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Biomedical subjects

T Yoshino

Publications and source records attributed to T Yoshino.

At least 19 recordsLinked to original sources

Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms.

Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.

Adolescent↗

Endoscopic submucosal dissection for early gastric cancer: results and degrees of technical difficulty as well as success.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a new method for the curative treatment of early gastrointestinal neoplasms, which was developed in order to increase the en bloc and R0 resection rate, especially for lesions larger than 20 mm in diameter. Drawbacks of ESD include the fact that it is technically a substantially more difficult procedure and that it is associated with a higher perforation rate. A retrospective study was therefore carried out to analyze cases in relation to the procedure time and resection success, and these factors were correlated with the characteristics of the lesions. PATIENTS AND METHODS: From January 2002 to November 2005, 196 lesions in 185 patients with early gastric cancer were treated using ESD in our hospital. The rates of curative en bloc resection, the incidence of perforation, and the procedure times were analyzed in relation to lesion size (small, 20 mm or less in diameter; large, over 20 mm), location (upper, middle, or lower third of the stomach) and the presence or absence of ulceration. RESULTS: The rate of curative en bloc resection was 84 % (93 % of the lesions overall were resected in one piece), with a perforation rate of 6.1 % (all perforations were managed endoscopically) and a mean procedure time of 68 min. The rate of curative en bloc resection differed significantly depending on the location of the lesion (upper vs. middle vs. lower, 74 % vs. 77 % vs. 91 %; P < 0.05), as well as on the size of the lesion (> 20 mm vs. 20 mm or less, 59 % vs. 89 %; P < 0.0001). There were also significant differences in the mean procedure times in relation to the location of the lesion (upper vs. middle vs. lower, 105 min vs. 81 min vs. 45 min; P < 0.0001) and the size of the lesion (> 20 mm vs. 20 mm or less, 124 min vs. 55 min; P < 0.0001), as well as the presence of ulceration (positive vs. negative, 97 min vs. 65 min; P < 0.05). With regard to perforation rates, significant differences were also observed in relation to the location of the lesion (upper vs. middle vs. lower, 22.6 % vs. 2.8 % vs. 3.2 %; P < 0.0005) and size of the lesion (> 20 mm vs. 20 mm or less, 16.2 % vs. 3.8 %; P < 0.005). No local recurrences of curatively resected lesions (n = 119) were observed after a follow-up period of 1 year. CONCLUSIONS: The difficulty of ESD depends on the location and size of the lesion, as well as on the presence of ulceration. We would recommend that trainees should begin by carrying out ESD on lesions with a diameter of less than 20 mm without ulceration that are located in the lower third of the stomach.

Adult↗

Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis.

BACKGROUND: Prostaglandin (PG)D(2) and E(2), two major cyclooxygenase (COX) products, are generated by PGD(2) synthase (PGDS) and PGE(2) synthase (PGES), respectively, and appear to mediate airway inflammation. OBJECTIVE: We sought to determine the role of PGDS and PGES in the pathophysiology of chronic rhinosinusitis (CRS). METHODS: The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and five subjects without sinusitis. Immunohistochemistry and quantitative real-time PCR were used to evaluate the expression. RESULTS: Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG2+ eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non-asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively. CONCLUSIONS: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.

Adolescent↗

Primary effusion lymphoma with skin involvement.

Primary effusion lymphoma (PEL) was once defined as a body cavity-based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67-year-old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.

Aged↗

Magnetic-field-induced band-structure change in CeBiPt.

We report on a field-induced change of the electronic band structure of CeBiPt as evidenced by electrical-transport measurements in pulsed magnetic fields. Above approximately 25 T, the charge-carrier concentration increases nearly 30% with a concomitant disappearance of the Shubnikov-de Haas signal. These features are intimately related to the Ce 4f electrons since for the non-4f compound LaBiPt the Fermi surface remains unaffected. Electronic band-structure calculations point to a 4f-polarization-induced change of the Fermi-surface topology.

Journal Article↗

Identification of Ki23819, a highly potent inhibitor of kinase activity of mutant FLT3 receptor tyrosine kinase.

