Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 127 records · Page 7Linked to original sources

PubMed1995

Polymorphic reticulosis is a neoplasm of large granular lymphocytes with CD3+ phenotype.

BACKGROUND: Polymorphic reticulosis, a type of lethal midline granuloma (LMG), has been referred to as nasal T-cell lymphoma (NTL) because of its proliferating cells' positive reactivity to anti-T-lymphocyte antibodies. Recently, several studies have suggested that proliferating cells in NTL may be natural killer (NK) in nature. NK cells and human nonmajor histocompatibility-restricted cytotoxic T-lymphocytes have the morphology of large granular lymphocytes (LGL) (i.e., a high cytoplasmic:nuclear ratio and cytoplasmic granules). Whether NTL-LMG possesses an LGL morphology is examined in this study. METHODS: Two lymph node smears, peripheral blood showing a leukemic picture, and an electron microscope (EM) examination of a cutaneous lesion, respectively, were obtained from four patients with NTL-LMG. Immunohistochemical examination of the proliferating cells and of the Epstein-Barr virus (EBV) genome by both polymerase chain reaction and in situ hybridization also were performed. RESULTS: All patients presented with necrotic and granulomatous lesions in the upper respiratory tract. Histology showed polymorphous cellular infiltrates containing large atypical cells with positive reaction to CD3 (three patients), CD43 (two patients), CD45RO (two patients), and OPD4 (one patient). Imprint smears revealed azurophilic large membrane-delimited granules in an ample cytoplasm, which was confirmed by EM. The presence of the EBV genome in the tumor cells was observed in one patient. CONCLUSION: The current findings showed that NTL-LMG or polymorphic reticulosis is a proliferation of LGL with a CD3+ phenotype.

Adult↗

PubMed1995

Efficient induction of chromosome-type aberrations by topoisomerase II inhibitors closely associated with stabilization of the cleavable complex in cultured fibroblastic cells.

Eukaryotic topoisomerase II (Topo-II) inhibitors such as etoposide, adriamycin and mitoxantrone, which commonly stabilize the cleavable complex of the enzyme and DNA, have been found to efficiently induce chromosome-type aberrations (mainly breaks and exchanges) in cultured Chinese hamster lung fibroblastic cells (CHL cells). To clarify whether the induction of chromosome-type aberrations is mediated by stabilization of the cleavable complex, the present study investigated (1) the correlation between the induction of chromosome-type aberrations and the amount of cleavable complex formed; and (2) the ATP dependence of the Topo-II inhibitor-induced chromosome-type aberrations due to the ATP requirement of cleavable complex formation by Topo-II. First, in cells treated with the Topo-II inhibitors, (etoposide, adriamycin) and aclarubicin, an antagonist of the inhibitor of cleavable complex formation, the frequency of chromosome-type aberrations decreased dose-dependently with aclarubicin, in contrast to an increase of chromatid-type aberrations. The formation of the cleavable complex was further established by a proteinase K/SDS precipitation assay for cleaved double-strand DNA in a cell-free system and in CHL cells. Results from both experiments showed that aclarubicin caused a dose-dependent suppression of the accumulation of the cleavable complex induced by etoposide, which corresponded particularly well to the reduction of chromosome-type aberrations in etoposide-treated cells. In ATP-depleted cells simultaneously treated with etoposide and dinitrophenol (DNP), chromosome-type aberrations were reduced as compared with DNP-untreated cells, in contrast to an increase of chromatid exchanges in the cells. This means that etoposide-induced chromosome-type aberrations in ATP-depleted cells may be attributable to incompleteness of Topo-II activities to form DNA double-strand breaks. The present findings indicate that the stabilization of the cleavable complex on Topo-II is closely associated with the induction of chromosome-type aberrations.

2,4-Dinitrophenol↗

PubMed1995

Fatigue resistance of composite restorations: effect of filler content.

