Characteristic bacterial species inhabit on or in the human body including the skin, mouth, pharynx, stomach, intestine, vagina, urethra, and make up indigenous bacterial flora. Equilibria exist not only between the indigenous flora and the host, but also between the different species within the flora. Many of indigenous bacteria are potential pathogens, while many non-pathogenic species have a similarly localized distribution. If the equilibra are disturbed by certain factors, the potential pathogens may become involved such socalled “opportunistic infections” as bacteremia, pneumonia, lung abscess, lung gangrene, peritonitis, cholecystitis, cholangitis, liver abscess, diarrhea, enteritis, stomatitis, tonsillitis, brain abscess, meningitis, pyelitis, cystitis, vaginitis, puerperal feber, endocarditis, tympanitis, conjunctivitis, soft tissue abscess, etc. Disturbances of equiblila are seen in such factors as administration of antibacterial agents or steroid homons, surgical operations, stresses, diabetes, overwork, aging, etc. Moreover, the intestinal flora possess a variety of enzymes that perform the extremely varied types of metabolism in the intestine, and influence host's health and diseases, including nutrition, physiologic function, drug efficacy, carcinogenesis, aging as well as the host's immunological responses.

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The pathogenesis and immunologic significance of epithelioid cell granuloma in primary biliary cirrhosis (PBC) were examined histologically, immunohistochemically and molecular biologically. Epithelioid granulomas were found in 40.8% of PBC livers. They were particularly frequent in the vicinity of damaged interlobular bile ducts, and their occurrence was closely related to the degree of cholangitis and portal inflammation. Granulomas were positive for HLA-DR and CD1d, and were surrounded by osteopontin-positive mononuclear cells and S-100-positive cells showing morphologically dendritic cells. We detected and identified bacterial gene by molecular biological methods such as PCR detection of bacterial 16S rRNA. Partial bacterial gene was amplified by PCR from the DNA samples, and the amplicons were cloned and sequenced for the identification of bacterial species. Next, a Propionibacterium acnes (P. acnes)-specific PCR was also performed. In granuloma, portal tracts, and periportal parenchyma, a number of bacterial gene were detected and the majority of them originated from enterobacterial species. Among them, P. acnes was detected in 20 of 50 sequenced clones from granuloma of PBC. By the P. acnes-specific PCR, distinct PCR products were identified in epithelioid granuloma in all PBC cases. The pathogenesis of granuloma in PBC suggested to be associated with a various immune response and several possible roles of enterobacteria in the etiopathogenesis were raised.

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Sarcoidosis, a chronic granulomatous disease, usually affects young adults and is believed to be rare in the elderly. To clarify the clinical features in elderly patients with sarcoidosis, we reviewed the medical records of 56 patients with sarcoidosis including 41 biopsy-proven cases and 15 clinically-diagnosed cases. Elderly patients who are over 65 years old were 15 cases. In the elderly patients, a female predominance was noted, as well as more frequent respiratory and ocular symptoms. Chest X-ray demonstrated most patients irrespective of the age presented with hilar or mediastinal lymphadenopathy only (stage I) and hilar or mediastinal lymphadenopathy with pulmonary parenchymal diseases (stage II). We further evaluated hilar and mediastinal lymphadenopathy and parenchymal abnormalities with high-resolution computed tomography (HRCT). There were no differences in the size of hilar and mediastinal lymphadenopathy between the elderly and younger patients. In contrast, ground-glass opacities were significantly more frequent and consolidation tended to be more common in elderly patients than in younger patients. In conclusion, elderly patients with sarcoidosis tend to be female having more respiratory and ocular symptoms, and presented with ground-glass opacities and consolidation on HRCT.

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1. Peritoneoscopy and liver biopsy was performed to examine hepatic involvement of sarcoidosis that was frequently found even without hepatic dysfunction. By this procedure seven sarcoidosis patients showed multiple miliary nodules on spleen surface without hypersplenism. Follow up of outcome of these patients showed good prognosis.
2. Sarcoidosis patients with SOL on abdominal CT were found in the patients older fourty with CXR stage II and III, hepatic and other extrapulmonary involvement and also elevated ACE in high frequency. Splenic involvement of sarcoidosis appeared as multiple whitish plaques and also several cuboid tumorous nodules, 1-2cm in diameter, on laparoscopy, multiple hypoechoic areas on ultrasound examination and multiple SOL on abdominal CT and MRI. SQL on abdominal CT disappeared after steroid treatment but reappeared during follow up in one case. In one of two patients who received splenectomy to rule out malignant lymphoma, lung lesion appeared on CXR during follow up. Therefore careful long term follow up study is necessary.

