The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that is often associated with lung cancer which shares a common antigenic protein with the motor nerve terminal. The myasthenic weakness is caused by an antibody-induced reduction in the release of acetylcholine from the nerve terminal. This study was undertaken to determine the target of LEMS antibodies and specify the voltage-gated calcium channel (VGCC) through which calcium influxes following the presynaptic membrane depolarization. Among the 5 types of VGCC, we found that the P/Q-type was highly recognized by LEMS antibodies. Using synthetic peptides or recombinant proteins as antigens for testing LEMS patients' sera or inducing an animal model of LEMS, we specified the S5-S6 linker regions in 3 of 4 domains constituting the α₁, subunit of P/Qtype VGCC as immunodominant sites. Synaptotagmin, one of the functionally VGCC-associated proteins and a protein functioning as a calcium sensor for exocytosis of synaptic vesicles, was also found to be a pathogenic immunogen of LEMS when the recombinant protein for antibody assay and the synthetic peptide for the induction of animal model were used as antigens. The present study forms a united front against cancer and cancer-related myasthenic syndrome.
(Internal Medicine 38: 86-96, 1999)

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Reactive arthritis is a member of the spondyloarthropathy. Bacteria which cause reactive arthritis infect the mucosal surfaces. Either the whole bacteria or their fragments are subsequently carried to the joints inside which are induced a TH1 lymphocyte response in which oligoclonal T lymphocytes as well peptide-specific CD8+ T lymphocytes participate. Human lymphocyte antigen (HLA)-B27 is a predisposing gene. Besides being determinants for the CD8+ T lymphocyte response it can also modify the response of other cells to the invasive bacteria. This would lead to alteration of the fate of the bacteria as well as release of arthritis-causing cytokines.
(Internal Medicine 38: 97-101, 1999)

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Eighteen patients with active Crohn's disease were treated with one leukocytapheresis session per week for a five-week intensive therapy, decreasing to one leukocytapheresis session per month for five sessions of initial maintenance therapy. Nutritional indices, inflammatory reactions, flow cytometry profiles, and cytokine production were also assessed before and after the intensive and initial maintenance therapy. Nine of the patients (50%) attained remission at the end of the intensive therapy. The nine non-remission patients had exhibited longer periods of suffering and more severely affected sites prior to the therapy. In 14 of 18 patients (77.8%), the nutritional indices, Internal Organization of Inflammatory Bowel Disease (IOIBD) score and Crohn's Disease Activity Index (CDAI) improved from the pretherapy levels, but only the remission group (50%) showed improvement in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The remission group showed significantly higher pretherapy CD4⁺CD45⁺ cell ratios and interleukin-2 (IL-2) production than the non-remission group, and significantly lower activated cells.
(Internal Medicine 38: 102-111, 1999)

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We studied the histories of eight patients who lacked clear evidence of cardiac abnormalities other than marked bilateral atrial dilatation and atrial fibrillation, which have rarely been discussed in the literature. From the time of their first visit to our hospital, the patients' chest radiographs and electrocardiograms showed markedly enlarged cardiac silhouettes and atrial fibrillation, respectively. Each patient's echocardiogram showed a marked bilateral atrial dilatation with almost normal wall motion of both ventricles. In one patient, inflammatory change was demonstrated by cardiac catheterization and endomyocardial biopsy from the right ventricle. Seven of our eight cases were elderly women. Over a long period after the diagnosis of cardiomegaly or arrhythmia, diuretics or digitalis offered good results in the treatment of edema and congestion in these patients. In view of the clinical courses included in the present study, we conclude that this disorder has a good prognosis.
(Internal Medicine 38: 112-118, 1999)

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In twelve patients with severe emphysema who underwent lung volume reduction surgery (LVRS), we assessed the results of dyspnea scale, pulmonary function, 6-minute walk distance (6MD), and thoracic movement prior to and 6 months following LVRS. Postoperatively, forced expiratory volume (FEV₁), maximum inspiratory mouth pressures (MIP), maximum expiratory mouth pressures (MEP), maximum voluntary ventilation (MVV), diffusing capacity for carbon monoxide (DLco), partial pressure of oxygen (PaO2) and 6MD were significantly increased with the decrease in dyspnea scale and lung hyperinflation. Thoracic movement, as assessed by the bilateral lung area ratio of the mid-sagittal dimension of dynamic magnetic resonance imaging (MRI) at full inspiration to that at full expiration, was significantly increased. The improvement in thoracic movement was significantly correlated with the increases in FEV₁, MVV, and MIP, and with the decrease in residual volume (RV), and with the improvement in the dyspnea scale. These findings suggest that LVRS is an effective procedure for improving not only the airflow limitation and gas exchange but also the thoracic movement in severe emphysema, and these improvements may contribute to an increase in exercise performance and relief of dyspnea.
(Internal Medicine 38: 119-125, 1999)