OBJECTIVES: The purpose of this study was to evaluate the effects of filler level on the fatigue impact resistance of resin composite. METHODS: A series of experimental composite materials was prepared by incorporating a silanized quartz filler (3-5 microns in size) into a light-cured resin matrix of Bis-GMA/TEGDMA. The filler contents in the experimental composites varied from 40 to 85 wt%. The composites were placed in standardized Class I cavities prepared in bovine teeth. The specimens were stressed with a repetitive impact load (1.6 x 10(2) joule) with loading cycles ranging from 50,000 to 150,000 times. The cracks induced by cyclic loading were observed on the sectioned surfaces of the tested specimens. RESULTS: The composites with considerably low or high filler content (< 60% or > 80% by weight) were significantly low in fatigue resistance. The results revealed that an inverse linear relationship tended to exist between filler level and fatigue resistance of the composite materials beyond a certain level of filler content. SIGNIFICANCE: Increased filler level does not necessarily improve the fatigue resistance of a resin composite as determined by applying a repetitive impact load.

Animals↗

PubMed1995

Enhancing effects of diphenyl dimethyl dicarboxylate on serum antibody production in BALB/c mice.

The effects of diphenyl dimethyl dicarboxylate (PMC) on serum antibody production were investigated in BALB/c mice. PMC (3 and 6 mg/kg/d, respectively) was orally administered to the mice for 14 consecutive days. The effects on antibody production were assessed by enzyme-linked immunosorbant assay (ELISA) of immunoglobulin (Ig) subset levels in serum, collected at week 2 from mice with or without immunization by an i.p. injection of 0.1 mg ovalbumin (OVA) in complete Freund's adjuvant (CFA) at week 1 after the first oral administration of PMC. PMC showed a significant enhancement of the levels of total serum IgG, IgG1, IgG2a and IgA without the immunization, while total IgE levels were not affected. When mice were immunized with OVA after the oral administration of PMC, moreover, a marked stimulation of antibody production was observed in mice fed 6 mg/kg/d PMC, hardly accompanied with increase of IgE levels. In these mice, additionally, PMC significantly elevated anti-OVA IgG (including both IgG1 and IgG2a mediated by different T-helper cells) levels. These findings indicate that PMC enhances antibody production in mice with therapeutic concentrations that have shown great promise in the treatment of chronic hepatitis virus of type B.

Animals↗

PubMed1995

Oral tolerance to ovalbumin in mice as a model for detecting modulators of the immunologic tolerance to a specific antigen.

Oral tolerance is thought to have a role in preventing allergic responses and immune-mediated diseases. Modulation of this tolerance by drugs and chemicals can cause or suppress them. An improved model of oral tolerance to ovalbumin (OVA) in mice was developed to detect modulators of the tolerance and to apply it to selected immunomodulating substances, cyclophosphamide (CP), Escherichia coli lipopolysaccharide (LPS) and cadmium chloride (Cd). Male C3H/HeN mice given an oral administration of 20 mg OVA were immunized 7 d later with an i.p. injection of 0.1 mg OVA in complete Freund's adjuvant. Effects of oral OVA and agents on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected 7 or 14 d after immunization. Oral tolerance was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. It was primarily associated with the decreased serum levels of anti-OVA IgG (including both IgG1 and IgG2a subclasses regulated differently by T-helper subpopulations, Th2 and Th1 cells, respectively). The C3H model of oral tolerance was further examined to detect modulators of the tolerance. An i.p. injection of CP prior to oral OVA, or 5 consecutive daily oral administrations of LPS after oral OVA elevated or reduced serum levels of anti-OVA IgG in C3H mice hyposensitized by the oral OVA, respectively. Concerning IgG subclasses, CP restored anti-OVA IgG2a but not IgG1 levels, while LPS caused greater suppression of both anti-OVA IgG1 and IgG2a levels. Oral administrations of Cd for 5 d after oral OVA also suppressed anti-OVA IgG1 levels further.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

PubMed1995

Immunologic type of thyroid lymphoma in an adult T-cell leukemia endemic area in Japan.