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A 48-year-old man was hospitalized with bilateral hilar lymphadenopathy and bilateral, upper predominant reticulonodular infiltrates on chest X-ray. However he had no respiratory symptoms. Lpithelioid cell granulomas were demonstrated by transbronchial lung biopsy as well as by biopsy of a subcutaneous nodule in his right leg. A diagnosis of sarcoidosis was considered. Nevertheless he had an occupational history of handling an alloy that contained a low level of less than 3% beryllium, which could cause chronic beryllium disease (CBD). Based on the negative results of beryllium lymphocyte proliferative tests (BeLPTs) using both his peripheral blood and bronchoalveolar lavage fluid, this case was finally diagnosed with sarcoidosis with an occupational history of a low-level beryllium alloy. Given the fact that low-level beryllium alloys are easily available without any restrictions in Japan, physicians who make a diagnosis of sarcoidosis should confirm a history of exposure to beryllium, especially use of those alloys and then exclude the possibilities of CBD by performing BeLPTs if the exposure to beryllium is under consideration.

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A 63-year-old woman presented with polyarthralgia in her extremities in July 2000. In November, blurred vision occurred. Ophthalmological examinations revealed vitreous snow-ball opacity, retinal vasculitis and macular edema, leading to the diagnosis of uveitis. Based on her ocular findings, sarcoidosis was strongly suspected, and she was admitted to our hospital in December. At the time of hospitalization, she showed polyarthritis in both hands, fingers, shoulders, knees and ankles. Blood analysis showed markedly elevated levels of CRP (8.9mg/dl), ESR (89mm/hr) and γ-globulin (33.6%), but the level of ACE was normal (13.3IU/l). Serum lysozyme level was mildly increased (11.6μg/ml). Rheumatoid factor was not detected in serum. PPD skin test was negative. Chest X-ray and CT showed no lymphadenopathy or lung field abnormalities. However, bronchoalveolar lavage fluid (BALE) analysis revealed increased levels of total cell count (2.2×10⁷), lymphocyte percentage (34.4%) and CD4/8 ratio (8.79). Abnormal ⁶⁷Ga uptake was observed in the right knee joint. Through these findings, the diagnosis of sarcoidosis was made clinically. Following the administration of prednisolone (30mg/day), her polyarthralgia dissapeared, and both CRP and ESR declined to normal levels. Her ocular findings also improved gradually. Polyarthritis is known to be an infrequent initial manifestation of sarcoidosis; systemic survey including ocular and pulmonary examinations is important for distinguishing sarcoidosis from collagen diseases.

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Right recurrent laryngeal nerve palsy and uveitis developed in a 31-year-old woman, for which the diagnosis of sarcoidosis was made clinically. Uveitis subsequently exacerbated and taste abnormality as well as unpleasant sensation at the right eye and right oral angle and right facial palsy occurred. On admission, she showed bilateral iritis and eye ground angitis, and neurological examination revealed anisocoria, slow light reflex of the left eye, peripheral right side facial palsy, right hypogeusia of the tongue, and positive finding for Chaddock reflex on the right side. Serum ACE level was within the normal range (23.4U/l). Cerebrospinal fluid test showed a slight increase in cell numbers and protein level. Chest X-ray and CT disclosed bilateral hilar lymphadenopathy. Gallium scintigram showed an accumulation of the tracer in the superior mediastinum. FLAIR (Fluid attenuated inversion recovery) MRI of the head revealed a high-signaled region around the aqueduct of the cerebrum, which was enhanced by gadolinium. Based on these findings and the course of illness, the patient was diagnosed as having neurosarcoidosis. The symptoms were relieved by administration of prednisolone, and the enhancement by gadolinium around the aqueduct of the cerebrum disappeared.

