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Biomedical subjects

F Otsuka

Publications and source records attributed to F Otsuka.

At least 109 records · Page 6Linked to original sources

Papillary eccrine adenoma: immunohistochemical studies of keratin expression.

Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. In the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochemical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intraluminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands.

Adenoma, Sweat Gland↗

Isolation of a cDNA encoding a tyrosine kinase expressed in murine skin.

Tyrosine phosphorylation is widely recognized as playing an important role in cell differentiation, proliferation and carcinogenesis. We used the polymerase chain reaction (PCR) method to identify protein tyrosine kinases that were expressed in the skin. Mixed oligonucleotide probes were used to amplify and screen neonatal murine skin mRNA for clones encoding amino acid contiguities, the conservation of which is characteristic of the protein tyrosine kinase family. When the PCR products were sequenced, a novel clone encoding protein tyrosine kinase, PTK70, was identified. A full-length cDNA was isolated from a mouse thymus cDNA library. The nucleotide and deduced amino acid sequence showed that it featured src-homology (SH) 2 domain, SH3 domain and kinase domain like other src family protein tyrosine kinases, but lacked the N-terminal myristylation site and C-terminal tyrosine residue. Although the mRNA of PTK70 was detected in various tissues ubiquitously, the degree of its expression differed among tissues. Murine skin is one in which PTK70 was expressed strongly, with its expression being much stronger in the epidermis and in the cell line derived from murine keratinocytes than in those from melanoma or fibroblast cell lines. These evidences suggest that PTK70 may be involved in proliferation or differentiation of keratinocytes in the skin.

Amino Acid Sequence↗

In vitro macro- and microautoradiographic localization of V1 and V2 receptors in the rat kidney using OPC-21268 and OPC-31260.

To elucidate the precise localization of vasopressin (VP) V1 and V2 receptors in the kidney, we utilized in vitro macroautoradiography (macro-ARG) and microautoradiography (micro-ARG) of these receptors in Wistar rat kidneys. This was done by using OPC-21268 and OPC-31260, two newly developed selective V1 (OPC-21268) and V2 (OPC-31260) receptor antagonists. For macro-ARG, 10-microm kidney sections were incubated with Tris-HCl buffer containing [3H]-VP with or without unlabeled ligand (VP, OPC-21268, or OPC-31260) at 20 degrees C for 40 min. These sections were then loaded into X-ray cassettes with Hyperfilm-[3H] and exposed in the dark for 2 months. The autoradiograms were quantitatively analyzed by using the research analysis system RAS 1,000; the V1 and V2 receptors were quantitated by subtracting the nonspecific binding (incubated with OPC-21268 and OPC-31260, respectively) from the total binding. To assess a more precise localization of the V1 and V2 receptors, we also investigated the micro-ARG of the renal V1 and V2 receptors by dipping the kidney section slides used for macro-ARG into a photographic emulsion and observing the receptors under light microscopy. [3H]-VP binding to the rat kidney was completely displaced by unlabeled excess VP, but not by unlabeled angiotensin II, indicating that [3H]-VP binding was specific for VP receptors. Computerized quantification showed that V2 receptors, visualized by OPC-31260, were the predominant type of VP receptor in the kidney. Conversely, V1 receptors, visualized by OPC-21268, were fewer in number. V1 receptors were partly localized to the glomerulus, cortical vessels, interstitial cells, and the medullary vessels. The V2 receptors localized to the collecting ducts and medullary tubules. Our findings indicated that renal V1 and V2 receptors can be detected by in vitro macro- and micro-ARG by using OPC-21268 and OPC-31260.

Animals↗

A case of primary hyperparathyroidism accompanying multiple myeloma.

We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I degree HPT) remains unknown. Although the co-existence of MM and I degree HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.

Aged↗

Gestational thyrotoxicosis manifesting as wernicke encephalopathy: a case report.

