Mouse embryonic stem (ES) cells are the cells that possess pluripotential differentiation activity into not only all somatic cells but also germ cells. Genetic alteration of mouse ES cells can be easily achieved and such genetic modification can be introduced into the animal, since ES cells are differentiated into germ cells in vivo. This technology enables us to analyze the function of any particular genes of interest in mice. And in vitro differentiation induction of mouse ES cells into various cell lineages, such as blood cells, neural cells, and cardiac muscle cells, has been studied. In vitro hematopoietic differentiation experiments were carried out most extensively and can be regarded as a model system of induction. Recently, human ES cells have been established. Many scientists, clinicians and even mass media have entertained the idea that human ES cells can be used after changing the cells into lineage-specific stem cells or progenitor cells such as hematopoietic stem cells and neural progenitor cells.
(Internal Medicine 40: 195-200, 2001)

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Objective Soluble HLA class I antigens (sHLAs) in human serum have been reported to be associated with allografts and autoimmune disease and could modify immunological reactions induced by membrane type HLAs. To investigate the clinical significance of sHLAs in sarcoidosis, we assessed concentrations of sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined their production by peripheral blood mononuclear cells (PBMCs) and BALF cells.
Methods Concentrations of sHLAs were determined by enzyme-linked immunosorbent assay, using a monoclonal antibody against HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human β2-microglobulin. PBMCs and BALF cells were cultured in the presence or absence of either LPS or PHA.
Patients Serum levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy control subjects. sHLAs concentrations in BALF were also investigated in 17 active sarcoidosis patients and in 13 control subjects.
Results sHLAs levels in both serum and BALF were higher in sarcoidosis cases than in control subjects (p<0.05, in both). In the patients, values were significantly higher in active than in inactive stages (p<0.001) and significantly correlated with angiotensin-converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced amounts of sHLAs in patients with active sarcoidosis compared with those in control subjects.
Conclusion These results demonstrated that the level of sHLAs in serum is a useful index of disease activity of sarcoidosis, partly reflecting production by PBMCs and BALF cells.
(Internal Medicine 40: 201-207, 2001)

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Objective Chlamydia pneumoniae (C. pneumoniae) is an important pathogen for infections of the respiratory tract, and there are recently also a number of reports suggesting its relation with atherosclerosis. This study was performed to clarify the relation between C. pneumoniae infection and sclerotic lesions of the common carotid arteries.
Methods and Patients We evaluated sclerotic lesions of common carotid arteries by ultrasonography in 147 in-patients (mean age, 70 years; 95% confidence interval, 68-72) in the internal medicine ward, and studied the relation of the known risk factors for atherosclerosis including C. pneumoniae infection. An ultrasonograph and 7.5 MHz linear type B-mode probe were used by a specialist to evaluate sclerotic lesions of common carotid arteries. C. pneumoniae infection was determined by measuring anti-C. pneumoniae IgG specific antibody level (IgG index) using enzyme-linked immunosorbent assay (ELISA) method with serum of fasting blood, which had been preserved at -70°C.
Results IgG index (p=0.0263), from multiple regression analysis using various risk factors as explanatory variables, was a significant independent contributing factor (R2=0.3465, p<0.0001) along with known risk factors such as male (p=0.0289), age (p=0.0007), Brinkman index (p=0.0067), hypertension (p=0.0443) and T-Chol (p=0.0220).
Conclusion This study confirmed that the observations of an association between antibody against C. pneumoniae and common carotid atherosclerosis in Western nations is also present in Japan. Our results suggests that C. pneumoniae infection is also an important risk factor for common carotid atherosclerosis.
(Internal Medicine 40: 208-213, 2001)

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Objectives (1) To investigate the efficacy of infection control measures against methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in geriatric wards. (2) To identify predisposing risk factors for MRSA bacteremia.
Methods Cases with nosocomial bacteremias were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods and the period 1, January to December 1991, was applied as the control.
Materials We investigated patients with nosocomial bacteremias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University.
Results A significant reduction in cases with MRSA-induced nosocomial bacteremia was observed after the introduction of a stringent infection control and prevention program (period 1 vs. periods 2, 3, and 4: p<0.00833, p<0.00167, and p<0.00167, respectively). The major source of bacteremia included urinary tract infections, intravenous catheter-related infections, and infected decubitus ulcers. Improvement of decubitus ulcer was associated with a significant reduction in MRSA bacteremia (period 1 vs. periods 2 and 3: p<0.00017 and p<0.00833).
Conclusion Stringent infection control programs, including prevention and treatment of decubitus ulcers, are necessary in geriatric wards to reduce and prevent MRSA bacteremia.
(Internal Medicine 40: 214-220, 2001)