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We report diagnostic usefulness of epipharyngeal examinations in sarcoidosis.
Case 1: A 68-year-old woman had sarcoidosis-suspected diffuse lung abnormalities, uveitis and thrombocytopenia but declined to undergo transbronchial lung biopsy. Then, we referred her to an ear-nose-throat (ENT) specialist who incidentally discovered a mass in her upper respiratory tract. The biopsy specimen of the lesion contained non-caseating epithelioid cell granulomas. After she was treated by beclomethasone inhalation for 10 months for her asthmatic symptoms, the epipharyngeal mass showed marked shrinkage.
Case 2: A 23-year-old man with BHL was referred to our hospital and underwent transbronchial biopsy resulting in negative findings. An ENT specialist found rough surface in part in his epipharyngeal mucosa, and a biopsy of the portion disclosed sarcoid granulomas. He was followed up without treatment and the surface looked almost normal 10 months later, .
These two patients had no significant symptoms suggesting any topical involvements in the epipharynx. Epipharyngeal examination is not so invasive that this procedure should be made more positively to bring about diagnostic benefit for the patients of suspected sarcoidosis.

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A 57-year-old Japanese man was admitted to Sapporo medical university hospital because of hypercalcemia and renal dysfunction. Laboratory data disclosed elevated levels of serum and urine calcium and serum 1, 25(OH)₂D₃. Radiological examinations showed bilateral hiliar lymphangiopathy and renal stones. Histopathological findings of the lung and mediastinal lymph nodes biopsy specimens showed non-caseating epithelioid cell granulomas. Histopathological findings of the renal biopsy specimens were sclerosing glomerulonephritis and deposits of calcium crystal in renal tubules. Renal dysfunction improved with corticosteroid therapy, in parallel with decrease in serum 1, 25(OH)₂D₃ and serum calcium level. We reviewed reports on sarcoidosis with renal involvement.

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A 76-year old man, who had been diagnosed as sarcoidosis for eye symptoms, was admitted to a local hospital with dyspnea and hypoxemia. His chest X-ray and CT revealed diffuse ground glass opacity. He was transferred to our hospital for further examination. His symptoms and chest X-ray findings improved rapidly without any treatment. Histological examination of transbronchial lung biopsy and his clinical features suggested hypersensitivity pneumonitis rather than sarcoidosis. After 6 months, he had a fever with nodular shadows in the right lower lung field on the chest X-ray. Thoracoscopic lung biopsy was done, and a diagnosis of lung sarcoidosis was confirmed. This was an extremely rare case of sarcoidosis, which was clinically difficult to distinguish from hypersensitivity pneumonitis.

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To explore the relationship between sarcoidosis and tuberculosis, we studied patients from 15 national hospitals about the number of inpatients suffering from bacilli-positive tuberculosis, sarcoidosis, and both, and about the clinical features of the patients with both diseases during 10 years period (1989-1998). There were 11, 171 bacilli-positive tuberculosis patients, 224 sarcoidosis patients, and six patients with both diseases. The six patients (4 female and 2 males) aged from 56 to 75. Sarcoldosls preceded in four patients two of whom had already been treated with steroids. As to the stage of sarcoidosis, there were 3 patients in Stage I, one in Stage II, and 2 in Stage III. As to the type of tuberculosis, there were 3 patients in pulmonary tuberculosis, 2 in lymphnodal tuberculosis, and one in miliary tuberculosis.
The incidence of sarcoidosis in bacilli-positive tuberculosis patients was significantly high (53.7 per 100, 000 versus 5.1 per 100, 000 in the general population) in this survey. These findings support the view that there is some relationship between tuberculosis and sarcoidosis.

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The patient was 77-year-male who was diagnosed sarcoidosis of the skin by positive skin biopsy. Then Liver dysfunction and splenomegaly were pointed out, so he was diagnosed sarcoidosis of the liver by positive liver biopsy. After 23 months during prednisolone treatment toward sarcoidosis of the liver with portal hypertension, he complained of progressive dyspnea. He was intubated because of acute respiratory distress syndrome. His laboratory data revealed decreasing peripheral blood lymphocyte count and serum immunogloblin G, and Pneumosistis carinii-PCR was positive. These data showed that he became compromised host due to the prednisolone treatment. He was rescued by sulfamethoxazole/trimethoprim intravenous drip with methylprednisolone sodium succinate pulse therapy. We must be careful to infectious diseases according to steroid treatment for severe sarcoidosis of the liver.

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