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Biomedical subjects

N Ikegami

Publications and source records attributed to N Ikegami.

At least 37 records · Page 2Linked to original sources
PubMed1996

Protective effects of Ca2+ channel blockers against methyl mercury toxicity.

The protective effects of Ca2+ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca2+ channel blockers (20 mg/kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca2+ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1, 25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 microM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 microM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca2+ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca2+ plays an important role in the mechanisms of methyl mercury toxicity.

Animals↗
PubMed1996

A case for the adoption of pharmacoeconomic guidelines in Japan.

In recent years, more and more Japanese pharmaceutical companies have been submitting pharmacoeconomic data to the government, following the official request that such data may help in setting pharmaceutical prices. The companies have cooperated because, by doing so, they could influence pricing decisions for new products. However, the quality of these data at present is considered to be poor and heavily biased. The introduction of pharmacoeconomic guidelines that outline a set of standardised factors to be included in evaluations are necessary, so that an appropriate comparison of the cost effectiveness of the many new drugs that are introduced into the Japanese market each year can be made. In addition to supporting the development of standardised guidelines, the Ministry of Health and Welfare should clarify how pharmacoeconomic data are to be used to aid policy decisions and also mandate the publication of pharmacoeconomic data.

Drug Costs↗
PubMed1995

Health care without managed care in Japan.

The best gross health indices in the world and universal coverage with no overt signs of rationing characterize the Japanese health care system. The delivery system, which consists primarily of private physicians and private hospitals, is functionally independent, but the financing system is strictly regulated. The author argues that this combination is the key to the system's unique success.

Cost Control↗
PubMed1994

Propagation of JC virus in human neuroblastoma cell line IMR-32.

JC virus (JCV), the causative agent of a human demyelinating disease, progressive multifocal leukoencephalopathy, has a very narrow host range. Cells permissive for infection by JCV have been essentially limited to primary human fetal glial cells, which are difficult to obtain and maintain. In pilot studies, it was found that JCV can multiply in an established cell line of human neuroblastoma. JCV strains Mad-1 and Tokyo-1 were inoculated, respectively, into two cell lines, IMR-32 (neuroblastoma) and A-172 (glioblastoma). Viral infection with cytopathic effect was observed only in IMR-32 cells, and the most efficient viral proliferation was obtained in cells cultured in medium containing 2% fetal calf serum (FCS). Both Mad-1 and Tokyo-1 strains propagated well, with the former being more efficient than the latter. Viral replication was confirmed by immunofluorescence, electron microscopy, and a hemagglutination assay. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and Western blot analysis of the purified virus revealed the characteristic JCV protein profile. Thus, IMR-32 cells have been found to be permissive for JCV, which should provide a useful system for further studies of virus proliferation and viral tissue tropism.

Blotting, Western↗
PubMed1994

Applying RUG-III in Japanese long-term care facilities.

A U.S. nursing home case-mix system, Resource Utilization Group, Version III (RUG-III), was tested in a variety of Japanese long-term care facilities. Staff time and resident characteristics were measured for a sample of 871 patients. Acceptable reliability was found for items defining RUG-III, and the system explained 44% of the variance in wage-weighted staff time (cost). Also, Japanese and U.S. costs had similar patterns across RUG-III categories. However, there was wide discrepancy between the stated purpose of Japanese facilities and their patient populations, and the current payment mechanism did not reflect actual use of resources.

Aged↗
PubMed1994

Pharmaceutical prices, quantities and innovation. Comparing Japan with the US.

Per capita expenditure on pharmaceuticals is higher in Japan than in the US, despite a series of drug price reductions instigated by the Japanese Ministry of Health and Welfare that began in 1981. For some individual products, these price reductions cumulatively totalled more than 50%. This article argues that although the price of individual drugs is lower in Japan than in the US, aggregate expenditure is higher because of the greater use of newly-introduced original drugs and lower use of generics. Providers and consumers also tend to use drugs in larger quantities in Japan, because of polypharmacy and greater use of vitamins and nutrients, antihypertensives, cerebral metabolic activators (e.g. idebenone) and milder-acting drugs (i.e. drugs with low toxicity but unproven clinical efficacy). The level of expenditure is unlikely to decline, despite changes to pricing policy and ongoing efforts to improve the pharmaceutical distribution system and to discourage physician dispensing activities.

Cross-Cultural Comparison↗
PubMed1994

[A case of bronchogenic cyst in the esophageal wall].

A 73-year-old man with a right aortic arch was admitted because of stridor and dyspnea. We diagnosed a cervico-mediastinal cyst associated with bilateral recurrent laryngeal nerve palsy. Median sternotomy revealed a cystic tumor located in the esophageal wall. Microscopic examination of the resected cyst showed cartilage, smooth muscle and mucous gland, so the final diagnosis was bronchogenic cyst. The bilateral recurrent laryngeal nerve palsy was caused by chronic pressure from the cyst. Mediastinal cysts should be found and treated as early as possible, because these cysts may sometimes cause fatal complications.

Aged↗
PubMed1993

DNA-sequence rearrangement required for the adaptation of JC polyomavirus to growth in a human neuroblastoma cell line (IMR-32).

Infection of a human neuroblastoma cell line (IMR-32) with the JC polyomavirus (JCV) strain Mad-1 with subsequent serial passage results in the generation of a virus adapted to growth in IMR-32 (K. Akatani, M. Imai, M. Kimura, K. Nagashima, and N. Ikegami, J. Med. Virol., in press). To understand the basis of this adaptation, we molecularly cloned JCV DNAs from the adapted virus. The cloned JCV DNAs consisted of essentially three species (M1-IMRa, -IMRb, and -IMRc) with rearranged regulatory regions. Two TATA sequences are present in the regulatory region of the parental virus Mad-1, but one distal from the origin of replication was commonly deleted in M1-IMRa, -IMRb, and -IMRc. We showed that these regulatory regions were required for the efficient growth of JCV in IMR-32. Various JCV strains should be propagated in IMR-32, if their regulatory regions are replaced with those defined in this study. Since it is difficult to propagate JCV in cells other than primary human fetal glial cells, this system may be useful for structural and immunological studies of JCV.

