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Biomedical subjects

F Otsuka

Publications and source records attributed to F Otsuka.

At least 19 recordsLinked to original sources

Characterization of the mouse CD8 beta chain-encoding gene promoter region.

We identified a regulatory region of the mouse CD8 beta chain-encoding gene (CD8b) promoter. The CD8b 5' upstream sequence could not drive the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene without T-cell receptor or SV40 enhancer elements. The results of transient transfection assays indicated that the dominant transcription-activating element within the CD8b-promoter is located at -45 to -40 base pairs (CCGCCC) from the transcriptional initiation site. Elimination of this element, by deletion or specific point mutation, significantly reduced transcriptional activity from this promoter. The sequence of this core region corresponds to a GC box motif known to act as a binding site for a ubiquitously expressed transcriptional activator, Sp1. However, the promoter activity appeared to be T-cell-specific, and the gel retardation assay using the core sequence as a probe revealed formation of complexes with multiple nuclear factors, one of them being specific to T lineage cells. These data suggest that the CD8b promoter requires a cis-acting element as well as several nuclear factors for full-range, tissue-specific transcription.

Animals

Effect of a chemically-synthesized acylglucosylceramide, epidermoside, on normal human keratinocyte differentiation.

Epidemosides (N-(0-linoleoyl)-(1)-hydroxy fatty acyl sphingosyl glucose) are found exclusively in the epidermis not in dermis, and are thought to play important role in forming the mammalian epidermal permeability barrier. A species of epidermoside isolated from guinea pig epidermis and named lipokeratinogenoside has been shown to enhance fetal rat keratinocyte differentiation. In the present investigation, we studied the effects of a chemically synthesized equivalent of human epidermoside on the viability and differentiation of cultured human keratinocytes (HK Cells). The chemically-synthesized epidermoside was not toxic to cultured HK Cells at concentrations of 0.01 to 10 micrograms/ml. When 10 micrograms/ml of the chemically-synthesized epidermoside was added to keratinocyte growth medium containing 1.2 mM Ca2+, HK Cells showed a 5.6-fold increase of keratin content compared to the vehicle treated control at 144 h of cultivation, and they also displayed morphological changes suggestive of differentiation. A similar increase of cellular keratin content was observed in HK cells treated with tetradecanoyl phorbol-13 myristyl-12 acetate (TPA), an agent known to enhance the differentiation of keratinocytes. Lipokeratinogenoside also increased the keratin content of cultured HK cells. These results suggest that epidermosides have an ability to enhance keratinocyte differentiation. Epidermoside could thus be a key molecule, not only as a constituent of the epidermal permeability barrier, but also as a regulator of keratinocyte differentiation.

Animals

Karyotyping by PFGE of clinical isolates of Sporothrix schenckii.

From October 1991 to December 1992 we had eight patients with sporotrichosis at Tsukuba University Hospital in Japan. With 8 strains isolated from these patients, PFGE (pulsed-field gel electrophoresis) analyses were carried out to examine whether the karyotype of S. schenckii is distinguished by our method and whether this molecular approach is a useful means of biotyping of S. schenckii strains. Chromosomes were separated by contour-clamped homogeneous electric field (CHEF) gel electrophoresis. The strains had six to eight chromosomes and a total genome size was approx. 28 Mbp. Although these karyotypes of all the isolates looked closely similar to each other, they were grouped into three types.

Electrophoresis, Gel, Pulsed-Field

Multiple malignant eccrine poroma and a linear epidermal nevus.

A 68-year-old woman developed three reddish nodules on a linear epidermal nevus on the right arm. The nodules and linear lesion were resected. The histology revealed the two larger nodules to be eccrine porocarcinoma and the other to be eccrine poroepithelioma. The linear lesion was actually epidermal nevus. To our knowledge, this is the first description of adnexal tumors developing on epidermal nevus.

Acrospiroma

Rheological analysis of peripheral blood neutrophils in a patient with cutaneous and arthropathic psoriasis accompanying hypopyon-iridocyclitis.

A 32 year old Japanese male has had several synchronized attacks of psoriatic arthritis and hypopyon-iridocyclitis. During exacerbations, he has a leucocytosis with neutrophilia and elevated C-reactive protein. Assessment for adhesiveness, aggregation and deformation of peripheral neutrophils revealed strikingly high rheological activity whereas during periods of remission the activity was only slightly elevated above normal.

Adult

Syndrome of inappropriate secretion of antidiuretic hormone following intra-thoracic cisplatin.

