An atypical myelodysplastic syndrome with t(9;12)(q22;p12) and TEL gene rearrangement.
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Biomedical subjects
Publications and source records attributed to Y Kuno.
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A 74-year-old Japanese man developed a reddish, indurated plaque composed of multiple nodules on his right axilla. Histopathologic examination showed a solid tumor that extended from the upper dermis into the subcutis, with both inter- and intracellular lumen formation, cellular arrangement in single files, a fibrotic reaction around the tumor cells, and the presence of mucinous material in the cytoplasm. There was both nuclear and cytoplasmic pleomorphism. Both lysozyme and GCDFP-15 were identified in the tumor cells. Electron microscopic examination showed periluminal condensation of the cytoplasm. Because thorough clinical and laboratory examinations were unremarkable, we regarded this to be a case of primary adenocarcinoma with signet ring cells of the axilla. The neoplasm might have differentiated toward the apocrine sweat glands or the mammary glands. Radiation therapy was effective to some degree. This seems to be the first reported case in which adenocarcinoma with signet ring cells of the skin affected a site other than the eyelids.
We report a 70-year-old woman who developed recurrent multiple ulcers and residual atrophic scars on her legs and feet. The histology showed fibrinoid material in the dermal vessel walls causing partial to complete occlusion of the lumina. Capillary tufting and dilatation were also noted in the dermis. There was no vasculitis or panniculitis. Extravasated red blood cells were seen throughout the dermis; these were engulfed by benign-appearing histiocytes around the dermal-fat junction. As she was generally well and there was no evidence of the presence of cytophagic cells in her extracutaneous organs, she was diagnosed with regional phagocytic histiocytoses supposedly triggered by extravasated red blood cells.
Adenocarcinoma with signet ring cells (ASRC) is a rare skin neoplasm whose histology shows a solid tumor intermingled with signet ring cells in variable numbers. There have been only ten reported cases. All were elderly males affected on the eyelids except for a single case in the axilla. Two new patients with ASRC of the axilla are described. In both of them, immunohistochemical studies revealed neoplastic cells that had differentiated toward apocrine glands. These are the second and third reported cases of ASRC in the axilla, one of them is the first ASRC case in a female. It seemed that the apocrine sweat gland or aberrant breast tissue in the axilla were possible origins of these tumors.
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The spinal action of pro-inflammatory agent, prostaglandin E1 (PGE1) was investigated in rats, using formalin test. Sprague-Dawley rats were implanted with chronic intrathecal catheters. PGE1 0.25 microgram or 2.5 micrograms injected intrathecally. Ten minutes later, 5% formalin 50 microliters was injected to the dorsum of one hindpaw. For the time-response analysis, the total number of flinches were counted and expressed as responses per minute for each rat. For the dose response analysis, the cumulative responses per minute over the first 5 min (phase 1) and the interval 10-60 min (phase 2) following the formalin injection were calculated for each rat. PGE1 2.5 micrograms produced a significant increase of flinching in both phase 1 and phase 2. Dose dependent increase of flinching was seen only in the phase 2. Touch evoked allodynia was observed after the injection of PGE1 2.5 micrograms, which lasted about 50 minutes. The enhanced flinches induced by intrathecal PGE1 were antagonized by the coadministration of MK-801, hemoglobin or methylene blue. Allodynia was antagonized only by coadministration of methylene blue. These results indicate that hyperalgesia induced by spinal PGE1 in both phase 1 and phase 2 of the formalin test involves an increased release of glutamate and the activation of NMDA receptor in the spinal cord. The mechanism of allodynia observed in the rats given high dose of PGE1 differs from that of hyperalgesia.
BACKGROUND: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. OBJECTIVE: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. METHODS: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed-PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. RESULTS: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/beta-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects (P =. 0424, P =.0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells (r = 0.506, P =.0023) and the histamine content (r = 0.480, P =.0040). CONCLUSIONS: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose.
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To search for the signaling events in colorectal carcinoma relevant to its tumorigenesis, we investigated the activity of mitogen-activated protein kinase (MAPK) in human colorectal carcinoma tissues and paired normal tissues. Of 64 cases examined, approximately 75% (48 cases) showed tumor-specific activation of MAPK by in situ kinase renaturation assay, as well as in vitro kinase assay with immunoprecipitated MAPK. In addition, tumor-specific activation of MAPK was associated with the activation of MAPK kinase in the cases we examined. However, no clear correlation of MAPK activation with lymph node involvement, metastatic rate, stage, histological classification, age or sex was observed. These results suggest that the MAPK pathway is involved in colorectal tumor development, but its activation alone is not sufficient for malignant conversion. In contrast to colorectal carcinoma, gastric carcinoma tissues showed a lower rate of MAPK activation, suggesting that the signaling pathway activated in colorectal carcinoma tissues may differ in part from that of gastric carcinoma.
