Experimental autoimmune myocarditis is provoked by immunization with cardiac myosin. This animal model finally develops into dilated cardiomyopathy through repetitive myosin injections. To identify the myocardiogenic epitope, therefore, it is imperative not only to understand the mechanismof induction, but also to produce specific therapies, such as a blocking therapy to suppress the autoimmune process. Thus, we attempted to identify the myocarditogenic epitope using recombinant peptides. β-cardiac myosin heavy chain (CMHC)was amplified from rat mRNAby a reverse transcription polymerase chain reaction method. The PCR primers were designed to narrow the epitopic amino acid portion from each N-terminal to C-terminal site. These PCR products were cloned into an E. coli expression vector to produce fusion proteins consisting of a Histidine-tag and a myosin peptide. The segment of amplified CMHC including the epitopic amino acid sequence to provoke moderate myocarditis in vivo was reported previously. Each peptide solution was emulsified in an equal volume of complete Freund's adjuvant and given as an immunization to 7-week-old rats. On day 21 after immunization, the rats were sacrificed, and the fresh heart was observed pathologically. Through this immunization, we could restrict the myocardiogenic site. Lastly, this peptide was found to be located on residues from 1, 124 to 1, 153. Using ELISA, the antibodies against myocarditogenic peptides were easily identified. Whether or not the antibody productivity is linked to myocarditogenecity is discussed.
(Internal Medicine 42: 3-6, 2003)

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Pancreatic β-cells are strongly engaged in protein secretion and have highly developed endoplasmic reticulum (ER). Proper folding of polypeptide into a three-dimensional structure is essential for cellular function and protein malfolding can threaten cell survival. Various conditions can perturb the protein folding in the ER, which is collectively called ER stress. In order to adapt ER stress conditions, the cells respond in three distinct ways such as transcriptional induction of ER chaperones, translational attenuation, and ER-associated degradation (ERAD). However, when ER functions are severely impaired, the cell is eliminated by apoptosis via transcriptional induction of CHOP/GADD153, the activation of CJUN NH₂-terminal kinase, and/or the activation of caspase-12. Recent studies have revealed that β-cell is one of the most susceptible cells for ER stress, and ER stress-mediated apoptosis in β-cells can be a cause of diabetes. A comprehensive understanding of the impact of the ER stress pathway in β-cells and how it relates to the development of diabetes may contribute to provide new targets for the prevention and treatment of this disease.
(Internal Medicine 42: 7-14, 2003)

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Many studies have confirmed that the long term use of biological agents targeting TNFα in therapy for rheumatoid arthritis give rise to sustained improvement in symptoms and signs of disease provided the anti-TNF agent is efficacious and of low immunogenicity. The current regimes for infliximab 3 or 10 mg/kg infusion in combination with weekly oral methotrexate, or of subcutaneous etanercept 25 mg twice per week fulfil these criteria. D2E7, a 'human' antibody produced by phage display, has also demonstrated efficacy in clinical trials. It has recently emerged that anti-TNF therapy protects joints from structural damage. One year data for infliximab and methotrexate combination therapy suggest that this regime reduces disability. In early RA, etanercept acts morerapidly than methotrexate to decrease symptoms and retard progression of erosions. In conclusion, for patients with established and early RA, anti-TNF therapies set a new standard for symptom control and joint protection.
(Internal Medicine 42: 15-20, 2003)