A case of malignant thymoma with pure red cell aplasia (PRCA) complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following intrathoracic cisdichlorodiammine platinum (CDDP) administration is reported. A 59-year-old Japanese woman who presented with severe general fatigue was diagnosed with PRCA associated with a thymoma, based on the findings of a bone marrow biopsy, computed tomography of the chest, and the existence of anti-acetylcholine receptor antibodies. She underwent a thymectomy after frequent blood transfusions. This was followed by intrathoracic CDDP administration, because of pleural dissemination. Nine days following chemotherapy, her serum sodium concentration was found to be 104mM, while her consciousness was drowsy with severe fatigue and vomiting. This hyponatremic state was diagnosed as SIADH induced by CDDP infusion into the thoracic space, based on the hypo-osmolality of her serum, the hyper-osmolality of her urine, and an inappropriate level of plasma vasopressin.

Cisplatin

Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus with antiphospholipid antibody.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity characterized by the formation of fibrous tissue plugs within terminal bronchioles and alveolar ducts. Although BOOP has been associated with several connective tissue disorders, there are rare reports of BOOP in patients with systemic lupus erythematosus (SLE). We present a patient with SLE accompanying antiphospholipid antibody who developed recurrent respiratory symptoms and radiographic abnormalities. The diagnosis of BOOP was confirmed by transbronchial lung biopsy. This case suggests that not only SLE, but also the presence of antiphospholipid antibody, may be associated with the development of BOOP.

Adult

Prognostic significance in malignant melanoma of nuclear DNA content measured by a microfluorimetric method.

The nuclear DNA content of 47 primary malignant melanomas was measured by 4',6-diamidino-2-phenylindole-DNA (DAPI-DNA) microfluorimetry, and the DNA index, a quantitative measure of nuclear DNA content, was calculated. The DNA index and other clinical and pathological variables were examined and compared with patient survival using univariate and multivariate analyses. The Kaplan-Meier life table method revealed that the DNA index and metastases to regional lymph nodes significantly correlated with patient survival. A Cox proportional hazards multivariate analysis demonstrated that the DNA index, which was not significantly correlated with other variables, was the most reliable and independent factor for predicting patient survival.

Adult

Immunohistochemical localization of keratins and involucrin in solar keratosis and Bowen's disease.

The present study was conducted to determine the patterns of immunohistochemical characterization of keratin (K) and involucrin in solar keratosis and Bowen's disease in order to clarify the abnormal differentiation or maturation of the tumor cells in these precancerous epithelial dermatoses. Seventeen human anti-cytokeratin antibodies and an anti-involucrin antibody were used to examine 15 cases of solar keratosis and 18 cases of Bowen's disease. Formalin-fixed and paraffin-embedded sections were stained with these antibodies by the avidin-biotin-peroxidase technique. In solar keratosis, keratin and involucrin distribution was similar to that in normal epidermis, whereas in Bowen's disease the keratin distribution varied among individual cases. The dyskeratotic cells in Bowen's disease showed a reduction or loss of staining with these antibodies, and they were occasionally positive for keratin 19. These observations suggest that there is a difference in keratin and involucrin expression between solar keratosis and Bowen's disease and that the atypical cells of Bowen's disease exhibit a diversity of differentiation.

Aged

Polysialogangliosides expressed by amelanotic melanoma: a possible explanation for the poor response to anti-monosialoganglioside antibody 202 in a patient with melanoma.

A 52-year-old Japanese woman developed numerous amelanotic metastatic melanomas on the skin and in various organs three years after a surgical operation for primary melanoma on the right axilla. The patient was treated with monosialoganglioside specific monoclonal antibody 202; however, no apparent clinical effects were observed. Ganglioside analysis of a metastatic tumor demonstrated that it expressed GM3, GM2, GD3, GD2, and polysialogangliosides. Since polysialogangliosides rarely appear in melanomas, their expression may explain the patient's poor response to MAb 202. The relationship between ganglioside composition and the effect of anti-ganglioside monoclonal antibody is discussed.

Antibodies, Monoclonal

Late onset systemic lupus erythematosus diagnosed in an elderly man with unusual skin eruptions and sudden death.

A rare case of late onset SLE in an elderly man presented with generalized toxicoderma-like eruptions. The rash first appeared at age 64 years and was characterized by dark or purplish erythematous eruptions disseminated over the body surface. Histological examination revealed marked liquefaction degeneration and leukocytoclastic vasculitis. Direct immunofluorescence study and serological examination results were suggestive of SLE; however, the patient had no episodes of photosensitivity, malar erythema, or arthralgia. He was diagnosed as having SLE 11 months after his first visit and died suddenly 16 months after onset. Elderly men with SLE can present with unusual clinical manifestations; careful examination of these patients is required to reach a correct diagnosis.

Age of Onset

Changes of cytokeratin and involucrin expression in squamous cell carcinomas of the skin during progression to malignancy.