Our previous study showed that thyroid non-Hodgkin's lymphoma (TL) in an adult T-cell leukemia/lymphoma (ATL) non-endemic area were exclusively B-cell derived. The present study was carried out to examine whether TL in an ATL endemic area are also exclusively of B-cell type. Eight cases with TL admitted to the hospital situated in an ATL endemic area were studied: they were all female with an age range from 50 to 75 (median 67) years. Histologically four of the eight cases showed a follicular pattern. Immunophenotypic study revealed all but one case to be of B-cell nature: CD3-, 4-, 8-, 20+, 22+, 45RA+, 45RO-, L22-, L24+/-, L28+. Neoplastic cells in one case with the histology of diffuse large cell lymphoma showed a CD3+, 4+, 8-, 20-, 22-, 45RA-, 45RO+/-, L22-, L24-, L28-, indicating a helper T-cell phenotype. Genotypic study showed rearrangement of T-cell beta-chain receptor in this case. This case also had antibodies against HTLV-1 in the serum. This case shows that it is also possible to develop T-cell TL in an endemic ATL area.

Aged↗

PubMed1995

Sporadic activation of Epstein-Barr virus in thyroid lymphoma.

The causal role of Epstein-Barr virus (EBV) in the development of B-cell lymphoma, especially in immunocompromised individuals, has been suggested. The purpose of the present study was to evaluate an association of EBV with thyroid lymphoma (TL) and chronic lymphocytic thyroiditis (CLTH) which is known to play an important role in the development of TL. Thirty cases with TL and 28 with CLTH were studied for presence or absence of EBV genome in the lesions using the polymerase chain reaction (PCR) and the in situ hybridization method. EBV genomes were detected by PCR in one and two cases with CLTH and TL, respectively. Subtyping of EBV genome was possible in one TL case showing B-type in EBNA-2 coding region. In situ hybridization revealed positive signals in the nucleus of lymphoma cells, which also expressed latent membrane protein-1. The present findings indicate that activation of EBV in TL is not common.

Adolescent↗

PubMed1995

Angiomatous lesions in the wall of chronic pyothorax.

Formation of massive hematoma in the cavity of chronic pyothorax (CP) has been described previously, but its mechanism remained unclear. In the present study of 99 cases, the vascular lesions in the wall of CP were examined by histological methods, including immunohistochemistry. The age of patients ranged from 42 to 80 years (mean 57 years), with a male to female ratio of 3.3. Histologically the CP wall was covered by a fibrin layer containing cellular debris and red blood cells. Directly beneath the fibrin layer, a fibrous layer of varied thickness was present that extended to the subserosal tissue or so-called fat plane defined by computed tomography. At the junctional region between the fibrin and fibrous layer, angiomatous lesions were observed in 33 cases (Group I). In the fibrin layer of this group, dilated vessels frequently bulged into the pleural cavity. In another two cases, closely packed large vessels with irregularly thickened walls resembled an arteriovenous fistula (Group II). In seven patients, histologic specimens showed a total necrosis. The remaining 57 cases without the findings in Groups I and II were categorized as Group III. These findings suggested that formation of angiomatous lesion preceed intrapleural bleeding, which occasionally progressed to form a massive hematoma.

Adult↗

PubMed1995

Modification of mu-opioid agonist-induced locomotor activity and development of morphine dependence by diabetes.

We examined the locomotor-enhancing action of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), and physical dependence on morphine in diabetic and nondiabetic mice. Morphine (5-20 mg/kg, s.c.) and DAMGO (1-4 nmol, i.c.v.) had a dose-dependent locomotor-enhancing effect in both nondiabetic and diabetic mice. The locomotor-enhancing effects of morphine and DAMGO were significantly less in diabetic mice than in nondiabetic mice, and were significantly reduced after pretreatment with either beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist, or naloxonazine (35 mg/kg, s.c.), a selective mu1-opioid receptor antagonist. Both diabetic and nondiabetic mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor nondiabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3-10 mg/kg, s.c.). Several withdrawal signs, such as weight loss, diarrhea, ptosis, jumping and body shakes, were observed after naloxone challenge in morphine-dependent nondiabetic mice. Although morphine-dependent diabetic mice showed greater weight loss than nondiabetic mice, the incidence of jumping and body shakes after naloxone challenge in diabetic mice were lower than that in nondiabetic mice. These results suggest that diabetic mice are selectively hyporesponsive to mu1-opioid receptor-mediated locomotor enhancement. Furthermore, diabetes may affect mu1-opioid receptor-mediated naloxone-precipitated signs of withdrawal from physical dependence on morphine.