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Objective The purpose of this study was to evaluate the prognostic and clinical significance of newly acquired complete right bundle branch block (CRBBB) in airline pilots.
Patients This study included pilots with acquired CRBBB, identified from a group of over 2, 700 Japan Airline pilots. When the pilots applied for employment, a past medical history, physical examination, electrocardiogram, and chest radiograph were obtained. The pilots with ECG abnormality including CRBBB were not included in the study because of hiring requirements.
Results Thirty-six pilots with CRBBB were identified between 1983 and 2002. All pilots with CRBBB were evaluated for the presence of ischemic heart disease by treadmill exercise testing, echocardiogram and exercise thallium scintigraphy. Twelve individuals underwent coronary angiography. The mean age of pilots was 44.4 ±5.8 years. The mean observation period was 10.9±5.7 years. For each of the 36 study subjects, Holter electrocardiogram and echocardiogram were obtained every 6 months after the CRBBB was detected. Exercise stress testing was performed every year. Exercise thallium scintigraphy was performed every 2 years to detect ischemic heart disease. During the observation period, two pilots stopped flying temporarily because of frequent ventricular premature beats and one pilot stopped flying permanentaly because of atrial fibrillation. During the follow-up period, no cardiovascular events were observed in pilots with CRBBB who had no underlying ischemic heart disease.
Conclusion Acquired CRBBB does not confer a poor prognosis, particularly in young men working as a pilot if there is no evidence of ischemia on exercise stress testing, echocardiography and exercise thallium scintigraphy.
(Internal Medicine 42: 21-24, 2003)

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Objective To evaluate the clinical features, etiology, and prognosis of patients who required long-term mechanical ventilation (LMV)of over three months for respiratory failure following underlying disease, and observation of their clinical course until death.
Patients Thirty-seven patients (27 males, 10 females) treated in the internal and medical intensive care unit at Kawasaki Medical School Kawasaki Hospital over the 16-year period from April 1985 to March 2001 were retrospectively studied.
Results Many of these patients were elderly males with respiratory disease such as pulmonary emphysema or old pulmonary tuberculosis, which had developed into acute respiratory failure resulting in respiratory tract infection and initiation of mechanical ventilation. The survival rates of one year, three years and five years after the start of mechanical ventilation were 60%, 30%, and 16%, retrospectively, and the prognoses were poor. Respiratory tract infection was the most common and serious complication. Specifically, ventilator-associated pneumonia (VAP) was a complication in 21 patients and also the main cause of death. VAP was observed 2.3 years after the initiation of mechanical ventilation with significant differences in the following risk factors being observed between VAP(+) and VAP(-) groups: chronic obstructive pulmonary disease, duration of mechanical ventilation, prior antibiotics, aspiration of gastric contents and use of histamine-type II receptor antagonist. The causative pathogens of VAP were Pseudomonas aeruginosa and Staphylococcus aureus, which were frequently isolated from tracheal aspirates. All patients with VAP caused by MRSA died shortly after contracting the infection.
Conclusions This study has demonstrated that appropriate treatment for respiratory tract infections such as VAP and the prevention of nasocomial infection due to MRSA is of paramount importance for patients requiring long-term mechanical ventilation of over three months.
(Internal Medicine 42: 25-32, 2003)

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Objective Epstein-Barr virus (EBV), a lymphotropic herpes virus causing infectious mononucleosis (IM), also causes various central nervous system (CNS) infections. In the present study, EBV CNS infections were investigated.
Patients and Methods For adult inpatients in our hospital and related hospitals between 1984-2002, CNS syndromes with IM symptoms were examined, and serologic positives were assessed according to established criteria. Polymerase chain reaction (PCR) was performed for cerebrospinal fluid (CSF) from seven patients.
Results Ten patients with EBV-related CNS infections were found; their mean age was 36 years (20-79 years). The neurologic forms were as follows: acute encephalitis (4 patients), acute cerebellar ataxia (1), acute disseminated encephalomyelitis (ADEM) (2), myelitis (1), and meningitis (2). The PCR from CSF was positive in two patients with meningitis, one patient with ADEM, and one patient with encephalitis-associated chronic EVB infection. One case of encephalitis and another of relapsing ADEM were attributed to chronic EBV infection.
Conclusion Our study identified a variety of EBV related CNS infections. EBV CNS infections are divided into two groups: 1) CNS syndromes associated with primary EBV or reactivated infection, and 2) those associated with chronic EBV infection; it is notable that in the former, diverse CNS syndromes including ADEM can occur, whereas in the latter, chronic or recurrent CNS syndromes are produced.
(Internal Medicine 42: 33-40, 2003)