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We investigated the immediate effect of respiratory muscle stretch gymnastics (RMSG) and diaphragmatic breathing (DB) on the respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). Sixteen patients with COPD (age, 71.3 ± 3.9 year) were entered in the study. DB was performed for 10 minutes in supine position. For RMSG, 5 patterns were repeated 10 times each. Respiratory variables were measured in sitting position before and after both RMSG and DB, performed in random order, patient to patient, with a 20-minute washout period in-between. After RMSG, but not after DB, there was a significant overall prolongation in expiratory time. After DB, but not after RMSG, there was an overall decrease in minute ventilation, carbon dioxide output, respiratory gas exchange ratio, end tidal O₂ fraction, end tidal CO₂ fraction and tidal diaphragmatic volume. The results suggest that RMSG may have a beneficial effect on the respiratory pattern. On the other hand, DB may provoke post-hyperventilation hypoxemia.
(Internal Medicine 38: 126-132, 1999)

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We determined the cerebrospinal fluid (CSF) levels of adenosine, a mediator of cerebral blood flow regulation, and neopterin, a macrophage-producing compound, in patients with neurological disorders. Compared to control subjects, the adenosine levels were significantly increased in the patients with acute-stage cerebral infarction (n=12, p<0.0001), acute meningitis (n=10, p<0.0001), or amyotrophic lateral sclerosis (ALS, n=12, p<0.05) (Mann-Whitney U-test). The neopterin levels were significantly increased in the 41 patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP, p<0.0001), acute meningitis (p<0.0001), ALS (p<0.05) (Mann-Whitney U-test), or acute-stage cerebral infarction (p<0.005, Student's t-test). In the analysis of 41 HAM/TSP patients, the neopterin levels were significantly correlated with the cell number and glucose levels in the CSF, and were a sensitive marker of inflammation. Several of the HAM/TSP patients with increased adenosine levels were probably complicated with other diseases. The increased neopterin levels in the HAM/TSP group persisted, suggesting that the mononuclear cellular infiltration remained for a long time.
(Internal Medicine 38: 133-139, 1989)

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A 52-year-old Japanese woman was evaluated for severe hypertriglyceridemia and recurrent acute pancreatitis. This hypertriglyceridemia was found to be due to the absence of serum apolipoprotein C-II (apo C-II) which was identified by Western blotting using polyclonal anti-apo C-II antiserum. DNA sequence analysis of the apo C-II gene from the patient revealed a homozygous nucleotide change: a thymidine (T) to cytosine (C) substitution in codon 26 (TGG>CGG) at the third exon of the apo C-II gene, that resulted in a Trp²⁶ to Arg substitution. The mutation was also confirmed by restriction fragment length polymorphism (RFLP) analysis with the restriction enzyme Hpa II. The same mutation has been found in a case previously reported in Japan, and was named apo C-II Wakayama. However, the case in Wakayama prefecture showed two concomitant point mutations at the S'-flanking region upstream from the first exon, which were not identified in our case by RFLP analysis with the restriction enzyme BstXI. Considering that the prefectures of these two cases, Nara and Wakayama, are next to each other, the mutation in our case may be a genetic forebear of apo C-II Wakayama. However, no familial relationship between the two cases has been documented.
(Internal Medicine 38: 140-144, 1999)

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A germline mutation either in exon 10 or 11 of the RET proto-oncogene is found in the majority of patients with multiple endocrine neoplasia type 2A (MEN 2A). A 41-year-old female patient was referred for further evaluation of incidentally discovered right adrenal tumor. She had bilateral adrenal pheochromocytomas and medullary thyroid carcinomas detected by endocrinological and radiological examination, and diagnosed as MEN 2A. Molecular genetic testing of the RET exons 10 and 11 exhibited the identical somatic missense mutation at codon 634 in both tumors but did not confirm germline mutations in the corresponding sites. Possible mechanisms for tumorigenesis in this patient are discussed.
(Internal Medicine 38: 145-149, 1999)

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The efficacy of all-trans retinoic acid (ATRA) in patients with acute promyeiocytic leukemia (APL) has been well documented. However, ATRA is not as effective against other types of acute myelogenous leukemia (AML) or myelodysplastic syndromes. We present a patient with AML (FAB: M2) associated with a t(2;17;4)(p13;q21;p16) chromosomal defect in which the 17q21 breakpoint was not within the retinoic acid receptor α locus which is typically rearranged in APL. This patient was successfully treated with ATRA and granulocyte colony-stimulating factor and improvement of hematological parameters lasted for 19 months without the use of cytotoxic agents.
(Internal Medicine 38: 150-154, 1999)

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We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.
(Internal Medicine 38: 155-159, 1999)

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A 48-year-old woman was admitted to our hospital with high fever, chills, cough, and exertional dyspnea. On admission, the chest roentgenogram and computed tomography scan showed bilateral alveolar infiltration in the middle and lower lung fields. Microscopic examination of the bronchial lavage fluid showed flower cells typical for adult T-cell leukemia (ATL) and cysts of Pneumocystis carinii, and Legionella pneumophila serogroup 1 grew on buffered charcoal yeast extract (BCYE)-α agar. The patient was successfully treated with antibiotics including trimethoprim/sulfamethoxazole, erythromycin, and sparfloxacin. Remission of ATL was achieved after three courses of antileukemic chemotherapy. Mixed infection of opportunistic pathogens should be considered in patients with ATL.
(Internal Medicine 38: 160-163, 1999)

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