Aida S, Takahashi Y, Suzuki E, Kimula Y, Ito Y, Miura T
Respiration 1992;59(4):201-210
Electron-microscopic evidence for cytochrome P-450 in Clara cells and type I　pneumocytes of the rat lung. Using immunoelectron microscopy, we examined the distribution of cytochrome P-450 in rat lungs and determined the cell types in which P-450 was localized.　To demonstrate P-450, a rabbit polyclonal antibody against P-450b (P-450 IIB1),　the major constitutive isozyme of rat pulmonary P-450, was used. Strong　reactivity for anti-P-450b antibody was observed in nonciliated bronchial and　bronchiolar epithelial cells (Clara cells) and type I pneumocytes. Type II　pneumocytes and Kultschitzky cells showed no reactivity. Most ciliated cells　were negative, although a small number in peripheral bronchioles showed a　weakly positive reaction. Endothelial cells and other mesenchymal cells were P-450b negative. Many studies have suggested that the Clara cell was metabolically very active and had P-450 containing mixed function oxidase　systems. Our study shows that both Clara cells and type I pneumocytes have　P-450 and may play an important role in the metabolism of xenobiotics. The　metabolic significance of type I pneumocytes was not recognized, but it is　reasonable to postulate that type I pneumocytes may have a xenobiotic metabolic　function because they comprise most of the surface area of the lungs and are　thus extensively exposed to the environment.

Amatya BM, Kimula Y, Koike M. The Clara cells activated by acetaminophen. J Med Dent Sci. 2002 Dec;49(4):103-8.
Many high mountaineers die of acute mountain sickness in the high mountains of Nepal during their adventure. Most of them administer acetaminophen (AP) as an analgesic. Various cells with higher expression of cytochrome P-450 (CYP) would metabolize AP and lead to cellular impairment. CYP is a major enzyme system in the metabolism of xenobiotics in different organs of the human being including in Clara cells of the lungs. Clara cells contain the highest concentration of CYP. We injected AP to C57BL/6J mice to examine the toxicity of AP in Clara cells. In 8 hours Clara cells show more prominent apical protrusion with edematous smooth endoplasmic reticulum (sER), reduced secretary granules, and edema. We speculate that using AP in a high mountain area might be harmful for Clara cells being a trigger of high altitude sickness.

Amatya BM, Kimula Y. Cysticercosis in Nepal: a histopathologic study of sixty-two cases. Am J Surg Pathol. 1999 Oct;23(10):1276-9.
Human cysticercosis, an infection caused by larvae of Taenia solium, is a major public health problem in many developing countries. Sixty-two of 23,402 biopsy cases have been detected as cysticercosis in the last 5 years in Patan Hospital. Most (82%) of the patients presented with solitary skin nodules, another 10% with nodules in the oral mucosa, and 8% in the breast. Forty cases were identified from the Kathmandu valley and the rest from outside Kathmandu. Most patients were younger than 30 years of age (mean, 21+/-11 years). Statistically, there was no difference between males (0.28%) and females (0.24%). The average size of cysticercosis was 19 mm in diameter, and the histology of cysticercosis showed fibrous walled cysts covered by several layered epithelioid cells with a few Langhans' giant cells and infiltration of eosinophils without caseous necrosis. These cysticercosis findings from an endemic area will be helpful for doctors who examine immigrant patients in nonendemic areas.

Aoshima M,  Kameyama S, Murai Y, Yokose T, Chiba K, Kimura Y, Ozawa A
[A case of follicular bronchiolitis with broncho-pleural fistula in rheumatoid arthritis]. Nippon Kyobu Shikkan Gakkai Zasshi 1991 Sep;29(9):1195-1201
A 67-year-old male diagnosed clinically as having rheumatoid pleuritis and bronchiolitis was treated with adrenocorticosteroid. His clinical findings improved, but following the tapering of the steroid dose, exacerbation occurred. After the steroid dose was increased, serological findings improved, but chest X-ray findings revealed no improvement. To re-evaluate the etiology of the bronchiolar lesion, open lung biopsy was performed. The biopsy specimen showed lymphocytic infiltration and formation of lymphoid follicles in and around the bronchioles. The pulmonary lesion was diagnosed as follicular bronchiolitis.