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Objective To describe the incidence of complications before and during therapy of Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS).
Methods A retrospective review of the patient's medical records.
Patients A total of 29 patients with AIDS and PCP who were admitted to the AIDS Clinical Center, International Medical Center of Japan from July 1996 to November 1999.
Results Adverse effects were found in 24 (88.9 %) of 27 patients treated with trimethoprim/sulfamethoxazole (T/S), 6 (46.1%) of 13 treated with parenteral pentamidine, and 2 (20%) of 10 treated with inhaled pentamidine. Infectious and/or non-infectious complications were found in 25 (86.2%) of 29 study patients. Regarding infectious complications, 16 (55.2%) were found on admission and 10 cases (34.5%) with infectious complications were identified during admission; including oral candidiasis (37.9% and 17.2%, respectively) and genital herpes (3.4% and 6.9%, respectively). Cytomegalovirus antigenemia was detected in 4 cases (13.8%) on admission and 12 cases (41.4%) during admission. Non-infectious complications affected 11 cases (37.9%) on admission, and 6 cases (20.7%) during admission, the latter included heart failure (10.3%) and pneumothorax (6.9%). PCP was successfully treated in all but one patient who suffered from repeated pneumothorax.
Conclusion Treatment of PCP can be problematic and it is important to be aware of the high incidence of various complications that can occur during the treatment of PCP.
(Internal Medicine 40: 221-226, 2001)

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In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.
(Internal Medicine 40: 227-231, 2001)

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Cardiac rupture is a fatal complication in the acute stage of myocardial infarction (MI). However, no measures have yet been established to predict it. Herein we describe three MI patients with cardiac rupture in whom plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations had been serially monitored from the onset of MI to cardiac rupture. In these cases, plasma BNP levels increased without symptomatic and hemodynamic changes and reached their highest level immediately before cardiac rupture, while plasma ANP levels remained unchanged. These cases suggest that the increased plasma BNP concentrations without symptomatic and hemodynamic changes may be a useful marker for predicting cardiac rupture after acute MI.
(Internal Medicine 40: 232-236, 2001)

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A 50-year-old woman treated for breast cancer with mitomycin C developed severe hypertension, followed by deep coma 3 days later. Computed tomography of the brain showed frontoparietal intracranial hemorrhage accompanied by subarachnoid hemorrhage. The patient was diagnosed additionally with hemolytic uremic syndrome (HUS) based on hemolytic anemia with schistocytosis, thrombocytopenia, and acute renal failure. The patient underwent hemodialysis and plasmapheresis with no improvement. We present the pathologic findings of the general vessels, which has been reported rarely. This case represents the first reported intracranial hemorrhage in HUS following mitomycin C administration. We emphasize the need to control blood pressure in patients with HUS.
(Internal Medicine 40: 237-240, 2001)

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Three cases of sarcoidosis with granulomatous interstitial nephritis are reported. Patients were all male and over 50 years of age. They simultaneously had evidence of multiorgan involvement of sarcoidosis including lung and skin and/or eye. In addition, distinct features were found in each case: a granulomatous infiltration mimicking unilateral renal tumor (case 1); renal insufficiency solely due to granulomatous interstitial nephritis (case 2); and renal insufficiency with calcemic nephropathy and granulomatous interstitial nephritis (case 3). Prednisolone therapy resulted in disappearance of the pseudotumor in case 1 and partial improvement of renal function in cases 2 and 3. In cases 2 and 3, however, plasma creatinine did not return to normal values and a second renal biopsy in case 2 demonstrated residual interstitial fibrosis and few granulomas, suggesting that steroid therapy did not achieve complete reversal of changes.
(Internal Medicine 40: 241-245, 2001)

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A 69-year-old woman with idiopathic thrombocytopenic purpura, who was regularly followed and treated with prednisolone and danazol, was admitted to our hospital because of shortness of breath. Chest roentgenogram showed a large amount of left-sided pleura! effusion. Gram-positive branching rods, subsequently identified as Nocardia farcinica, were isolated from the fluid. Antibiotic treatment together with pleural drainage with an intercostal catheter resulted in complete remission of pyothorax. Pulmonary nocardiosis is a rare disease, but recognition of the disease in immunocompromised patients and the prompt initiation of appropriate treatments based on isolation of the pathogen can lead to a successful outcome.
(Internal Medicine 40: 246-249, 2001)

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We report a female patient with left atrial wall invasion from pulmonary aspergillosis. She had been treated for diabetes mellitus. Pulmonary aspergillosis extended to the left atrial wall via the left pulmonary vein and formed a polypoid lesion in the left atrium. The polypoid lesion was composed of thrombus, and the thrombus increased in size to become large, and it showed invagination into the mitral valve during diastole. We considered that the thrombus was formed on the injured endocardium. Severe invasive aspergillosis thus could occur in a mild systemic immunocompromised host.
(Internal Medicine 40: 250-254, 2001)

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We report a 48-year-old woman who developed convulsive seizures and cerebral atrophy after recovery from fulminant hepatitis B with coma and cerebral edema at the acute stage. Neurological disturbances and cerebral signs are rare sequelae of fulminant hepatic failure (FHF); only a few cases have reported in the literature. Cortical laminar necrosis secondary to cerebral edema or delayed neuronal death due to toxic substances may have caused delayed brain atrophy and epileptogenesis.
(Internal Medicine 40: 255-258, 2001)

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Cerebral embolism in relation to cardiac amyloidosis has not been widely noted. A 47-year-old woman who had been suffering from familial amyloid polyneuropathy (FAP) for 7 years was treated with partial liver transplantation from a living donor and her early postoperative course was uneventful. During the 391st to 613th postoperative day she experienced recurrent cerebral infarctions, but clinical examinations revealed no disorders capable of producing cerebral embolism. At autopsy splenic infarction and intracardiac thrombi adhering to the mitral valve and left atrium were found, and these areas showed severe amyloid deposition. Amyloid heart is considered to be one possible cause of systemic embolism.
(Internal Medicine 40: 259-264, 2001)

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