Goro Asano

Study of the Mechanism Involved in Angiogenesis and Synovial Cell Proliferation in Human Synovial Tissues of Patients with Rheumatoid Arthritis Using SCID Mice

To examine whether synovial cell proliferation is due to angiogenesis, we studied the relationship between the inhibition of synovial cell proliferation and an angiogenesis inhibitor, TNP-470, in human synovial tissues. Human synovial tissues were implanted into the back of SCID mice (SCID-HuAg mice). Sixteen mice were divided into two groups of eight mice each: the untreated group (vehicle group) and the TNP-470-treated group that received a dose of 10 mg/kg body weight by subcutaneous injection. The number of blood vessels and synovial lining cells clearly increased in the vehicle group, but the number of synovial lining cells clearly decreased and the blood vessels were hardly detected in the TNP-470 group. Immunohistochemically, cells that stained positively for the anti–proliferating cell nuclear antigen (PCNA) mAb were abundant in synovial lining cells and endothelial cells in synovial tissues. Cells that stained positively for the anti-CD34 polyclonal antibody were abundant in the endothelial cells in the vehicle group, but these positively stained cells were hardly detected in the TNP-470 group. The PCNA positivity ratio in the vehicle group was 0.64 ± 0.019, whereas that in the TNP-470 group was 0.199 ± 0.007. The numbers of cells that stained positively for anti-CD34 polyclonal antibody were 242 ± 13.4 in the vehicle group and 153 ± 6.73 in the TNP-470 group per 10 microscopic fields. Cells that stained positively for anti-mouse CD31 mAb were mainly localized in the synovial lining, but invaded the subsynovial lining layer in human synovial tissues. On the other hand, cells that stained positively for anti-human CD31 mAb were mainly localized in the subsynovial lining layer. We found that endothelial cell proliferation is dependent on angiogenesis based on the result that angiogenesis and synovial cell proliferation were inhibited by treatment with TNP-470.

Mitochondrial function in canine experimental cardiac hypertrophy

Concentric left ventricular hypertrophy was produced in puppies by coarctation banding of the aorta at age 7 weeks. Hemodynamic, morphologic and biochemical studies were carried out 18 months after the operation. Systolic blood pressure proximal to the aortic constriction was 216 +/- 16 mmHg in experimental dogs compared with 115 +/- 5 mmHg in littermate control dogs. Ejection fraction of control and experimental dogs were 59 +/- 4 and 64 +/- 7, respectively. The left ventricular end-diastolic pressure was 6.0 +/- 0.4 in control and 8.4 +/- 1.1 in experimental dogs. There was no sign of overt heart failure in the experimental dogs. Anatomical analysis of different regions of the heart indicated that LV mass in the experimental dogs was increased by about 60%. Ultrastructure of mitochondria in situ, as observed under electron microscope, was normal both in control and hypertrophic hearts. Mitochondria isolated from epicardial and endocardial regions of the stable hypertrophic hearts showed normal rates of respiration, phosphorylation, citrate synthase, and cytochrome c oxidase activities compared to those isolated from hearts of littermate control dogs. It was, therefore, concluded that mitochondrial function is adequately preserved to meet the increased demand for energy in this model of stable cardiac hypertrophy of long duration.

Cytochemical studies on peroxisomes in rat and guinea pig myocardium

SummaryThe enzymatic activity and distribution of peroxisomes (microbodies) in rat and guinea pig hearts were studied cytochemically, by means of oxidation of 3-3′-diaminobenzidine (DAB) and by using B-glycerophosphate and cytidine-5′-monophosphate as substrates.Peroxisomes were localized in proximity to mitochondria and sarcoplasmic reticulum and measured from 0.2 μrn to 0.5 μm in diameter in both animal species. DAB positive bodies were seen both at pH 9.0 and pH 5.0 in rat myocardial cells. However, in guinea pig myocardial cells the reaction was observed only at pH 9.0, or very faintly at pH 5.0.Acid and alkaline phosphatases were not demonstrated in the peroxisomes. Lipid droplets were surrounded by a ring of dense granular reaction product for enzymes, such as acid and alkaline phosphatase, and lipofuscin granules were limited by acid phosphatase or DAB reaction products. The pathophysiological function of peroxisomes is discussed.