The thyroid gland is physiologically stimulated in normal early pregnancy. This stimulated thyroid function is occasionally termed "gestational transient thyrotoxicosis". The cause of this thyrotoxicosis has been clarified to closely it associate with human chorionic gonadotropin (hCG). We encountered a pregnant patient with hyperemesis and thyrotoxicosis, who manifested symptoms of Wernicke encephalopathy. Although her serum hCG concentration transiently increased in accordance with the thyrotoxicosis, it was within normal limits for the gestational week. Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy. This case suggests that pregnant patients with hyperemesis should undergo careful endocrinological and neurological evaluations.

Adult↗

Manifestation of primary hyperthyroidism after pituitary adenomectomy: a case report.

We report a 47-year-old Japanese man who presented with visual disturbance due to a pituitary tumor with suprasellar extension. The patient had mild secondary hypothyroidism preoperatively, and was started on administration of levothyroxine sodium immediately before transsphenoidal surgery. After the operation, levothyroxine sodium was continued for several months. Pathological examination of the surgical specimen, together with endocrinological investigation revealed that the suprasellar tumor was a FSH-producing pituitary adenoma. Since 3 months after the operation, he has developed muscle weakness and finger tremor. He was found to be thyrotoxicosis, and levothyroxine sodium was discontinued. Seven weeks after levothyroxine sodium was discontinued, thyrotoxicosis continued, with a positive thyrotropin binding inhibitory immunoglobulin (TBII) and a high diffuse 123I-uptake by the thyroid. He was started on thiamazole 30 mg/day. Although his thyroid dysfunction improved within 2 months, hyperthyroidism worsened repeatedly on attempts to discontinue thiamazole, and he required continuous treatment at 2.5 mg/day. Patients with occult autoimmune thyroiditis rarely progress to thyrotoxicosis after operations on other endocrine organs such as the adrenal or parathyroid gland. In patients with pituitary adenoma, thyroid function and thyroid-associated autoantibodies should be investigated pre- and post-operatively.

Adenoma↗

IDDM accompanied by a growth hormone-producing pituitary adenoma. A case report.

CASE HISTORY: A 30-year-old Japanese man who presented with recurrent ketoacidosis caused by IDDM was found to have increased secretion of growth hormone (GH). On initial cranial magnetic resonance imaging (MRI), no pituitary lesion was detected; however, a pituitary microadenoma was found 2 years later during a repeat MRI. In spite of the hypersecretion of GH, serum IGF-I was dramatically suppressed. Transsphenoidal surgery was performed to resect the pituitary tumor that was histologically an acidophilic pituitary adenoma. Although the GH excess rapidly improved postoperatively, the IGF-I level remained low. Subsequent insulin therapy initiated 1 year after the operation elevated the serum IGF-I level to within the normal range. DISCUSSION: The first case of coexistent IDDM and a GH-producing pituitary adenoma suggests that patients with uncontrolled IDDM may develop GH hypersecretion. Furthermore, the low IGF-I levels may be closely associated with the GH excess and with the development or progression of GH-secreting pituitary adenomas.

Adenoma↗

DNA-ploidy abnormalities are a reflection of the metastatic potential of malignant melanoma. Microfluorometric DNA analysis.

Using DAPI (4',6-diamidino-2-phenylindole)-DNA microfluorometry, we examined the nuclear DNA-ploidy abnormalities of 15 primary malignant melanomas and their 20 corresponding metastases. They all presented the aneuploid DNA histographic pattern. When the DNA index value was calculated as the reflection of DNA-ploidy abnormalities, it was found to be significantly higher in the metastases (2.07 +/- 0.50) than in the primary tumors (1.76 +/- 0.50) (p < 0.01). Sixteen (80%) of the metastatic tumors had a higher DNA index value than their primary tumors, whereas the remaining four (20%) had a lower value. The difference in the DNA index values between the primary and metastatic tumors did not correlate to any other conventional prognostic variables (e.g. histologic type, level, and thickness). When we added 15 non-metastatic melanomas to the above 15 primary melanomas and evaluated the predictors for metastasis using multivariate stepwise logistic regression analysis, the DNA index value of the primary melanomas was found to be the most reliable risk factor. These results suggest that primary melanoma cell populations, having high DNA index values, are usually responsible for subsequent metastasis, and that hence, DNA-ploidy abnormalities of primary melanomas are likely to provide useful information for patient potential with regard to metastasis.