Constitutively active internal tandem duplication (ITD) in the juxtamembrane domain of Fms-like tyrosine kinase 3 (FLT3), a type III receptor tyrosine kinase, is the most common molecular defect associated with acute myeloid leukemia. Its presence confers a poor outcome in patients with acute myeloid leukemia who receive conventional chemotherapy. FLT3-ITD has therefore been considered to be an attractive molecular target for a novel therapeutic modality. We describe here the identification and characterization of Ki23819 as a novel FLT3 inhibitor. Ki23819 suppressed proliferation and induced apoptosis of FLT3-ITD-expressing human leukemia cell lines. The growth-inhibitory effect of Ki23819 on MV4-11 cells was superior to that of SU11248, another FLT3 inhibitor (IC(50)<1 vs 3-10 nM). Ki23819 inhibited the autophosphorylation of FLT3-ITD more efficiently than that of wild-type FLT3. FLT3-ITD-dependent activation of the downstream signaling proteins ERK and STAT5 was also inhibited within similar concentration ranges. Thus, Ki23819 is a potent in vitro inhibitor of FLT3.

Acute Disease↗

Nasal exposure to Staphylococcal enterotoxin enhances the development of allergic rhinitis in mice.

BACKGROUND: Staphylococcal enterotoxins (SEs) appear to play a role in the pathogenesis of allergic disease. However, little is known whether the nasal exposure to SE affects the development of allergic rhinitis (AR). OBJECTIVE: We sought to determine the in vivo effect of nasal exposure to SE on the development of AR using mouse model. METHODS: BALB/c mice were intranasally sensitized with Schistosoma mansoni egg antigen (SmEA) in the presence or absence of staphylococcal enterotoxin B (SEB). Control mice were intranasally sensitized with either SEB or SmEA alone. The production of antigen-specific antibodies including IgE, nasal eosinoplilia and cytokines by nasal mononuclear cells was compared among mice that had or had not received SEB treatment. RESULTS: Nasal exposure to SEB enhanced the development of AR in SmEA-sensitized mice, as manifested by SmEA-specific IgE production, nasal eosinophilia, and IL-4 and IL-5 production by nasal mononuclear cells after Ag challenge. This treatment also elicited IFN-gamma production by SmEA-primed cells. In addition, these mice produced SEB-specific IgE whereas mice treated with SEB without SmEA sensitization did not produce SEB-specific IgE or demonstrate nasal eosinophilia. CONCLUSION: These results suggest that the nasal exposure to SEB enhances susceptibility to AR although the exposure to SE solely does not induce AR.

Allergens↗

Characterization of allergen-specific monocyte-derived dendritic cells generated from monocytes by a single-step procedure: effect on naïve and memory T cells.

BACKGROUND: Dendritic cells are one of the most potent antigen-presenting cells and when pulsed with allergen can modulate allergen-specific T-cell responses. We sought to establish a single-step method by which to generate allergen-specific monocyte-derived dendritic cells (MoDCs). METHODS: Dermatophagoides farinae (Df)-prepulsed MoDCs were generated from monocytes by culturing with Df in the presence interleukin (IL)-4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF)-alpha simultaneously. Df-prepulsed MoDC were incubated with autologous naive and memory T cells in the absence of recall antigen, then proliferation and cytokine production by T cells was determined. RESULTS: Generation of allergen-prepulsed MoDCs was confirmed by examining expression of surface molecules. Df-prepulsed MoDC selectively induced proliferation of Df-specific T cells in the absence of recall antigen. Under these conditions, Df-prepulsed MoDCs augmented but did not alter the cytokine production profile. In addition, Df-prepulsed MoDCs activated naive T cells leading to proliferation and selective production of IFN-gamma in allergic patients but not in healthy subjects. CONCLUSIONS: These results suggest that Df-prepulsed MoDC generated from monocytes by a simple single-step manipulation can induce Df-specific cellular responses from both naive and memory T cells in the absence of recall antigen, and these cells potentially can be utilized as immune adjuvants in allergen-specific immunotherapy.

Adult↗

Axillary apocrine carcinoma with benign apocrine tumours: a case report involving a pathological and immunohistochemical study and review of the literature.

