In Japan parasitic diseases have been considered to be successfully controlled in the last 30 years. However, some parasitic diseases, such as food-borne zoonoses and/or larva migrans, are emerging and/or re-emerging in Japan. Furthermore, imported parasitic diseases like malaria are also gradually increasing. Unfortunately accurate numbers of parasitic diseases other than echinococcosis, malaria, amebiasis, giardiasis, or cryptosporidiosis are obscure in Japan because of the lack of a legal registration system. Since symptoms and diagnostic imaging patterns of parasitic diseases are non-specific and have similarities with other infectious diseases or cancer, parasitic diseases are sometimes overlooked or left misdiagnosed. In this review, the current status of parasitic diseases in Japan is briefly summarized based on the analysis of the accumulated cases seen in our department. We also outline the clinical features, differential diagnosis and treatment of representative parasitic diseases for the better understanding and managementof the parasitic diseases in Japan.
(Internal Medicine 42: 222-236, 2003)

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Recent progress in development of molecular cancer therapeutics revealed new types of antitumor drugs, such as Herceptin, Gleevec, and Iressa as potent therapeutics for each specific tumor. We have been working on molecular cancer therapeutics, and in particular, those related to drug resistance, Here, I describe several resistance mechanisms, including apoptosis regulation, cellular stress response and cellular survival signals which have show close relevance to drug resistance. Pglycoprotein (P-gp) is the key molecule in multidrug resistance (MDR) and a good target for chemotherapy. Proteasome is involved in the resistance mechanismto topo II-targeted chemotherapy in solid tumors. Apoptosis program in tumor cells plays a critical role in chemotherapy- induced tumor cell killing, and the blockade of the apoptosis-inducing pathway could be another mechanism for drug resistance. Glyoxalase I is a molecule involved in apoptosis resistance mechanism in tumors. Survival (antiapoptosis) signals are the good targets for various antitumor drugs to over comeinnate drug resistance. Our present studies provide novel targets for effective molecular cancer therapeutics in future.
(Internal Medicine 42: 237-243, 2003)

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Objective We studied the relationship between the polyacrylamide gel electrophoresis (PAGE) pattern of lipoproteins and other indicators of lipid metabolism.
Materials and Methods Fasting serum lipid was analyzed in 108 Japanese hyperlipidemic and normolipidemic subjects (39 males and 69 females, 63.5±6.4 years old). We classified the lipoprotein profile by PAGE into the following four types (SAND); Type S (symmetric), Type A (asymmetric), Type N (nodular), and Type D (disrupted). The relationship between WHO classification of hyperlipidemias and SAND classification was analyzed.
Results Normolipidemicsubjects were classified into Types S, A, and N. Type IIa subjects were classified into Types S, A, and N. Type IIb subjects were classified into Types S, A, N, and D. Type IV subjects were classified into Types N and D. Serum total cholesterol (TC) was not different among the SAND types, but serum triglyceride (TG) was significantly different among the types. Serum TG tended to increase from Type S to Type D. VLDL cholesterol (C) increased from Type S to Type D. LDL-C showed a trend to decrease from Type S to Type D, but without significance. HDL-C significantly decreased from Type S to Type D. VLDL-TG, LDL-TG, and HDL-TG increased from Type S to Type D. TC/TG, HDL-C/TG, LDL-C/LDL-TG, and HDL-C/HDL-TG ratios all significantly decreased from Type S to Type D. However, VLDL-C/VLDL-TG was not different among the groups.
Conclusion SAND classification of lipoprotein profile may offer a new clinical tool to cover the weak point of WHO classification.
(Internal Medicine 42: 244-249, 2003)

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Objective Chronic active EBV infections (CAEBV) are often causative of malignant lymphoproliferative disorders, such as natural killer (NK) cell-lineage granular lymphocyte proliferative disorders (NK-GLPD), which are refractory to several conventional chemotherapies and usually show a poor prognosis. To explore the possibility of preventive treatment for Epstein-Barr virus (EBV)-infected NK-GLPD, we examined the effect of antiviral drugs on EBV-infected pre-malignant NK cells.
Methods EBV-infected pre-malignant NK cells (P-NK cells) were isolated from the periphery of a patient suffering from severe hypersensitivity to mosquito bites (SHMB). Abnormal oligoclonal expansion of EBV-infected CD56(+)/CD3(-) NK cells was observed in her periphery. Effects of several antiviral drugs were examined both on the proliferation and on EBV-replication of P-NK cells.
Results Vidarabine and foscarnet, but not acyclovir nor gancyclovir, significantly suppressed both the proliferation and EBV-DNA replication of P-NK cells in a dose-dependent manner, whereas these drugs did not suppress the proliferation of YT, which is an EBV-infected malignant NK cell line. The combination of vidarabine and foscarnet had an additive effect and almost completely suppressed the proliferation of P-NK cells.
Conclusion The present results indicate that vidarabine and/or foscarnet may be effective for preventive treatment of EBV-associated NK-GLPD.
(Internal Medicine 42: 250-254, 2003)