Adult↗

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↗

Alteration of human melanoma gangliosides by IFN-gamma, IL-2, and IL-4.

In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-gamma increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.

Gangliosides↗

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↗

Leukopenia and rheological anomalies in leukocytes during hemodialysis in patients with chronic renal failure.

In order to clarify the relation between leukopenia during hemodialysis and leukocyte adhesiveness, the number of circulating leukocytes, their filterability through 5 micron diameter pores, and the concentration of neutrophil elastase in plasma were measured in peripheral blood collected at the beginning of hemodialysis (dialyzer, cuprophane membrane), 15 min into dialysis, and end of dialysis (duration of dialysis, 180 min) in 15 patients with chronic renal failure. Leukopenia was most marked at 15 min in all patients. In accordance with the change in number of circulating leukocytes, the filtration time of the leukocytes, as determined by a modification of the Nuclepore filtration method (filtered blood volume 0.5 ml, leukocyte count 2,500 microliters, suction pressure 10 cm H2O temperature 37 degrees C) was significantly longer at 15 min versus the beginning and end of the dialysis (p < 0.005 and p < 0.025, respectively). Addition of the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP; 20 nM), to the suspensions immediately increased the leukocyte filtration time. Such FMLP-induced increases were significantly greater at 15 min versus the beginning of dialysis (p < 0.05). This heightened sensitivity of cells to FMLP appeared to persist until the end of dialysis (p < 0.05 versus the beginning). Plasma levels of neutrophil elastase were highest at the end of dialysis versus those at the beginning and after 15 min (both p < 0.005). Results suggest that the changes in filterability of leukocytes may be related to decreases in their number in the circulation. Neutrophil elastase appeared to accumulate in plasma so that its maximal value at the end of dialysis would reflect the preceding changes in leukocyte rheology.

Adult↗

Psoriatic arthritis and hypopyon-iridocyclitis. Possible mechanism of the association of psoriasis and anterior uveitis.

BACKGROUND: We present a 32-year-old Japanese man with psoriatic arthritis who developed recurrent episodes of hypopyon-iridocyclitis associated with exacerbations of the arthropathy. OBJECTIVE: To evaluate the mechanism of the association between psoriasis and uveitis, we analyzed the rheological characteristics of the patient's peripheral blood neutrophils during attacks and during remissions. METHODS: The rheological activity of neutrophils was determined by the micropore filtration method. It was expressed as micropore filtration time when a neutrophil-erythrocyte suspension passes through a micropore filter (pore size 5 microns). RESULTS: The micropore filtration time in this patient was longer than that of healthy control subjects (p < 0.01) and of psoriatic patients without uveitis (p < 0.05); it was also longer during the appearance of the eye disorder with the exacerbation of psoriatic arthritis than during remissions. CONCLUSIONS: Activated neutrophils in the peripheral blood of our patient were probably responsible for the attacks of hypopyon-iridocyclitis as well as the exacerbation of psoriatic skin lesions and/or arthritis.

Adult↗

A case of Schmidt syndrome accompanied by a pituitary adenoma.

Schmidt syndrome consists of adrenal insufficiency and Hashimoto's thyroiditis, which are probably caused by an autoimmune process. We encountered a patient who manifested severe generalized fatigue due to Schmidt syndrome recurrently. The endocrinological examination tests on the patient showed that the increase in thyroid stimulating hormone (TSH) and ACTH concentrations were not remarkable, despite hypo-function of the peripheral glands. Subsequent cranial magnetic resonance imaging (MRI) exhibited the existence of a pituitary tumor. The pathological findings on the resected tumor and endocrinological stimulation tests proved that the tumor was a FSH-producing adenoma. Although involvement of the pituitary region in Schmidt syndrome on rare occasions presents as hypophysitis, no pituitary adenoma has previously been reported in association with this syndrome. We present a patient with Schmidt syndrome and an accompanying FSH-producing pituitary adenoma. The coexistence of these disorders suggests that the functioning pituitary tumor might be considered as a pituitary lesion in Schmidt syndrome.

Adenoma↗

Manifestation of subclinical diabetes insipidus due to pituitary tumor during pregnancy.

We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

Adenoma↗