Animals↗

PubMed1995

The presence and subtype of Epstein-Barr virus in B and T cell lymphomas of the sino-nasal region from the Osaka and Okinawa districts of Japan.

BACKGROUND: Association between Epstein-Barr virus (EBV) and human malignancies, including sino-nasal lymphoma (SNL), has been suggested. EBV-associated malignancies have been reported to show distinct geographic distribution. EXPERIMENTAL DESIGN: In the present study, the presence of an EBV genome and its subtypes (type A and B) were examined in 52 cases of sino-nasal lymphomas of B and T cell type collected from two areas of Japan: Osaka, situated on the mainland, and Okinawa, islands situated in a southwest part of Japan with a subtropical climate. Our previous epidemiologic study showed that the frequency of nasal T cell lymphoma was 3.5 times higher in Okinawa than in Osaka. RESULTS: There were no prominent differences in age distribution or sex ratio between these two areas: age ranged 8 to 85 (median 54) years, with a male to female ratio of 1.26:1. Immunophenotypically, 27 cases were B cell type (20 Osaka, 7 Okinawa), 20 were T cell type (9 Osaka, 11 Okinawa), and 5 were undefined. By PCR, EBV positivity in throat washings of normal individuals in Osaka and Okinawa was 52 and 53%, respectively, with marked preponderance of subtype A in both areas. EBV genome was found in 6 of 15 cases (40%) and 4 of 5 cases (80%) of nasal B and T cell lymphomas in Osaka and in 3 of 7 cases (43%) and 7 of 7 cases (100%) in Okinawa, showing the different frequencies of positivity by immunophenotype but not by district. All but one patient had type A EBV. The in situ hybridization confirmed the results of PCR as positive signals in the nucleus of proliferating cells. Latent membrane protein-1 was expressed in 13 of 22 cases (59%). CONCLUSIONS: These findings suggest that EBV, exclusively type A, might be a causative factor in sino-nasal lymphoma of not only T cell but also B cell type in Japan.

Adolescent↗

PubMed1995

Effect of diabetes on the morphine-induced inhibition of gastrointestinal transit.

The effect of diabetes on the morphine-induced inhibition of gastrointestinal transit was examined in mice. Morphine dose-dependently inhibited gastrointestinal transit after s.c. administration in both non-diabetic mice and diabetic mice. There was no significant difference between the ED50 values for this antitransit effect of morphine in non-diabetic and diabetic mice. The gastrointestinal antitransit effect of morphine was significantly antagonized by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.), a selective mu-opioid receptor antagonist, in both non-diabetic and diabetic mice. However, pretreatment with naloxonazine (35 mg/kg, s.c.), a selective mu 1-opioid receptor antagonist, had no effect on the antitransit properties of morphine. These results suggest that diabetes failed to alter the mu 2-opioid receptor-mediated antitransit effect of morphine.

Animals↗

PubMed1995

Role of Epstein-Barr virus in pleural lymphomagenesis.

Longstanding inflammation in chronic pyothorax (CP) plays a role in the development of pleural lymphoma; therefore, in 1987, the term pyothorax-associated lymphoma (PAL) was proposed. A recent study showed in the tumor cells of a limited number of patients, the presence of the Epstein-Barr virus (EBV) genome together with the expression of latent infection genes in the tumor cells of PAL. The purpose of the present study is to evaluate an association of EBV with PAL in a large number of patients. In addition, the presence of the EBV genome was examined in cases with CP without PAL. Histologic, immunohistochemical studies, and analyses by polymerase chain reaction (PCR) and in situ hybridization method for EBV were performed on 34 PAL and 16 CP collected by nationwide study. Median age of the patients in both diseases was approximately 70 years with a marked preponderance in men. Mean duration of CP in patients with CP alone and with CP complicated with PAL was 33 and 37 years, respectively. Histologically all PAL were non-Hodgkin's lymphoma, with immunoblastic type being the most common. Immunohistochemistry revealed 28 of 34 PAL to be B-cell type. Combined PCR, in situ hybridization method, and immunohistochemistry showed that the EBV genome was detected in lymphoma cells in 85% of PAL with almost constant expression of latent membrane protein-1. The EBV genome was detected by PCR in only one of 16 CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Expression of vascular endothelial growth factor and its receptor mRNA in angiosarcoma.

