Scrotal angiokeratoma in a young man.
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Adult↗
Biomedical subjects
K Kakudo
Publications and source records attributed to K Kakudo.
Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells.
Cell adhesion receptors (eg, integrins and CD44) play an important role in invasion and metastasis during tumor progression. The increase in integrin alpha 4 beta 1 expression on primary melanomas has been reported to significantly correlate with the development of metastases. alpha 4 beta 1 is a cell surface heterodimer that mediates cell-cell and cell-extracellular matrix interactions through adhesion to vascular cell adhesion molecule (VCAM)-1 and to the IIICS region of fibronectin. To test the effects of alpha 4 beta 1 expression on tumor cell metastasis, Chinese hamster ovary cells were transfected with human alpha 4 cDNA. Whereas alpha 4-negative Chinese hamster ovary cells developed only pulmonary metastasis, alpha 4-positive Chinese hamster ovary cells developed bone and pulmonary metastasis in 3 to 4 weeks when injected intravenously into nude mice. Bone metastasis was inhibited by antibody against alpha 4 or VCAM-1. Expression of alpha 3 beta 1, alpha 6 beta 1, or alpha V beta 1 did not induce bone metastasis. Expression of alpha 4 beta 1 also induced bone metastasis in K562 human erythroleukemia cells injected into SCID mice. These results demonstrate that alpha 4 beta 1 can induce tumor cell trafficking to bone, probably via interaction with VCAM-1 that is constitutively expressed on bone marrow stromal cells.
Animals↗
Expression of the fibroblast growth factor receptor-1 in human normal tissues and tumors determined by a new monoclonal antibody.
OBJECTIVE: To characterize the distribution of the receptor for the fibroblast growth factor in human normal tissues and tumors using a new monoclonal antibody. DESIGN: Monoclonal antibodies for a kinase-insert region of fibroblast growth factor receptor-1 (FGFR-1) were generated. We conducted an immunohistological analysis of FGFR-1 using a highly specific antibody we generated, and we examined the distribution of this receptor in normal human tissues and in tumors. RESULTS: Intense positivity of FGFR-1 was observed in astrocytes in the brain, smooth muscles in the uterus, cardiac myocytes, respiratory epithelium in the lung, tubular epithelium in the kidney, acinar cells in the pancreas, follicular cells in the thyroid, and ductal and lobular epithelium in the breast. We also observed FGFR-1 expression in the fibroblasts and the tissue microvasculature. In addition to some nonepithelial tumors, some epithelial tumors expressed FGFR-1, including pancreatic adenocarcinomas, thyroid papillary carcinomas, invasive ductal carcinomas of the breast, lung adenocarcinomas, renal cell carcinomas, and colonic adenocarcinomas. Although FGFR-1 was expressed in colonic adenocarcinomas, which have invasive potential, tubular adenomas, which are noninvasive, did not express FGFR-1. CONCLUSION: We have been able to define the distribution of FGFR-1 in human normal tissues and tumors. Especially in colonic tumors, FGFR-1 expression may lead adenoma cells to invade and grow in the surrounding tissue.
Amino Acid Sequence↗
Establishment of an in vitro cell derived from human angiosarcoma.
We have succeeded in the establishment of a human endothelial cell line derived from a human angiosarcoma. These cells grew as monolayers with a "cobble stone" morphology. The cells produced endothelin and showed Weibel-Palade bodies in their cytoplasm. These findings show that the cells have specific differenciated functions, and might be useful for both fundamental endothelial cell biology and biological investigation of angiosarcoma.
Aged↗
Late occurrence of K-ras gene mutations in the pathogenesis of squamous cell carcinoma of the lung: analysis in sputum.
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Carcinoma, Squamous Cell↗
A new type of human calcitonin receptor isoform generated by alternative splicing.