Adaptation, Biological↗
PubMed1993

Three cases of juvenile onset HTLV-I-associated myelopathy with pseudohypoparathyroidism.

Among 201 patients diagnosed with HAM/TSP at Kagoshima University, 21 juvenile onset patients had manifested clinical signs and symptoms at less than 15 years of age. They appeared to have common characteristics such as short stature and slight mental retardation. These signs prompted us to investigate five of them endocrinologically; and three patients with pseudohypoparathyroidism (PHP) were confirmed. Serum calcium levels were low, and human parathyroid hormone (PTH) infusion (Ellsworth-Howard test) caused low response in urinary cyclic AMP and phosphorus excretion. The first case had IgA nephropathy, which is generally associated with infectious diseases, while the second case had muscular lymphocytic infiltration. The mothers of cases 1 and 2, who were both seropositive for HTLV-I, were suspected to have abnormal calcium metabolism based on Ellsworth-Howard test. A brother of case 1 and two sisters of case 3 had also HAM/TSP and short stature. The early clinical onset of HAM/TSP may be due to PTH receptor anomaly and a low level of 1,25-dihydroxyvitamin D, which is deficient in PHP and is involved in the regulation of the immune response. The association with IgA nephropathy or myositis may result from progressive HTLV-I infection.

Adult↗
PubMed1993

An autoaggressive process against bystander tissues in HTLV-I-infected individuals: a possible pathomechanism of HAM/TSP.

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a well-defined clinico-pathological entity in which the virus infection and the host immune responses are involved in the pathomechanism. It is generally agreed that the virus infection precedes the development of HAM/TSP and the infection is persistent during the course of disease. However, what plays the key role for the development of HAM/TSP remains to be elucidated. In this article, we emphasise the importance of the unique nature of HTLV-I-infected cells, which may have a potential ability to produce viral antigens outside of the blood flow, and we also review a variety of evidences supporting the following proposal. In our hypothesis, the supply of infected T cells from blood flow to central nervous system (CNS) is primary for the development of CNS lesions. Both anatomically determined hemodynamic conditions and adhesion molecule-mediated interactions between circulating infected T cells and endothelial cells may contribute to the localization of the main lesions. Following an induction of the HTLV-I antigens on the surface of infected T cells in CNS compartment, expansion of the responses of immunocompetent T cells against the viral proteins may result in CNS tissue damage which may be mediated by released cytokines. This is the first attempt to implicate a bystander damage mechanism in a human disease as an essential pathomechanism.

Autoimmunity↗
PubMed1993

Hepatitis C virus infection in children with hemophilia: characterization of antibody response to four different antigens and relationship of antibody response, viremia, and hepatic dysfunction.

We studied hepatitis C virus (HCV) infection in children with hemophilia by characterizing the antibody responses to four different HCV antigens and investigating the relationship of the antibody response to viremia and hepatic dysfunction. Three antigens (core, nonstructural (NS) 3, and NS5) were expressed in Escherichia coli transfected with plasmids that contained fragments of the putative core and of the NS3 and NS5 regions of the HCV genome, respectively. Antibody responses to these three antigens and the commercially available C100 antigen were detected by enzyme-linked immunosorbent assay. In 45 children with hemophilia, the percentage of children with seropositivity for C100, core, NS3, and NS5 protein in one or more specimens was 82%, 91%, 91%, and 89%, respectively. The time course of changes in the antibody response to the four antigens was determined by using sera obtained from 44 of the 45 patients at intervals of 1 to 4 years. Antibodies to the core and NS3 antigens appeared earlier and persisted longer than those to C100 and NS5 after HCV infection. The relationship of antibody response to viremia and hepatic dysfunction was investigated in 27 children by using the polymerase chain reaction assay. Five children whose tests results were negative for all four antigens did not have viremia or hepatic dysfunction; 13 of the 16 children with positive results for the four antigens had both viremia and hepatic dysfunction. Five of the six children whose serum had the core and NS3 antibodies but not either C100 or NS5, or both, had viremia, and three of them also had hepatic dysfunction. These results suggest that detection of antibodies to the core and NS3 antigens is useful for the serologic diagnosis of HCV infection and that both antibodies are more related to viremia than are the antibodies to C100 and NS5. In addition, viremia is strongly associated with hepatic dysfunction.

Adolescent↗
PubMed1993

A Ki-1-positive cell line expressing Epstein-Barr virus antigens, established from a child with Ki-1-positive lymphoma.

We report here the establishment of a CD30 (Ki-1) antigen-positive cell line 'Ki-JK' from a child with anaplastic large cell lymphoma. We characterized this cell line and show that: (i) Ki-JK cells do not grow in soft agar but infrequently produce a tumor or suppressed growth when injected into nude mice; (ii) Ki-JK cells expressed Epstein-Barr virus (EBV) antigens, EBV-associated nuclear antigen-2 and latent membrane protein; (iii) Ki-JK cells are labelled by in situ hybridization using an RNA probe derived from the BamHI W fragment of EBV, and (iv) polymerase chain reaction demonstrates the presence of an EBV BamHI W sequence in DNA of lymphoma and Ki-JK cells. These results suggest an etiological role for EBV in the development of some cases of Ki-1-positive lymphomas.

Adolescent↗