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Objective The aim of this study was to clarify the characteristics of transient ischemic attack (TIA) patients with atrial fibrillation (AF) compared to those without.
Methods We divided 67 TIA patients with left hemispheric involvement into two groups; patients with AF (AF group) and without AF (Non-AF group) and compared the clinical characteristics between the two groups.
Patients AF group included 12 patients (73.0±9.7 years old) and the Non-AF group 55 patients (64.1±9.8 years old).
Results Clinically, arterial disease was less frequently seen in the AF group than in the Non-AF group (17% vs 53%, p=0.028). No significant differences were observed between the two groups in the duration (<1 hour; AF vs Non AF group: 50% vs 32%) or number of TIAs (more than 1; 17% vs 37%), use of anticoagulation or antiplatelet at time of symptomonset (34% vs 14%), past history of stroke and TIA (58% vs 38%) and ischemic heart diseases (8% vs 13%), and risk factors for atherosclerosis including hypertension (42% vs 71%), diabetes mellitus (17% vs 31%), hyperlipidemia (17% vs 47%), smoking (50% vs 51%) and other emboligenic cardiac diseases except for AF (0% vs 4%). Aphasia was observed more frequently in the AF group than in the Non-AF group (67% vs 20%, p=0.003), whereas, hemiparesis without aphasia was seen less frequently in the AF group than in the Non-AF group (17% vs 55%, p=0.025).
Conclusion TIA patients with AF are more likely than those without AF to exhibit a major hemispheric syndrome, such as aphasia.
(Internal Medicine 42: 255-258, 2003)

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The endoscopic examination of a 66-year-old male patient revealed a protruding lesion close to a reddish lie area in the antrum of the stomach. The protruding lesion and reddish area were resected completely with endoscopic mucosal resection using an insulation-tip diathermic knife (IT-EMR). Histological examination of the protruding lesion revealed proliferation of fibroblasts and infiltration of inflammatory cells, and it was diagnosed as an inflammatory fibroid polyp (IFP). Adenocarcinoma in the lie area was present adjacent to the IFP. This maybe the first report of gastric cancer concomitant with gastric IFP treated by endoscopic mucosal resection.
(Internal Medicine 42: 259-262, 2003)

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Gastric inflammatory fibroid polyps (IFPs) are rare benign lesions that occur in the distal stomach. We describe a 70-year-old woman with Helicobacter pyloripositive gastric IFP treated with eradication. Gastroduodenal endoscopy revealed a pyramidal-shaped, broadbased tumor with an ulcerated apex at the antrum. Helicobacter pylori was positive by both histology and tissue culture, and eradication (a proton pump inhibitor, amoxicillin, and clarithromycin) was performed. After 3 months, the tumor morphologically changed and the apex ulcer was markedly enlarged. This case suggests that H. pylori may play a role in the pathophysiology of IFPs.
(Internal Medicine 42: 263-267, 2003)

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A young man with repetitive deep venous thrombosis of the legs and the inferior vena cava, and his family were eventually diagnosed by means of molecular genetic analysis as having both hereditary protein C and protein S deficiency. There have been a few reports of families with combined protein C and protein S deficiency and only one report of such a family characterized at the DNA level. This was the first reported family in Japan with combined deficiency of protein C and protein S accompanied by segregation of gene lesions.
(Internal Medicine 42: 268-272, 2003)

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A 67-year-old woman presented with open-ring enhancement on MR images in the thoracic spinal cord. Steroid therapy improved the patient's paraplegia, but six months later she developed left hemiparesis and a new open-ring enhancement appeared in the right cerebrum. Despite high-dose methylprednisolone therapy and plasmapheresis, another lesion appeared at the middle portion of the left centrum semiovale. Stereotaxic brain biopsy demonstrated active demyelination characteristics of multiple sclerosis (MS). This case indicates that open-ring enhancement can help differentiate MS from nondemyelinating disease, and that MS showing ring enhancement may contribute to disease severity and need more intensive immunomodulatory therapies.
(Internal Medicine 42: 273-276, 2003)

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We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.
(Internal Medicine 42: 277-280, 2003)

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