis of irrigation specimens produces a higher sensitivity than conventional cytology for detecting bladder cancer. However, there are obvious pitfalls with this approach since diploid or near-diploid tumors cannot always be recognized by DNA analysis alone. One of the most significant advantages possible with flow cytometry is its capability of analyzing simultaneously multiple parameter on single cells. The integration of the DNA content with proliferative activity should yield important information significant to the biological behavior of individual tumors. Flow cytometric DNA/bromodeoxy-uridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients. Therefore, multiparameteric flow cytometric analysis can be used to isolate specific tumor cells from mixed cell populations, and should receive even increased attention as a valuable diagnostic technique and prognostic factor. In the present review, the efficacy of flow cytometric DNA ploidy analysis integrated with cell proliferation markers is discussed.

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Accumulating evidence has shown that functional recoveries in various kinds of animal models of neurodegenerative diseases can be achieved by grafting fetal neurons into the brain. On the basis of these successful results, clinical trials are under way to determine whether human fetal mesencephalic tissue can ameliorate motor functions in patients with Parkinson's disease. Recent autopsy findings of parkinsonian patient implanted with human fetal mesencephalic tissue clearly revealed that the fetal neuronal graft can survive for extended period of time in the human brain and densely reinnervate the surrounding host striatal tissue. It is, however, still important to obtain more practical, effective and ethically justifiable donor material for the future clinical application of the procedures. Desirable properties for the donor cells include long-term survival in the host brain, neuronal cell type for the reconstruction of damaged neural circuits, and susceptibility to genetic manipulation for the practical use. With the development of molecular biology techniques, genetic modification and transplantation of the donor neuronal cells might be a feasible way to cure many kinds of central nervous system diseases toward a “graft-gene therapy”.

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Oxidized-low density lipoprotein (ox-LDL) exhibits various atherogenic properties, such as the formation of foam cells, the recruitment of macrophages into arteries, the promotion of cell growth, the formation of thrombi, and the development of vasoconstriction. Antioxidants inhibit atherosclerosis in cholesterol-fed animals by preventing the recruitment of macrophages into the arteries suggesting that oxidation is important for such recruitment of macrophages, and that it is responsible for early development of atherosclerosis. Calcification and an increase in extracellular matrix (ECM) are frequently observed in advanced atherosclerosis. These processes are active and regulated, not passive and degenerative, and do not appear to be controlled by ox-LDL. The control of calcifications and ECM increase will provide new directions in the treatment of atherosclerosis especially in the advanced stages. Future treatment should include strategies to inhibit the calcification and the increase in ECM.

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This article reviews current topics in neuroleptic-induced extrapyramidal symptoms in Japan, focusing especially on the clinical features of akathisia and dystonia. Akathisia is a common side effect associated with antipsychotic drugs. It is most commonly characterized by subjective inner restlessness and objective motor signs, especially in the lower extremities. The mechanisms underlying akathisia remain unclear and controversial; however, an increase in the activity of β-adrenergic systems relative to dopaminergic systems has been hypothesized, based on clinical therapeutic observations that β-blocking agents are effective in this condition. A Japanese version of the Barnes Akathisia Scale has recently been established and uses a standardized videotape method for its precise evaluation. Various acute and chronic manifestations of neuroleptic-induced dystonia have been reported in Japan, including blepharospasm, difficulty in opening the eye lids, torticollis, retrocollis, oculogyric crisis, and Pisa syndrome. This review also introduces several other topics related to drug-induced extrapyramidal symptoms in Japan. These include; 1) the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), which has recently been established, 2) studies on the discontinuation of anticholinergic drugs, and 3) a summary of extrapyramidal symptoms induced by drugs other than neuroleptics.

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Human melanoma antigens and their epitopes recognized by T cells have been identified using a variety of methods. These antigens are classified as 1) melanocyte specific melanosomal proteins (MART-1, gp100, tyrosinase and TRP-1), 2) proteins expressed in testis and a variety of cancers (MAGE-1, MAGE-3, BAGE and GAGE), 3) tumor specific mutated proteins (β-catenin, MUM-1 and CDK4), and 4) others (p15). Some of the HLA-A2 binding non-mutated melanoma epitopes contained non-dominant anchor amino acids and have relatively low HLA-A2 binding affinity, suggesting that these epitopes were likely to be subdominant or cryptic self determinants. The significant correlation observed between vitiligo development and IL2 based immunotherapy suggested that autoreactive T cells specific for these self peptides were involved in melanoma regression in vivo. In addition, since adoptive transfer into patients of CTL recognizing these epitopes resulted in tumor regression, these epitopes may be tumor rejection antigens. Melanoma reactive CTL were efficiently induced from PBL of patients by in vitro stimulation with PBMC pulsed with these melanoma epitopes and may be useful in adoptive transfer protocols for the treatment of patients with metastatic melanoma. An immunization trial using the MART-1 and gp100 peptides in conjunction with incomplete Freund's adjuvant is in progress. These identified antigens may be useful for the development of new immunotherapies for the treatment of melanoma patients as well as for understanding the mechanisms of anti-tumor immune responses and autoimmune disorders against melanocytes.

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Heparin effects were studied on Lewis rats with α₁ antitrypsin (AT) defect. Among 8 rats that were born at the same birth, three rats were shown to have mild defect of α₁ AT. Heparin was injected repeatedly into all the 8 rats. Interstitial pneumonia and localized periodic acid-Schiff (PAS) stain of hepatocytes were found in α₁ AT defective male. One of the three α₁ AT defective rats had about a half of normal α₁ AT level. Antithrombin (AT) III level was slightly low in the α₁ AT defective female with splenomegaly. Lung electron micrograph of the other α₁ AT defective female showed edematous changes of capillaries and alveolar basement membranes and also proliferated collagen fibers. In the lung of α₁ AT defective male, many thrombocytes adhered to alveolar degenerated smooth muscles that were recognized as Masson bodies. Extracted platelet-activating factor (PAF) in the plasma of the α₁ AT defective male was shown to trigger T lymphocyte chemotaxis. Five normal Lewis rats were immunized with bovine serum albumin (BSA). IgG1 antibody to BSA was produced in all the rats. The rats with high titers of IgG1 anti BSA antibody showed more strongly atrophic changes of glomerulus than those of the mild α₁ AT defective rats treated with heparin.

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A 45-year-old woman with acute lymphoblastic leukemia (ALL) who failed to achieve complete remission (CR) after one course of induction chemotherapy with vincristine, daunorubicin, prednisolone and 1-asparaginase was successfully treated with a high dose of cytosine arabinoside (Ara-C) and mitoxantrone. The leukemic blasts were CD7, 19, 33, and 38 antigens positive, and had a rearrangement in the T-cell receptor δ chain gene. The karyotype was normal. Primary induction failure and positivity for myeloid antigens are both reported to be poor prognostic factors for ALL. Nevertheless, this patient was successfully treated with the high dose Ara-C and mitoxantrone, and she remains in CR for over 20 months. Combination chemotherapy with high dose Ara-C and mitoxantron may be of benefit for refractory ALL with both CD7 and myeloid antigens.

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