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Objective To investigate whether praziquantel is effective against diphyllobothriasis nihonkaiense at doses less than the conventional dose.
Patients and Methods Fourteen Japanese men with diphyllobopthriasis nihonkaiense were treated with a single administration of praziquantel at 5-10 mg/kg.
Results Twelve patients expelled a complete integrated Diphyllobothrium nihonkaiense with its scolex. One patient expelled an integrated D. nihonkaiense without its scolex, and one patient expelled 2 complete integrated D. nihonkaiense with their scolex, and an integrated D. nihonkaiense without its scolex. The lack of eggs in stool samples was confirmed in these 2 patients after the end of therapy. All patients had not expelled proglottides after the end of therapy for more than 1 year. No side effects were identified in any of the patients.
Conclusion All patients were considered to be cured. Our results indicate that the oral administration of a single dose of praziquantel at 5-10 mg/kg is effective and safe against D. nihonkaiense infections.
(Internal Medicine 42: 41-43, 2003)

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Limy bile is a rare condition characterized by excessive precipitation of calcium carbonate in the gallbladder. Cases of complicated hyperparathyroidism are extremely rare. There is only one reported case, where serum and urine calcium levels were high. On the other hand, the presence of limy bile in the common bile duct is also very rare, and has been reported in only 20 cases. We report a patient with obstructive jaundice in whom the initial abdominal radiography showed limy bile in the gallbladder and commonbile duct, and laboratory values showed a high serum calcium level and highly sensitive PTH (HS-PTH) level.
(Internal Medicine 42: 44-47, 2003)

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A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serumanti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.
(Internal Medicine 42: 48-52, 2003)

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Wedescribe a patient with acute myocardial infarction who showed ruptured plaque distant from the maximally stenotic lesion. In a 54-year-old male patient with acute antero-lateral myocardial infarction, coronary angiography showed a resolution of occlusive lesion with residual stenotic lesion in the middle portion of the left anterior descending artery (LAD) following t-PA administration. One month later, coronary angiography again disclosed significant stenosis of the middle LAD. Intravascular ultrasound revealed ruptured plaque that was located proximal to the maximally stenotic site which is generally considered as the culprit lesion. In this case, transient vessel occlusion occurred at the maximally stenotic site probably associated with plaque rupture distant from this lesion.
(Internal medicine 42: 53-55, 2003)

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We present herein a case of superior vena cava (SVC) syndrome caused by localized fibrosing mediastinitis (FM), which had histological features similar to xanthogranulomatous pyelonephritis (XGP). A 63-year-old womanpresented with facial swelling 5 months after undergoing right nephrectomy for XGP. Radiologic investigations of the chest confirmed the presence of SVC obstruction due to an intraluminal tumor. The histological features of the tumor were consistent with those of FM and were very similar to those of XGP. Although the pathogenesis of neither FM nor XGP is known, some pathogenic process of FM and XGP may be the same.
(Internal Medicine 42: 56-59, 2003)

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A 30-year-old man was admitted to our hospital for left lobar pneumonia with septic shock. Acute left-sided heart failure became evident as sepsis developed. Echocardiography revealed diffuse severe hypokinesis of the left ventricle (LV) and a pulmonary artery catheter showed Forrester subset II hemodynamics. Along with amelioration of sepsis and decrease of the serum concentrations of tumor necrosis factor-α and interleukin-6, LV hypokinesis improved. It is suggested that the patient's heart failure may have been due to functional depression of myocardial contractility resulting from a direct effect of the cytokines towards the cardiomyocytes, the so-called "septic myocardial depression".
(Internal Medicine 42: 60-65, 2003)

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We report a case of adrenal pseudocyst difficult to differentiate from pheochromocytoma. A right adrenal mass was found in a 41-year-old man after a traffic accident. Plasma level of renin was low, plasma level of aldosterone, and urine levels of aldosterone and catecholamines were high. Dynamic tests for primary aldosteronism and pheochromocytoma were negative. Noabnormal uptake was shown in ¹³¹I-adosterol or ¹³¹I-MIBG scintigram. Adrenal venous sampling presented high levels of catecholamines. Laparoscopic adrenalectomy was performed. Histological examination revealed a pseudocyst with a thick fibrocollagenous wall. Wediscuss the mechanism of high catecholamine levels in the right adrenal vein.
(Internal Medicine 42: 66-71, 2003)