Aryal G, Kimula Y, Koike M.
Ultrastructure of Clara cells stimulated by isoproterenol. J Med Dent Sci. 2003 Sep;50(3):195-202.
The incidence of peripheral pulmonary adenocarcinoma has increased in recent years. Clara cell has been known as target for carcinogens and source of pulmonary tumors. One of the presumed roles of the bronchiolar Clara cell is the secretion of pulmonary surfactant into the bronchiolar lumen. To establish the secretory morphology of Clara cell, a well-defined secretory agonist, isoproterenol (500 mg/kg) and the antagonist, propranolol (20 mg/kg), were administered into five-week old mice. The secretory response was examined at 1 hour and 4 hours after injection. Ultrastructural morphometry was used to quantitate the secretory response by measuring area of apical cap of the Clara cells. Isoproterenol caused a significant increase in area of apical cap of Clara cells 1 and 4 hours after injection (p < 0.0001), while pretreatment with propranolol prevented this effect at 4 hours. Propranolol alone significantly decreased the area of Clara cells (p < 0.0001). Clara cells secretory granules disappeared 1 hour after propranolol plus isoproterenol administration, and the granules reappeared at 4 hours. The accelerated secretion of Clara cells by isoproterenol provides evidence of their secretory mechanism controlled by beta-adrenergic agonists. The study has confirmed the secretory role of Clara cells. The secretion is both apocrine and merocrine type.

Hiraoka N,  Odama S, Unoura K, Takano S, Taniai S, Shirai T, Kimura Y, Yoshizawa Y
Five cases of female pneumothorax with endometriosis on the blebs
Nihon Kokyuki Gakkai Zasshi. 2005 Jan;43(1):53-8
A part of catamenial pneumothorax is associated with endometriosis. Several cases were reported where CA125 levels were high in blood or pleural effusion. A case of female pneumothorax, the bleb and diaphragm showed positive for CA125, was reported. Additionally in the 5 cases of 6 female pneumothorax, the blebs showed positive for CA125, CD30, progesterone receptor and estrogen receptor. Endometriosis on the blebs was found in 4 of 6 cases by hematoxylin-eosin staining and in 5 of 6 cases by immunostaining. It is suggested that endometriosis on blebs is an origin of female pneumothorax.

Inase N, Takayama S, Nakayama M, Miura H, Kimula Y
Pulmonary clear cell carcinoma.
J Surg Oncol 1991 Oct;48(2):145-147
A case of pulmonary clear cell carcinoma is demonstrated. A large left lower lobe mass, without lymphadenopathy was detected on a screening chest X-ray, and a left lower lobectomy was performed. The tumor was composed predominantly of clear cells with some areas showing cells typical for small cell carcinoma. Ultrastructurally, the larger clear cell had cytoplasm containing many rough endoplasmic reticuli and free ribosomes, while the smaller dark cell showed a serrated nucleus and scanty cytoplasm having many free ribosomes without neurosecretory granules. This is the first report on pulmonary clear cell carcinoma with small cell carcinoma patterns, and this case will throw doubt on the conclusion of previous studies that clear cell carcinoma is not a separate entity.

Inase N, Takayama S, Nakayama M, Miura H, Kimula Y
Jpn J Med 1991 Jul;30(4):343-345
Pleural mesothelioma after neighborhood exposure to asbestos during childhood.
A 38-year-old woman with pleural mesothelioma who had a history of neighborhood asbestos exposure during her childhood was demonstrated. She had no known history of occupational asbestos exposure. This is the first case of mesothelioma with neighborhood asbestos exposure reported in Japan. Previously-reported cases of mesothelioma with neighborhood asbestos exposure in the English language literature were reviewed.

Inase N,  Usui Y, Tachi H, Takayama S, Nakayama M, Korenaga M, Miura H, Kimula Y
Sjogren's syndrome with bronchial gland involvement and multiple bullae.
Respiration 1990;57(4):286-288
A 52-year-old woman with Sjogren's syndrome presented with a dense lymphocytic infiltrate around the bronchial gland disclosed by a transbronchial lung biopsy specimen. Two and a half years after the initial evaluation, her pulmonary status had deteriorated and multiple bullae had developed at both lung bases.

Inoue T,  Kimula Y, Tanaka Y
Gamma heavy chain disease; report of an autopsy case with a review of the literatures.
Acta Pathol Jpn 1976 May;26(3):385-397
An autopsy report of a 76 years old Japanese male, who had suffered from gamma-HCD, was presented. This is the fifth case of gamma-HCD in Japan and this communication is the first autopsy report made on gamma-HCD in our country. The primary pathological alteration of this disorder is a neoplastic proliferation of atypical lympho-plasmacytes extending throughout the entire hematopoietic and parenchymatous organs. Pathological characteristics of our case were compared with the same disorders reported in the world literatures.

Inoue T,  Kimula Y, Tanaka Y, Shirakura T, Hayashi-Nakao J
Unusual primary malignant reticulosis of the bone marrow.
Acta Pathol Jpn 1978 May;28(3):491-505
An unusual case of primary reticulosis of the bone marrow in a 67-year-old female has been described. Pathological-anatomical characteristics of the present case are as follows; 1) Primary non-destructive proliferation of neoplastic reticulum cells or their variants, confined to the systemic bone marrow. Metastatic foci were noted in several areas where extramedullary hematopoiesis occurred. 2) Cytologically, neoplastic cells resemble atypical plasmacytic cells. No active phagocytosis was noted in neoplastic cells. 3) Histologically a significant increase in reticulin fibers was observed closely associated with proliferating cells. 4) Electron-microscopically these cells showed developed endoplasmic reticula but were distinguishable from myeloma cells by their irregular cytoplasmic border, which became frequently obscure, and by the presence of a desmosome-like structure. 5) These cells showed a negative immunofluorescent reaction to all types of human immunoglobulin classes. The morphological characteristics of these cells distinguished the disorder from poorly differentiated myelomatosis.