BACKGROUND: Vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells in vitro, can be angiogenic factor in vivo. VEGF is known to be produced by several tumor cells and plays an important role for neovascularization in tumor tissue. Recently, tyrosine kinase encoded by the flt gene was identified as a receptor for VEGF. Angiosarcoma (AS) is a rare malignant tumor that arises from endothelium. At present, little is known about a mechanism of proliferation of the AS. EXPERIMENTAL DESIGN: In an immunohistochemical study of 99 cases of AS, 11 cases showing a positive reaction for anti-VEGF Ab were selected for the present study. In these cases, expression of VEGF and its receptor (flt) mRNA was examined by in situ hybridization: sense and antisense probes for VEGF and flt mRNA were used. RESULTS: In situ hybridization study with antisense probes revealed that the VEGF mRNA was expressed in AS cells and mononuclear cells in all but one case. Intensity of VEGF staining by immunohistochemistry correlated well with VEGF mRNA expression. The flt mRNA was expressed in AS cells in all 10 cases that were positive for VEGF mRNA. Sense probe for VEGF and flt mRNA gave no positive reactions. CONCLUSIONS: These findings suggest a presence of paracrine or autocrine mechanism of proliferation in AS through VEGF and its receptor flt.

Aged↗

PubMed1994

Purification and characterization of a protein that binds to metal responsive elements of the human metallothionein IIA gene.

Metal responsive element (MRE) is a cis-acting DNA motif located in the upstream region of vertebrate metallothionein genes, which can confer metal responsiveness on downstream heterologous promoters. A protein that binds to the MRE sequence in a zinc-dependent manner (zinc regulatory factor; ZRF) was purified 16,000-fold from HeLa cell nuclear extracts by means of the avidin-biotin method, in which a complex formed between ZRF and a biotinylated probe containing MRE was trapped by streptavidin-agarose beads, and ZRF was recovered by salt extraction. By repeating the method three times, a homogeneous 116-kDa protein was obtained whose recovery was zinc-dependent and MRE sequence-specific. UV cross-linking analysis also revealed that a protein that specifically binds to MRE has the same molecular mass as the purified protein. Zinc-dependent and MRE sequence-specific footprints of ZRF were obtained on MREa and MREb in the upstream region of the human metallothionein IIA gene. The ZRF-MRE complex dissociates by the addition of chelating reagents, suggesting a direct role of zinc ions in the DNA binding of ZRF. Partial amino acid sequences of ZRF were found to be highly homologous to those of a mouse MRE-binding protein, mMTF-1.

Amino Acid Sequence↗

PubMed1994

Effects of diabetes on the morphine-induced Straub tail reaction in mice.

The effects of diabetes on the morphine-induced Straub tail reaction were examined in mice. The Straub tail reaction induced by s.c. administration of morphine was significantly less in diabetic mice than in non-diabetic mice. The morphine-induced Straub tail reaction was significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. Furthermore, the morphine-induced Straub tail reaction was also significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine, a selective mu1-opioid receptor antagonist. These results suggest that mice with diabetes are hypo-responsive to mu1-opioid receptor-mediated Straub tail reaction.

Animals↗

PubMed1994

A staging system for soft-tissue sarcoma and its evaluation in relation to treatment.