There are three isoforms of calcitonin receptors (CTRs). The first type (type 1) has 479 amino acids in rat and 482 amino acids in porcine. The second type (type 2) has a 39 amino acid insertion in the second extracellular domain. The third type (type 3) has a 16 amino acid insertion in the first intracellular domain. The CTR which has been isolated from a human ovarian carcinoma cell line belongs to type 3. Using RT-PCR with primers whose sequences correspond to the human CTR cDNA, we analyzed the expression of the CTR transcripts in seven human tumor cell lines and surgical specimens. The CTR m-RNA were found in all samples. Transcripts which were 48bp shorter than that of the type 3 human CTR were detected, but not transcripts of type 2 and type 3. Since the structure of this CTR is same as that of the type 1 rat and porcine CTRs, we termed it the human type 1 CTR. PCR studies using human genomic DNA as a template revealed that the 48bp sequence constitutes an exon. These results indicate that the type 1 and the type 3 human CTRs are generated by alternative splicing and a majority of human CTR transcripts is type 1.
Alternative Splicing↗
Malignant schwannoma of the liver.
Malignant schwannoma is the most common soft tissue sarcoma in adults, but primary schwannoma of the liver is extremely rare. We report an autopsy case of malignant schwannoma of the liver in a 63-year-old man. The tumor involved almost the entire right lobe of the liver. Microscopically, it was composed of moderately pleomorphic spindle cells with hyperchromatic nuclei with mitotic figures. The spindle cells were stained positively with antibodies to both S-100 protein and vimentin. Necrosis was found in the primary tumor. Only four other cases of malignant schwannoma of the liver were found in a review of the literature. Pertinent features of these tumors are discussed.
Fatal Outcome↗
Quantitative analysis of stromal fat content of human parathyroid glands associated with thyroid diseases using computer image analysis.
The stromal fat content in the parathyroid glands and its significance are still controversial. Several methods have also been introduced to evaluate the content in the literature. In an attempt to better understand the significance of stromal fat content, a computer image analyzing system was applied and 62 glands were investigated using routinely processed tissue. Our study revealed that the average stromal fat content was 34.8 +/- 18.7% which was lower than that of other studies. The stromal fat content was correlated with the age, grade of obesity, area of the gland and serum parathormone level; however, no consistent patterns were obtained with other clinical parameters. These results indicate that the change of stromal fat content may be related to the general condition of the patient similar to the change of fat in other organs. However, the decrease of the content may indicate the early change of parathormone secretory activity even if the serum examination shows no evidence of hyperfunction of the glands.
Adipose Tissue↗
Multiple alternative splice isoforms of parathyroid hormone-related peptide mRNA in human cell lines.
Parathyroid hormone-related peptide (PTHrP) is thought to be responsible for hypercalcemia in some patients with malignant tumors. The PTHrP gene has seven exons, giving rise to three types of PTHrP isoform through alternative splicing. We studied the expression of mRNAs in 14 human cell lines using the reverse transcription-PCR method, to examine tissue-specific expression. All the cell lines expressed at least two types of PTHrP transcript. Most cell lines expressed all four types of PTHrP mRNA isoform. However, a rhabdomyosarcoma cell line, RD, and a bladder carcinoma cell line, T24, expressed only two types. These results may suggest that PTHrP mRNA is expressed in the majority of tumor and normal tissues and that it shows less tissue- or tumor-specificity.
Base Sequence↗
Different migration patterns of antigen-presenting cells correlate with Th1/Th2-type responses in mice.
Antibodies are produced when antigen-presenting cells (APC) pulsed with an antigen are injected intravenously (i.v.) into BALB/c mice, but subcutaneous (s.c.) injection of such APC causes delayed-type hypersensitivity (DTH). To identify the anatomic sites where T and B cells are activated, we labelled splenic dendritic cells (DC) with a fluorochrome, PKH 26, injected them i.v. or s.c., and used the label to locate them. When the DC were injected i.v., germinal centres in the spleen were hyperplastic on day 1. Most DC moved to T-dependent areas of the white and red pulp on day 1 and remained there at least until day 5, but no DC migrated into the lymph nodes. When the DC were injected s.c., they were in the sinus on day 1 and had entered T-dependent area of draining lymph nodes only by day 3; hyperplasia of germinal centres in the spleen and migration of DC into the spleen were not found. We used the polymerase chain reaction (PCR) to study which mice had spleen cells and lymph node cells that produced the cytokines interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma). In the sensitization phase, day 1 after DC injection i.v., almost all IL-10 transcript was found in spleen cells, but after DC injection s.c., IL-2 message was most abundant in lymph node cells. The expression of mRNA for IL-4 and IFN-gamma in mice that received DC i.v. was not different from that in mice that received DC s.c. in this phase. Immunohistochemical staining showed that cells stained for IL-10 were in the T-dependent area of the spleen from mice that received DC i.v. 1 day after the injection. Three days after the injection of DC i.v., cells stained for IL-10 were in the germinal centres as well. The number of such cells in the spleen of mice that received DC i.v. was significantly more than that in mice that received DC s.c. IL-10 may be important in development of TH2 response.