The detection of cytokeratins in neoplastic tissues by immunohistochemical methods has numerous diagnostic and investigative applications, because cytokeratins are usually conserved in tumour cells during malignant transformation. Recently, however, it has been reported that progression to malignancy is associated with commencement of expression of low-molecular-weight cytokeratins. In the present study, 42 specimens from 35 cases of squamous cell carcinoma (SCC) of the skin were analysed by immunohistochemical techniques, using polyclonal anti-involucrin antibody and a panel of monoclonal antikeratin antibodies, in order to investigate the nature and differentiation of SCCs. The expression of cytokeratins and involucrin in well-differentiated SCCs was similar to that in normal epidermis. In contrast with well-differentiated SCCs, the expression of differentiation-specific cytokeratins and involucrin was diminished in the immature tumour cells in proportion to the malignancy of the SCCs. Some antibodies, however, stained all tumour cells, irrespective of the degree of malignancy. Furthermore, expression of simple epithelial and non-cornifying stratified squamous epithelial cytokeratins was observed in atypical tumour cells of poorly differentiated SCCs. It is of interest that similar expression was noted in many tumour cells in the lymph node metastases and in some tumour cells in the primary cutaneous lesions. Cytokeratin expression similar to that in normal epidermal keratinocytes was conserved in well-differentiated SCCs, but the expression of cytokeratins changed during progression to malignant transformation. The expression of simple epithelial or non-cornifying stratified squamous epithelial cytokeratins in cutaneous SCCs may be a marker for their capability of invasion and metastatic potential.

Antibody Specificity

ANCA-associated vasculitis and lupus-like syndrome caused by methimazole.

A 24-year-old woman with Graves' disease treated with methimazole for 4 years, developed recalcitrant ulcers on the lower legs. Histological studies demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition. Laboratory investigation revealed lupus-like abnormalities (leucocytopenia, positive antinuclear and antidouble strand (ds) DNA antibodies, and positive ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In addition, leucocytopenia and the immunological abnormalities soon faded. Although lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis is a rare complication. To the best of our knowledge, this is the first report describing ANCA-associated vasculitis caused by methimazole.

Adult

Unsei-in inhibits rheological activity of leukocytes: mechanism of action in neutrophil-related skin diseases.

To investigate the efficacy of Unsei-in on skin diseases such as Behçet's disease, palmoplantar pustulosis and psoriasis vulgaris, the rheological activity of leukocytes as manifested by adhesiveness, deformability and aggregability was studied in vitro using a micropore filtration method. Unsei-in inhibited the rheological activity of leukocytes at a statistical significance of p < 0.01 in normal individuals whose leukocytes had been stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). It did not, however, inhibit the activity of cells that had not been stimulated by FMLP. In contrast, in Behçet's disease, Unsei-in inhibited rheological activity of non-stimulated leukocytes (p < 0.01) but did not inhibit the rheological activity of FMLP-stimulated leukocytes. In a study using Ouren-gedoku-to and Shimotsu-to, the main constituents of Unsei-in, the latter inhibited the activity of FMLP-stimulated leukocytes in normal individuals (p < 0.02). These results indicate that Unsei-in has an inhibitory effect on rheologically-activated neutrophils, which are involved in the healing mechanisms of the above skin diseases, and it also has a satisfactory effect in the form of a mixture of Shimotsu-to and Ouren-gedoku-to.

Adult

Proton radiotherapy for malignant melanoma of the skin.

BACKGROUND: Malignant melanoma, a tumor with reduced radiosensitivity, has been suggested to be overcome by a high-dose fractionation radiotherapy. The proton beam presents physical characteristics that enable such high-dose irradiation. OBJECTIVE: Our aim is to answer whether or not the proton beam can provide useful treatment for cutaneous melanoma. METHODS: Five primary melanomas (4 acral lentiginous and 1 superficial spreading type) and 3 metastatic lymph nodes of 3 different patients were irradiated using the proton beam with a total dose of around 100 Gy fractionated into single doses of approximately 10 Gy. RESULTS: All the macular lesions and a tumor lesion of primary melanoma disappeared completely, and other tumor lesions regressed by 80-90%. The 3 metastatic lymph nodes also regressed by 50-90%. No severe radiation-related complication occurred. CONCLUSION: Proton radiotherapy may prove to be a useful therapeutic modality for the management of cutaneous malignant melanoma.

Aged

Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA-salt hypertensive rats.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.

Animals

Subcutaneous pheomycotic cyst of the finger caused by Exophiala jeanselmei: association with a wooden splinter.

A 58-year-old man with mild glucose intolerance noted a subcutaneous cystic nodule on the ventral aspect of his ring finger. He had experienced trauma to the finger while gardening five weeks before the lesion occurred. Exophiala jeanselmei was isolated and identified on culturing of aspirate from the cystic nodule. The nodule was then removed surgically, and a wooden splinter was found close to the subcutaneous fibrous cyst, suggesting that the causal organism had entered the subcutaneous tissue with the wooden splinter.

Cysts