BACKGROUND: Apocrine carcinoma is rare and often occurs in the axilla. This is the second apocrine carcinoma arising in bilateral axillae with associated apocrine hyperplasia to be reported. AIMS/METHODS: Because benign apocrine tumours may be precursors of cancer, this case was investigated immunohistochemically and histologically, and a literature (English and Japanese) review undertaken of cases with coexistent malignant and benign apocrine tumours in the axilla to elucidate the relation between apocrine carcinoma and benign apocrine tumours. RESULTS: Only four cases of axillary apocrine carcinoma with benign apocrine tumours were identified in the literature. In each case, benign apocrine hyperplasia was situated within and surrounding the adenocarcinomatous nests. Staining for epithelial membrane antigen revealed three patterns: (1) poorly differentiated tumour cells showing strong cytoplasmic staining; (2) combined luminal surface and cytoplasmic staining of glandular cells; and (3) a strongly positive lineal staining pattern at the luminal membrane surface, comprising one or two apocrine hyperplastic secretory cells. The basal lesions of apocrine hyperplasia were strongly positive for alpha smooth muscle actin, whereas the periphery of adenomatous lesions showed weaker positive staining, even though the periphery of adenocarcinomatous lesions was negative. CONCLUSIONS: All five apocrine carcinomas with benign apocrine tumours occurred in elderly Japanese men who had bilateral benign apocrine tumours even if affected by unilateral axillary apocrine carcinoma. The immunohistochemical results support the notion that apocrine hyperplasia is a precursor of cancer and that apocrine carcinoma, adenoma, and hyperplasia may be successive steps in the linear progression to carcinoma.

Adenocarcinoma, Papillary↗

Pathology review for paediatric non-Hodgkin's lymphoma patients in Japan; a report from the Japan association of childhood leukaemia study (JACLS).

A central pathology review system with an immunophenotyping laboratory was established in Japan to support the clinical trial, the Japan Association of Childhood Leukaemia Study (JACLS) NHL-98, for patients with paediatric non-Hodgkin's lymphoma (NHL). Pathology samples from 155 clinically-suspected NHL cases were evaluated centrally initially using the Revised European-American Lymphoma (REAL) classification in a rapid review (within 2 weeks after surgery/biopsy) and then later at the consensus review (once a year). The samples were subsequently re-classified according to the new World Health Organisation (WHO) classification. After the pathology review, 96 (62%) patients were eligible for the study, and 58 of them (60%) had extra-nodal primaries. These NHL cases included B-cell lymphomas (precursor B-cell, 11; Burkitt, 18; diffuse large B-cell, 18; not otherwise specified, 3) and T/Natural Killer (NK)-cell lymphomas (precursor T-cell, 23; anaplastic large cell, 20; others, 3). There was excellent concordance in making the diagnoses (95/96, 99%) and typing (93/96, 97%) of NHL between the rapid and consensus reviews. Five cases, initially diagnosed as diffuse large B-cell lymphoma by the review, were re-classified as Burkitt lymphoma according to the immunocytochemical criteria by the WHO classification. A total of 59 (38%) cases were excluded from the study: they were Hodgkin lymphoma (7), leukaemias (11), reactive lymphoid hyperplasia (20), necrotizing lymphadenitis (7), no consensus diagnosis (1), insufficient materials (2), and others (11). This is the first report of the central pathology review from the paediatric NHL group study in Japan. Because various diseases, either neoplastic or reactive, mimicked NHL, clinically and histopathologically, the central pathology review system was critical and essential for patient enrollment and protocol assignment in our clinical trial. Through the two-step review system, highly reliable data were generated to support this study.

Adolescent↗

Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome.

BACKGROUND: Serotonin (5-HT) syndrome is the most serious side effect of antidepressants. Although several drugs have been used for the treatment of 5-HT syndrome, a universal pharmacotherapy has not been established. NMDA receptor antagonists have been reported to have neuroprotective effects. In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model. METHODS: 5-Hydroxy-l-tryptophan (100 mg/kg) and clorgyline (2 mg/kg) were administered intraperitoneally in rats to induce 5-HT syndrome. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior hypothalamus were measured using a microdialysis technique. RESULTS: In the group pretreated with saline, the rectal temperature increased to more than 40 degrees C, and all of the animals died within 90 min of the drug's administration. The NA and 5-HT levels in the anterior hypothalamus increased to about 15- and 1100-fold of the pre-administration levels, respectively. Pretreatment with risperidone (0.5 mg/kg) and ketanserin (5 mg/kg) prevented the development of hyperthermia and the increase in the NA level. Memantine (10 mg/kg) and MK-801 (0.5 mg/kg) also prevented the development of hyperthermia and the increase in the NA level. These results suggest that NMDA antagonists, as well as potent 5-HT (2A) antagonists, may be effective drugs for the treatment of 5-HT syndrome. CONCLUSIONS: Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.

5-Hydroxytryptophan↗

Chromoendoscopy using indigo carmine dye spraying with magnifying observation is the most reliable method for differential diagnosis between non-neoplastic and neoplastic colorectal lesions: a prospective study.