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The enhanced effects due to the combined use of oral administration of S-1 and intraperitoneal administration of Cisplatin (CDDP) were examined with gastric cancer xenografts (NUGC 4). S-1, a new anticancer drug, was daily administered at 10 mg/kg (qld x 5 x 3 weeks). 5-FU level in blood was 1 microgram/ml at two hours after the treatment. Antitumor activity was not found in mice with only the CDDP treatment. But antitumor activity by S-1 and daily low-dose (1 mg/kg) or intermittent treatment (5 mg/kg) of CDDP showed better results than daily S-1 treatment. The daily low-dose CDDP treatment showed similar efficacy to the intermittent administration at the same total dose, but the daily low-dose CDDP treatment was better in the light of toxicities. These results suggest that treatment with S-1 and daily low-dose CDDP was effective for gastric cancer.
We reported a 72-year-old female patient who developed acute leukemia following a long course of polycythemia vera (PV). For 12 years she had been treated with phlebotomy, nimustine, busulfan, hydroxyurea and irradiation on splenomegaly. In November 1995, her peripheral blood smear showed blast of 30%. Bone marrow blasts were microscopically as well as electromicroscopically peroxidase-negative and CD7 and HLA-DR positive. Six months later, the blasts were positive for CD7, CD34 and HLA-DR. On the basis of morphologic, biochemical and immunophenotypic features, the patient was diagnosed acute leukemia, probably arising at a primitive multipotential stem cell level. She failed to respond to the various combination therapy including prednisolone, vincristine, cytarabine, daunorubicin and etoposide. The stem-cell-leukemia transformation in PV occurs rarely and may be refractory to chemotherapy.
Spinal NMDA receptors are involved in hyperalgesia and chronic pain. The activation of spinal NMDA receptor results in the production of nitric oxide in the second order neurons in the spinal cord dorsal horn. We investigated the effects of intrathecally administered nitroglycerin (NTG) which releases nitric oxide in the cell. Formalin test which reflects phasic and tonic nociception was used as a nociceptive measure in rats with chronically implanted intrathecal catheters. Intrathecal injection of NTG resulted in the increase of flinching behavior induced by formalin injection to one paw in phase 1 (phasic) and phase 2 (tonic) responses in a dose-dependent manner. Intrathecally administered NMDA antagonist, MK-801 (MK) dose-dependently inhibited the effect of NTG but the effect was significant only in the phase 2 of the formalin test. MK given after formalin injection had significantly less effect on the phase 2 response. L-NAME (NOS inhibitor), MB (guanylate cyclase inhibitor) and HB (nitric oxide scavenger) significantly antagonized the hyperalgesic effect of NTG in the phase 2 of the formalin test. These results show that nitric oxide plays an important role in producing hyperalgesia in the spinal cord acting postsynaptically as well as pre-synaptically.
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We report herein the case of a 57-year-old man in whom malignant lymphoma originating in the gastric remnant was confirmed 25 years after a subtotal gastrectomy with Billroth II reconstruction had been performed for gastric ptosis. Gastroscopy revealed an ulcerated tumor on the fornix, and histologic examination of the endoscopic biopsy specimens demonstrated malignant lymphoma. Thus, total gastrectomy with splenectomy, pancreatectomy, and resection of the previously anastomosed jejunal stoma were performed. Histologic examination of the stomach remnant confirmed a diagnosis of B-cell lymphoma of the large-cell type. Although we were unable to study the surgical specimen from the initial operation, the possible relationship between pseudolymphoma and malignant lymphoma has been presented in the literature, which is reviewed following this case report.
A review of mainly histopathologic factors associated with the survival of patients with malignant melanoma was carried out in a retrospective study of 124 Japanese patients treated at the National Cancer Center Hospital between July 1962 and December 1992. There were 60 females and 64 males, and the median follow-up period was 52.7 months (range, 1.1 to 235.3 months). The histologic features included tumor thickness, level of invasion, histologic subtype, ulceration, pigmentation, and cell type. Melanomas thicker than 1.5 mm (P<0.01) and with ulceration (P<0.001) had a significantly worse prognosis. With regard to histologic type, ten-year survival was 65.1% for acral lentiginous melanoma, 50.7% for nodular melanoma, and 47.0% for superficial spreading melanoma (SSM), there being no significant differences among them. We suggest that the prognosis was affected not by histologic type but by the large radial or vertical growth component. With regard to clinical features, the clinicopathological stage, patient age, and year when the disease was diagnosed were reflected in the prognosis (P<0.001). Multifactorial analysis showed that the most significant prognostic variables were histopathologic type (SSM or other), stage (I and II or III and IV), and patient age (<70 or > or = 70 yr).