Buruli and the ulcers under the tropics.

Buruli ulcer, caused by Mycobacterium ulcerans is considered the third most prevalent mycobacteriosis after Tuberculosis and Leprosy. A largely neglected disease, it represents a serious treat to public health in poor and remote rural areas of endemic countries. Emerging since the eighties as an important cause of human suffering, the disease has been reported or suspected in more than 30 countries in the world. Although Africa remains the most affected region, Asia bears as well some endemic regions like Australia, India and Malaysia whether Buruli ulcer is an emerging or re-emerging remains subject of controversy. But, that Buruli ulcer is a neglected disease fits perfectly in the WHO definition of Neglected diseases. Although Buruli ulcer can prove extensively damaging to the skin, its awareness is very limited in the medical community as well as in the general public. This results in its underrecognition and thus its under-reporting. Its under-diagnosis or most frightening, its misdiagnosis can lead to life threatening consequences. We report here a series of 96 specimens of skin biopsy, obtained from the Agroyesum Catholic Mission Hospital in the Ashanti district of Ghana. Thirty % of the specimen in the series proved to be misdiagnosed lesions, other than Buruli ulcer. Among these, 1/3 were malignant lesions ranging from fibrosarcoma to malignant melanoma. The remaining were inflammatory tumorus conditions. The aim of the present study is to emphasize that Buruli ulcer can lead to confusion with the wide spectrum of tropical both parasitosis and infectious conditions that can mimic its different clinical presentation.

ハンセン病(LLs)に生じた脂漏性角化症の表皮内菌球についての検討

A 67-year-old patient has had exanthema in the lower right limb since 51 years ago (16 years old at onset), which underwent repeated remission and recurrence. At present, he has bilateral symmetrical widespread infiltrating exanthema and asymmetrical marked neuralhypertrophy, and has been diagnosed typical LLs (His father had the same disease). The exanthema recurred several years ago, and the patient is being treated for Hansens disease. He had a dark brown flat elevation with a rough surface and the size of a small finger tip in his right abdominal skin for approximately 20 years. A biopsy was performed, and the specimen was fixed in 10% formalin and paraffin sections were prepared for histopathologic examination. A part of the specimen was processed forscanning electron microscopic examination. Seborrheic keratosis was diagnosed by H & E staining. Acid-fast (FITE) staining, immunohistochemical staining (keratin, S-100 protein, anti-PGL antibody and anti-BCG antibody) and scanning electron microscopy revealed the presence of bacteria (M. leprae) in the dermal foam cells, the matrix with a banded structure and the squamous epithelial cells which normally lack phagocytosis function. Compared to the basal cells of normal epidermis, the basal cells located adjacent to the dermis affected with seborrheic keratosis showed increased proliferation and more marked characteristics of a germinative cell. The degree of differentiation of the basal cells appeared regressed, and they probably possessed augmented phagocytic activity. The phagocytosed bacteria were probably carried by the epidermal cell cycle toward the surface layer. However, bacteria could not be found in the stratum corneum, probably due to an association with the lysosome.

A case of renal cancer discovered by multiple skin transition.

A 74-year-old female with skin metastasis of renal cell carcinoma is described.She noticed her cutaneous lesion on her left lower abdomen about three years before visiting our dermatological outpatient clinic. The lesion gradually enlarged and multiple nodule developed on the other parts of the body.The biopsy was taken from the lesion on the right arm. On microscopic findings, the metastasis of renal cell carcinoma was suggested. An examination of whole body was performed and renal cell carcinoma of left kidney was discovered. Systemic and multi-organ involvement were also observed.This case is rare because the patient had a large number of metastatic skin lesions up to 62. In addition, she lived at least 3 years after the metastasis of the skin. It is relatively a long period for the patient with metastatic renal cell carcinoma.