Jinn Y,  Ohkochi M, Takayama S, Miura H, Kimula Y, and Yoshizawa Y.
Primary extramedullary plasmacytoma of the lung with production of M-protein: a case report.
Japanese Journal of Lung Cancer 40(7):783-786,2000
We describe here a rere case of primary extramedullary plasmacytoma of the lung in an 86-year-old Japanese man. Immunohistochemical staining of biopsy specimens for IgG-kappa was positive, and serum immunoelectrophoresis showed monoclonal IgG-kappa. There was no evidence of the presence of multiple myeloma. Chemotherapy was given, but tumor size did not decrease significantly.

Kimula Y,

A histochemical and ultrastructural study of adenocarcinoma of the lung.
Am J Surg Pathol 1978 Sep;2(3):253-264
Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally.

Kimula Y,  Utsuyama M, Yoshimura M, Tomonaga M
Element analysis of Lewy and adrenal bodies in Parkinson's disease by electron probe microanalysis.
Acta Neuropathol (Berl) 1983;59(3):233-236
Two possible interpretations of the origin of Lewy bodies and adrenal bodies found in Parkinson's disease are now under discussion: a disorder of (1) catecholamine metabolism or (2) sphingomyelin lipidosis. From the electron probe microanalysis of Lewy bodies and adrenal bodies, we find that the Lewy body contains sulfur, calcium, and phosphorus, and the adrenal body also contains these three elements. Furthermore, a positive correlation was obtained between the X-ray intensity of the sulfur and the diameter of adrenal body. For Lewy bodies, this correlation was not obtained. The results suggest that a common mechanism may exist for the production of Lewy and adrenal bodies, although they differ somewhat in their accumulation of sulfur. It is considered that both structures may originate, in part, from degenerated protein containing sulfur.

Kitamura H,  Kitamura H, Tozawa T, Kimula Y
Cemented tungsten carbide pneumoconiosis.
Acta Pathol Jpn 1978 Nov;28(6):921-935
An autopsy case of cemented tungsten carbide pneumoconiosis, the first lethal case in our country, is presented. A 28-year-old woman, who had been engaged in grinding presintered metallic matrix for four years, developed respiratory symptoms. X-ray examinations were indicative of interstitial pulmonary fibrosis. Corticosteroid therapy revealed only little effect. She expired five years after the onset of the symptoms. Postmortem examination showed nonspecific interstitial pneumonitis resulting in marked lung fibrosis. Ultrastructurally, crystals were observed in cytoplasm of presumable macrophages in the fibrotic lung tissue. Electron probe microanalysis of the lung tissue showed the presence of tungsten and other constituents of tungsten carbide except for cobalt. Metal analysis demonstrated a large amount of tungsten in the lung. Cobalt was detected tenfold of the normal value in the bone. In pathogenesis of the pneumoconiosis in the cemented tungsten carbide workers, toxicity of cobalt is most suspectable, and in addition, individual susceptibility may be also important.

Kraus MD, Amatya BM, Kimula Y
Histopathology of typhoid enteritis: morphologic and immunophenotypic findings.
Mod Pathol 1999
Enteric fever is a systemic illness caused by Salmonella infection, with S.typhi, S. paratyphi, and S. enteritidis being the most common serotypes. Humans are the only reservoir for S. typhi, and its predilection for the ileum is due to the fact that organisms enter the body by translocation across specialized Peyer's patch epithelium and then proliferate in the mucosal macrophages. The lesions in bowel and mesenteric lymph nodes are distinctive and mimic Kikuchi-Fujimoto disease and Rosai-Dorfman disease as well as infections caused by some non-salmonella bacteria. The four cases presented in this report, two culture-confirmed, all exhibited ileal mucosal hypertrophy caused by a neutrophil-poor monocyte/macrophage-rich hyperplasia. Though diffuse areas were present, much of the lesional proliferation was nodular, representing macrophage infiltration and colonization by the monocytes and macrophages. Immunophenotypic studies, which showed a CD68+, lysozyme+, UCHL-1+, OPD4-, CD4-, s100- profile, were helpful in distinguishing these lesions from other processes, including Kikuchi-Fujimoto disease and Rosai-Dorfman disease. Although rare in developed countries, enteric fever should be considered in any patient with recent travel to endemic areas and in the context of illness thought to be related to contaminated foods.