In order to define the significant factors for a staging system of soft-tissue sarcomas (STS), histologic and clinical findings in 190 adult patients with localized STS in the extremities and trunk were reviewed. The male-to-female ratio was 1.21. The histologic grading of tumors was defined according to the criteria recently proposed by us: tumors were low-grade in 65 cases, intermediate-grade in 57 cases and high-grade in 68 cases. The initial surgical procedure was as follows: intracapsular excision in 9 cases, marginal excision in 104 and wide local excision in 77, including 15 amputations. The mode of treatment was surgery alone (101 patients), surgery and chemotherapy (58), surgery and radiotherapy (22) and surgery and combined chemo- and radiotherapy (9). Univariate analysis revealed histologic grade, sex, tumor size and tumor depth to be significant prognostic factors. Multivariate analysis revealed histologic grade to be the only independent factor for prognosis. Significant clinical factors in each histologic grade were then evaluated. In the low-grade group, local recurrence significantly affected prognosis. Most of the patients with local recurrence had had marginal resection as the initial surgical procedure. No clinical factors affecting prognosis in the intermediate-grade group could be determined. In the high-grade group, patients with wide local excision and adjuvant chemotherapy had a better prognosis than those with marginal excision with or without adjuvant chemotherapy and wide local excision without chemotherapy (p = 0.09). In conclusion, histologic grade was the only significant factor for the staging of STS. On the basis of our staging system, different modalities of treatment for each grade of STS might be indicated; adequate surgery is essential for the prevention of local recurrence, which resulted in reduced mortality in patients with low-grade STS. For high-grade STS, the prevention of distant metastasis by combined extensive surgery and adjuvant chemotherapy may make long-term survival possible.

Adult↗

PubMed1994

Epstein-Barr virus in patients with polymorphic reticulosis (lethal midline granuloma) from China and Japan.

BACKGROUND: Polymorphic reticulosis is one of several diseases constituting lethal midline granuloma (LMG). Previous immunohistochemical studies suggested a T-cell nature of proliferating cells; the term nasal T-cell lymphoma (NTL-LMG) has since been used widely. The authors' previous study in Asian countries showed the clustering of Mongolian patients with NTL-LMG, but the frequency varied with geographic area; it was much higher in Korea and southwest Japan (Okinawa) than in Shanghai and Honshu, Japan. Recently an etiologic role of Epstein-Barr virus (EBV) for the development of NTL-LMG has been postulated. METHODS: In this study, the presence of EBV and human T-cell lymphocytic leukemia virus type 1 (HTLV-1) genomes were examined in NTL-LMG patients from Southwest Japan (Okinawa, 10 patients), another Japanese district (Honshu, 21 patients), and Shanghai, China (5 patients). All of the tissues from different geographic sites were analyzed at one central location. RESULTS: Immunohistochemistry showed that proliferating large cells were positive for CD43 and/or CD45RO, identical with reported NTL-LMG cases. Polymerase chain reaction (PCR) revealed the presence of EBV genome in the NTL-LMG lesions, but the frequency varied according to the geographic area: 67% in Okinawa, 33% in Honshu, and 100% in Shanghai. In situ hybridization provided positive signals in the nuclei of proliferating cells. Expression of latent membrane protein in the proliferating cells of cases positive for EBV by PCR and in situ hybridization was confirmed. CONCLUSIONS: The results suggest that the EBV may play a role in the development of NTL-LMG. However, the variation of frequency of EBV genome in different geographic locations suggests that EBV infection may not be an indispensable condition for the disease.

Adolescent↗

PubMed1994

Lethal midline granuloma in Okinawa with special emphasis on polymorphic reticulosis.

Lethal midline granuloma (LMG) is a clinical term used to describe a condition which may be manifested histologically as Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a neoplastic proliferation of lymphoreticular cells. In this report, twenty-two cases of LMG in Okinawa were examined. The frequency of LMG per 100,000 outpatients of the ear, nose and throat clinic in Okinawa was 67, and the higher frequency of PR (27) and ML (34) in Okinawa than in other districts of Japan was characteristic. Polymerase chain reaction, in situ hybridization, and immunohistochemical studies showed that the proliferating cells in PR were CD43+ and simultaneously contained Epstein-Barr viral genome in their nuclei. The higher frequency of PR and ML in Okinawa is discussed in conjunction with a review of pertinent literature: multiple factors including genetic, viral environmental, and socioeconomic factors seem to affect the frequencies of these diseases.

Adult↗