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Primary AL amyloidosis involves vital organs from the early phase of illness, resulting in a poor prognosis. We report a patient with nephrotic syndrome due to this type of amyloidosis, who was successfully treated with two courses of VAD (vincristine, doxorubicin and dexamethasone) and subsequent high-dose melphalan (140 mg/m²) with autologous stem cell support. Following the serial chemotherapy his proteinuria improved, and M protein became undetectable in both serum and urine. To avoid the progression of primary AL amyloidosis, intensive chemotherapy should be actively used when the general status and vital organ functions are well preserved.
(Internal Medicine 42: 72-77, 2003)

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A 66-year-old man with diabetes developed acute renal failure after ingestion of Amanita pseudoporphyria Hongo. Laboratory data showed acute nonoliguric renal failure. A renal biopsy showed acute tubular necrosis with glomerular minor abnormalities. He received hemodialysis treatment for 3 weeks and his renal function normalized 2 months after admission. Wediscuss the differences in acute renal failure caused by possible toxins of Amanita pseudoporphyria Hongo from that caused by other poisonous mushrooms.
(Internal Medicine 42: 78-81, 2003)

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Wereport the case of a 58-year-old woman who was considered to have died of cyclophosphamide (CPA)-induced late-onset lung disease. She underwent a right-sided mastectomy due to breast cancer at the age of 50 followed by daily administration of 50 mg CPA and 20 mg tamoxifen for 2 years. A refractory cough and dyspnea began at the age of 56. Chest radiographs revealed diffuse infiltrates and pleural thickening. Her vital capacity was markedly reduced. Corticosteroid therapy was ineffective. The disease rapidly progressed with occasional episodes of pneumothoraces to her death. Postmortem examination revealed pulmonary fibrosis with marked elastosis.
(Internal Medicine 42: 82-87, 2003)

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A 19-year-old womanpresented with acute onset of cough and dyspnea. She started smoking two weeks before the appearance of symptoms. On admission, arterial blood gas analysis on room air breathing revealed PaO₂ 55 Torr. Chest roentgenogram and high resolution computed tomogramsshowedlocalized fine nodular shadows at the right lower lung field. Bronchoalveolar lavage fluid revealed a high eosinophil count. Eosinophil infiltration was also observed in transbronchial lung biopsy specimens. The final diagnosis was acute eosinophilic pneumonia (AEP). Although few reports have demonstrated diffuse fine nodular shadows in AEP, localized fine nodular shadows on chest roentgenogram and CT may some-times be the sign of AEP especially in the early phase of the clinical course.
(Internal Medicine 42: 88-91, 2003)

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Wereport a case of genital sarcoidosis that presented characteristic features on MRI. A 25-year-old man sarcoidosis patient with ocular and lung lesions presented a painful mass in the left scrotum together with systemic symptoms of fever, appetite loss, headache, and stomachache during the tapering of steroids. The patient was hypercalcemic, and this was thought to be the cause of his systemic symptoms. MRI showed multiple nodules of bilateral testes and enlargement of bilateral epididymis; the patient was diagnosed with testicular and epididymal lesions of sarcoidosis. An increased steroid dosage improved his hypercalcemia and genital lesions.
(Internal Medicine 42: 92-97, 2003)

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The association of malignancy with nephrotic syndrome and renal histopathologic abnormalities is well documented. We report a case of intravascular lymphomatosis (IVL) presenting as nephrotic syndrome which was diagnosed by renal biopsy. Histological examination of the renal biopsy specimens showed dissemination of neoplastic lymphoid cells throughout the glomerular capillary bed. These tumor cells were positive for CD20. Since the nephrotic syndrome improved with treatment of the lymphoma, intravascular lymphomatosis may well have played an important role in the pathogenesis of minimal change nephrotic syndrome in this patient.
(Internal Medicine 42: 98-101, 2003)