BACKGROUND AND AIMS: Differential diagnosis between non-neoplastic and neoplastic lesions is very important at colonoscopy, since removal or biopsy of non-neoplastic polyps wastes time and resources. We therefore conducted a prospective study to examine whether indigo carmine dye spraying with and without magnification is more reliable than the conventional method for differential diagnosis. PATIENTS AND METHODS: 122 patients with 206 lesions of 10 mm or smaller were recruited into this study. All lesions detected on colonoscopy were first diagnosed using the conventional view, then at chromoendoscopy using 0.2 % indigo carmine, and finally at chromoendoscopy with magnification. The diagnosis at each step were recorded consecutively. All lesions were finally categorized as neoplastic or non-neoplastic according to pit pattern; non-neoplastic lesions were biopsied for histological evaluation, and all the neoplastic ones were removed endoscopically. The accuracy rate of each type of endoscopic diagnosis was evaluated, using histological findings as reference. RESULTS: Histologically, 46 lesions (22 %) were non-neoplastic and 160 (78 %) were neoplastic. The overall diagnostic accuracies by conventional view, chromoendoscopy, and chromoendoscopy with magnification were 84.0 % (173/206), 89.3 % (184/206) and 95.6 % (197/206), respectively. CONCLUSION: Chromoendoscopy with magnification is the most reliable method for determining whether a colorectal lesion is non-neoplastic or neoplastic.

Adult↗

Immunohistochemical evaluation of a malignant intestinal carcinoid in a dog.

An intestinal carcinoid with multiple metastases was identified in a 5-year-old male Shih Tzu with a clinical history of anemia, fatigue, anorexia, vomiting, intermittent diarrhea, intestinal bleeding, and progressive emaciation. There was a yellowish-white mass 15 mm in diameter in the anterior jejunum and white nodules consistent with metastases in many organs. Histopathologically, the mass consisted of neoplastic cells arranged in lobules, trabeculae, or closely interdigitating islands of cells. Neoplastic cells were generally polygonal with round hyperchromatic nuclei, modest amounts of eosinophilic cytoplasm, and eosinophilic cytoplasmic granules. Mitoses were common. Rosette formations of tumor cells were apparent in metastatic tumors. Immunohistochemically, tumor cells stained positive for cytokeratin 13, synaptophysin, protein gene product 9.5, neuron-specific enolase, chromogranin A, calcitonin gene-related peptide, serotonin (5-HT), and Leu-7. Serum 5-HT concentrations for this dog were increased 10-fold compared with those of normal dogs. All findings were consistent with a diagnosis of a malignant intestinal carcinoid.

Animals↗

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.

Animals↗

High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases.

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.

Aged↗

Lymphomatous polyp of mantle cell type in the duodenum complicated by gastric cancer: a case of trisomy 3 and t(11;14)(q13;q32).

We experienced a rare case of a lymphomatous polyp of mantle cell type forming a polypoid mass lesion in the duodenum bulbous together with advanced gastric cancer. A total gastrectomy was performed, and the specimen revealed atypical small- to medium-sized lymphoid cells with indented nuclei, which infiltrated the Peyer's patch and formed a nodular mass in the lamina propria and submucosa of the duodenum. The lymphoma cells also infiltrated the lymphoid follicle of the gastric mucosa, spleen, and regional lymph node with a typical mantle zone pattern. Flow cytometric analysis of the single cells of the lymph node and immunohistochemistry of a paraffin-embedded specimen revealed that the lymphoma cells expressed surface CD5, CD19, CD20, and nuclear cyclin D1. Chromosomal analysis of this single cell suspension revealed that these lymphoma cells have trisomy 3 in conjunction with t(11;14)(q13;q32), which is frequently seen in mucosa-associated lymphoid tissue lymphomas (MALToma) in the stomach and is also reported in mantle cell lymphoma as a secondary genetic alteration. Our report suggests that trisomy 3 may be a common chromosomal abnormality in lymphomatous polyps of mantle cell type.

Adenocarcinoma↗

Clonal expansion of limited T cell clonotypes in affected muscle from a patient with post-transplant polymyositis.

Critical roles of T cells in idiopathic polymyositis have been suggested, but, those in polymyositis occurring as GVHD after BMT are poorly understood. We thus investigated T cell clonality in a patient with post- transplant polymyositis. As a result, T cell receptor beta chains used various BV families in peripheral blood, but only one BV family (BV7) in affected muscle. Importantly, T cells proliferated oligoclonally both in the peripheral blood and the muscle, however, the expanded clonotypes were completely different. Taken together, T cells expanded in the muscle, possibly stimulated by limited kinds of antigens, may drive myositis.

Adult↗