Animals↗
The role of antigen-presenting cells in the regulation of delayed-type hypersensitivity. II. Epidermal Langerhans' cells and peritoneal exudate macrophages.
A new mechanism for regulation of delayed-type hypersensitivity (DTH) was investigated. The subcutaneous injection without adjuvant of syngeneic epidermal Langerhans' cells (LC) pulsed with keyhole limpet hemocyanin (KLH) into BALB/c mice gave rise to DTH upon challenge of the ear with the same antigen. When such cells were transferred intravenously, DTH did not occur, although the titer of anti-KLH antibodies was high. Peritoneal exudate macrophages (M phi) pulsed with KLH gave rise to neither DTH nor antibody production. The intravenous transfer of KLH-pulsed LC into mice immunized subcutaneously with KLH in complete Freund's adjuvant at the same time (in the sensitization phase) had a suppressive effect on DTH in an H-2-restricted way. M phi did not have immunoregulatory effects. When radiolabeled LC and M phi were transferred intravenously, they migrated into the spleen, but when they were transferred subcutaneously, they stayed in the skin or migrated into the lymph nodes. In splenectomized mice immunized with KLH, the intravenous transfer of LC pulsed with KLH neither caused the production of anti-KLH antibodies nor suppressed DTH. When Ia was expressed on the surface of M phi, the cells could present antigens, as LC could. These findings suggest that the anatomic sites at which an antigen is presented (i.e., spleen or draining lymph nodes) rather than the kind of cell that first presents an antigen to the immune system is important in deciding whether the immune response that takes place is DTH or antibody production.
Animals↗
Pearson's marrow/pancreas syndrome: a histological and genetic study.
A patient with features of Pearson's syndrome who presented with transfusion-dependent severe macrocytic anaemia, neutropenia, thrombocytopenia, and insulin-dependent diabetes mellitus in the neonatal period is described. His bone marrow was characterized by marked vacuolization of myeloid precursors and ringed sideroblasts. Autopsy examination revealed fibrosis and steatosis of the liver, reduction in the size and number of the islets, fibrosis and acinar atrophy of the pancreas, vacuolation of renal tubules, glomerulosclerosis, and "ragged red" fibres of skeletal muscles. Analysis of mitochondrial DNA (mtDNA) from the autopsied liver and skeletal muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 7374 bp. The deleted region was bridged by a single nucleotide, C, in normal mtDNA.
Anemia, Sideroblastic↗
Changes in synovial fluid N-acetyl-beta-glucosaminidase activity in the human temporomandibular joint with dysfunction.
beta-Glycosidases (N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase) were assayed in temporomandibular joint (TMJ) synovial fluid obtained from 23 patients with closed lock TMJ internal derangement (ID), four with closed-lock TMJ osteoarthritis (OA), and 13 with normal controls (N). Synovial fluid was collected from the upper joint space after injecting 1.5 ml of 1% lidocaine three times. The specific activity of N-acetyl-beta-glucosaminidase increased significantly both with ID (p < 0.01) and with OA (p < 0.001), along with increases in the activity of N-acetyl-beta-galactosaminidase (p < 0.05 with ID and p < 0.01 with OA) and in beta-glucuronidase (p < 0.05 both with ID and OA). The N-acetyl-beta-glucosaminidase activity with OA was also significantly higher (p < 0.001) than with ID. These findings suggest that N-acetyl-beta-glucosaminidase activity in the TMJ synovial fluid reflects the degree of TMJ dysfunction.
Acetylglucosaminidase↗
Effects of ipriflavone on calcitonin synthesis in C cells of the rat thyroid.