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A 53-year-old Japanese man with multiple sclerosis developed autoimmune neutropenia. The neutrophil count was consistently less than 0.2×10⁹/l, irrespective of the disease activity of multiple sclerosis or the administration of immunosuppressive agents or granulocyte colony-stimulating factor. After high-dose γ-globulin therapy was started, temporary increases in the neutrophil count were observed. Despite a wide spectrum of clinical manifestations in multiple sclerosis, autoimmune neutropenia has never been reported previously.
(Internal Medicine 42: 102-104, 2003)

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A 57-year-old man was admitted with fever and epigastralgia, and presented with splenomegaly and pancytopenia. A CT scan revealed splenic infarctions. There were no lymphadenopathies, skin lesions, or neurological abnormalities. A splenectomy was performed. Bone marrow involvement with hemophagocytosis was noted. The diagnosis of Asian variant of intravascular diffuse large B-cell lymphoma was based on intravascular and sinusoidal distribution of large CD5+ B cells. The patient died of the disease 11 months after onset. To our knowledge, this is the first report of AIVL that presented with splenic infarction. This distinct lymphoma should be included in the differential diagnosis of splenic infarction.
(Internal Medicine 42: 105-109, 2003)

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A 39-year-old man with no significant medical history was admitted to our hospital with severe abdominal pain and melena. Computed tomographic (CT) scans demonstrated superior mesenteric venous thrombosis. Although thrombolysis and anticoagulant therapy was started immediately, symptoms of strangulation ileus developed. Laparotomy was therefore performed and revealed necrotic stenosis of the ileum. The patient, his father and sisters showed low protein C levels. Direct sequencing analysis of their protein C gene revealed a heterozygous mutation at codon 169 corresponding to the cleavage site of the activation peptide, which was referred to as protein C Tochigi.
(Internal Medicine 42: 110-116, 2003)

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An 82-year-old man without notable medical history was admitted to our hospital following subacute deterioration of apettite, disorientation and strange behavior. There was spasticity of the right extremities without weakness. LDH and serum soluble IL2 receptor antibody levels were elevated, and as well as the protein level and IgG levels in the cerebrospinal fluid. CT scanning of the brain revealed a lesion at the left corona radiata. The patient's level of consciousness was worsening, and follow-up study of the brain showed a new lesion in the left occipital lobe. Intravascular lymphomatosis was therefore suspected. We performed a skin biopsy from two typical senile angiomas. In one of these biopsy specimens, a capillary hemangioma was present in the mid-reticular dermis and it was filled with abnormal B cells. The diagnosis of intravascular B cell lymphoma (IVL) was thus established. IVL is a rare subtype of extranodal diffuse large B cell lymphoma with a poor outcome. However, it is recently thought that if the diagnosis is established early, aggressive chemotherapy increases survival. Senile angioma is a skin eruption that is considered prevalent for the most part in elderly people. If a patient is suspected to have IVL, and there is no appropriate site of biopsy, it might be beneficial to try a skin biopsy aiming at senile angiomas for early diagnosis.
(Internal Medicine 42: 117-120, 2003)

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A 67-year-old woman suffered from symmetrical polyarthralgia and multiple joint swelling simulating rheumatoid arthritis (RA). Laboratory examination showed negative results for rheumatoid factor, decreased levels of IgG, IgA, and IgM, and an increased level of IgD. Immunoelectrophoresis in her serum and urine revealed an IgD-kappa monoclonal component and Bence Jones protein (kappa), respectively. A bone marrow biopsy showed an excess of atypical plasma cells. A synovial biopsy revealed amyloid deposition composed of IgD-kappa. She was diagnosed with amyloid arthropathy (AmyA) secondary to IgD-kappa multiple myeloma. It is important to pay attention to AmyA due to multiple myeloma in patients with seronegative RA.
(Internal Medicine 42: 121-124, 2003)

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