Ipriflavone is known to stimulate calcitonin (CT) secretion from the thyroid glands of female animals, but the exact mechanism of this action remains unknown. In the present study, an increase of CT production in thyroid C cells of female rats, but not of male rats, was proven immunohistochemically. Furthermore, the parallel increase of CT mRNA in those thyroid glands was confirmed by Northern blot analysis. These results proved that ipriflavone stimulates not only CT secretion but also CT synthesis in thyroid C cells and that the changes were gender dependent (greater in females). In order to investigate the effect of estrogen on the ipriflavone-induced increase of CT in female rat thyroid gland, CT and CT mRNA in the thyroid glands of untreated, ovariectomized, and estrone-treated (postovariectomy) rats were examined by both immunohistochemistry and Northern blot technique. Serum levels of CT and calcium were also examined. Against expectation, estrone failed to produce any significant effect on the ability of ipriflavone to induce CT synthesis and secretion.
Animals↗
Small cell carcinoma of the stomach: an immunohistochemical and electron microscopic study.
A 4 x 6 cm ulcerative mass in the antrum was found to consist of papillary adenocarcinoma in the surrounding wall and the small round cell neoplasm at its base. Immunohistochemical staining revealed that elements of the papillary adenocarcinoma were positive for carcinoembryonic antigen, epithelial membrane antigen, keratin, endocrine granule constituent, and CA19-9, while components of the small cell carcinoma were weakly positive only for neuron-specific enolase. In one portion of the small cell carcinoma, particularly large cells with pleomorphic nuclei which were intensely positive for desmin were detected. Electron microscopic examination revealed dense-cored granules and intercellular junctions in the small neoplastic cells and bundles of intermediate filaments in the desmin-positive large cells. These findings suggest that ultrastructural examination is vital in diagnosis of small cell carcinoma and they reveal the capability of this carcinoma toward multidirectional differentiation.
Adenocarcinoma, Papillary↗
The role of antigen-presenting cells in the regulation of delayed-type hypersensitivity. I. Spleen dendritic cells.
A previously unreported mechanism for the induction of delayed-type hypersensitivity (DTH) was studied in detail. The subcutaneous injection (without adjuvant) of spleen dendritic cells (DC) pulsed with keyhole limpet haemocyanin (KLH) into syngeneic BALB/c mice caused DTH when the ear was later injected with the same antigen. When KLH-pulsed DC were transferred intravenously, DTH was not induced, although the titre of anti-KLH antibodies rose after such transfer. The intravenous transfer of KLH-pulsed DC into mice immunized subcutaneously with KLH in complete Freund's adjuvant (CFA) at the same time (in the sensitization phase), but not when the ear was challenged with KLH (in the effector phase), had a suppressive effect on DTH, in an H-2-restricted way. When radiolabelled DC were transferred intravenously, they migrated into the spleen, but when transferred by subcutaneous injection, they stayed in the skin or migrated into the lymph nodes. In splenectomized mice immunized with KLH, the intravenous transfer of KLH-pulsed DC did not cause production of anti-KLH antibodies and did not suppress DTH. These findings suggest that the anatomical sites in which antigens are presented (i.e. the spleen or lymph nodes) rather than the type of cell that first presents antigens to the immune system governs whether DTH or antibody production is induced. Antibody production was induced when antigens were presented in the spleen.
Animals↗
Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas.
A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma.
ABO Blood-Group System↗
The role of antibodies in the regulation of delayed-type hypersensitivity.
The contribution of B cells and antibodies to the regulation of delayed-type hypersensitivity (DTH) was investigated in mice rendered B-cell-deficient by treatment with anti-mu antibodies. In normal rabbit immunoglobulin (Ig)-treated mice as well as normal mice, the intravenous injection of a large amount of keyhole limpet haemocyanin (KLH) suppressed DTH, and serum titres of the anti-KLH antibody were significantly elevated. However, in anti-mu-treated mice, the intravenous injection of a large amount of KLH could not induce either suppression of DTH or the elevation of anti-KLH antibody titres. The transfer of anti-KLH antibodies suppressed DTH in a H-2 non-restricted, probably Igh-restricted, way in anti-mu-treated mice. In addition, the transfer of anti-KLH antibodies induced effector-phase suppressor T cells whose phenotype was L3T4-, Lyt-2+. We concluded that antibodies play a significant role in the regulation of DTH.
Animals↗