Search PubMed⌕ Search

Biomedical subjects

K Horikawa

Publications and source records attributed to K Horikawa.

At least 91 records · Page 5Linked to original sources

Ganglioside, adhesion molecule, and HLA antigen expression in basal cell carcinoma lesions.

The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by immunoperoxidase staining of 27 surgically removed BCC lesions with antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC cells, which was corroborated by thin layer chromatography immunostaining with MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion molecules tested vitronectin receptor and CDw44 were found in up to 70% of the lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC cells in five and three lesions removed 24 and 48 h, respectively, following the intralesional injection of gamma-interferon. The latter enhanced HLA Class I antigen expression and induced ICAM-1 expression by the surrounding keratinocytes; furthermore gamma-interferon induced HLA Class II antigen expression by a small percentage of BCC cells in three lesions. These results suggest that malignant transformation of keratinocytes is associated with a selective loss of susceptibility to induction by cytokines of ICAM-1 expression. Besides confirming the low HLA Class I and Class II antigen expression by BCC cells, the present investigation has shown a differential expression of distinct monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has shown that HLA Class II antigens can be induced on BCC cells by cytokines.

Aged↗

Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.

The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1- and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP), 1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]-pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76 times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than 1,6-DNBP. It is suggested that the mutagenic activation differs with the position of NO2 substitution in the chemical structure. A nitro derivative with NO2 substitution at the 3 position of the aromatic ring of BP was more mutagenic than that with the substitution at the 1 or 6 position. The reducibility of DNBPs was then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein, when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was readily reduced by a microsome enzyme to form an amino derivative. The result suggests that these compounds have a structure-activity relationship between mutagenicity and NO2 substitution of BP.

Animals↗

A pitfall in determining the globulin/albumin ratio in amaranth grains.

In amaranth grains (Amaranthus hypochondriacus L. and Amaranthus cruentus L.), there were two albumin (Alb) fractions, Alb-1 and Alb-2; Alb-1 was extracted with water or 0.5 M NaCl, and Alb-2 was extracted with water after extracting Alb-1 and globulin. The amount of Alb-2 comprised about 30% of the total albumin and globulin content. Little or no measurable protein corresponding to the amaranth Alb-2 was extracted from seeds of buckwheat (Fagopyrum esculentum Moench), quinoa (Chenopodium quinoa L.), or barley (Hordeum vulgare L. cv Sekitorisai-1). That the globulin/albumin ratio (G/A) in amaranth grains has been conflicting among investigators probably accounts for the consideration of Alb-2 during extraction. We here report the revised G/A ratio of 0.3-0.4.

Albumins↗

Increased plasma decay-accelerating factor levels in paroxysmal nocturnal hemoglobinuria.

Decay-accelerating factor (DAF) is a complement regulatory membrane protein that is often absent from the cell surface of blood cells in paroxysmal nocturnal hemoglobinuria (PNH). DAF has also recently been found in the body fluids of healthy individuals. However, its precise structure and biological significance are not yet clear. To clarify the clinical and pathological implications of free DAF, we measured plasma DAF levels in PNH patients, using a newly developed quantitative enzyme-linked immunosorbent assay (ELISA), with a measurable range between 0.2-12 ng, for soluble DAF. ELISA assays revealed significantly increased plasma DAF levels in PNH patients (258 +/- 150 ng/ml, mean +/- S.D., n = 9) as compared with healthy controls (80 +/- 41 ng/ml, n = 17) (p less than 0.01). Taken together with the finding that DAF is synthesized in and released extracellularly from affected PNH cells, plasma DAF levels would be useful for clinical diagnosis and for the quantitative evaluation of the clonal expansion of affected cells in PNH.

Adult↗

[A case of phlebothrombosis of lower extremity and pulmonary embolism due to progesterone].

A case with lower extremity phlebothrombosis and pulmonary embolism caused by progesterone is reported in this paper. The patient is a 64-year-old woman who had been operated on for right breast cancer 22 years before. It was noticed that there was a relapsing cancer on her right shoulder 6 months before this episode. After effective treatment of 5-FU, she had received 1,200mg of Medroxyprogesterone acetate and 30mg of Tamoxifen daily for 4 months. With the complaint of dyspnea and left leg swelling 4 months after above treatment, she was admitted in our hospital. Laboratory data and angiograms showed venous thrombosis in her left leg and pulmonary embolism. Relapsing cancer had already disappeared by the time she was admitted. After discontinuance of these medicines, her condition had improved. Considering these observations, the patient's phlebothrombosis and embolism seem to have been caused by Medroxyprogesterone acetate.

Breast Neoplasms↗

Altered expression of protein kinase C in adult T-cell leukemia cells.

Protein kinase C (PKC) has been shown to be involved in the mitogenic response and in oncogenic cell transformation in many experimental models. We analyzed the expression of PKC in both highly purified leukemic T cells freshly isolated from adult T-cell leukemia (ATL) patients and control T lymphocytes obtained from healthy volunteers. PKC activity was decreased in the ATL cells as compared with the control T cells. Cytosolic PKC activity in the ATL cells was remarkably decreased, whereas particulate membrane PKC activity was similar to the control level. The percentage of PKC activity in the particulate fraction was 34% in the ATL cells and 19% in the control cells. Regarding the altered subcellular localization of PKC activity, phorbol ester-induced translocation of cytosolic PKC was inhibited in some ATL cases. Similarly to the decrease in PKC activity, there was a decrease in the expression of the major PKC isozymes II(beta) and III(alpha) in ATL cells. These results suggest impaired regulation of PKC expression in ATL as well as in many experimental cancers.

Adult↗

Common phenotypic expression of gangliosides GM3 and GD3 in normal human tissues and neoplastic skin lesions.

The expression of gangliosides in non-malignant tissues (epidermis and pigmented nevus) and neoplastic lesions (melanoma, squamous cell carcinoma [SCC] and basal cell carcinoma [BCS]) of the human skin was analyzed immunohistochemically and biochemically to characterize the features associated with malignancy. Immunohistochemical staining with an anti-II3NeuAc-LacCer (GM3) monoclonal antibody (M2590 mAb) and an anti-II3(NeuAc)2-LacCer (GD3) mAb (R24) showed the expression of the gangliosides GM3 and GD3 to vary among the different tissues. M2590 clearly stained epidermal keratinocytes and the tumor cells of BCC and SCC, and strongly stained melanocytes and melanoma cells. In contrast, R24 did not stain epidermal keratinocytes and only faintly stained SCC cells, while it clearly stained BCC cells, and intensely stained melanocytes and melanoma cells. GM3 showed a similar level of staining among the tissue specimens, while the level of GD3 staining was quite variable among the tumor specimens. Biochemical analysis by thin-layer chromatography (TLC) with resorcinol staining and TLC immunostaining with either M2590 or R24 showed both GM3 and GD3 to be commonly expressed by both the normal and malignant skin tissues, including SCC. There was no close correlation between the intensity of immunohistochemical staining and the biochemically detected amounts of these gangliosides. This may have been partly due to the so-called cryptic expression of cell membrane gangliosides. Our results thus suggest that analysis of the tumor-associated expression of gangliosides requires several methods, since the sensitivity of the methods used may have a considerable effect on the diagnostic value of gangliosides as skin cancer markers.

Biomarkers, Tumor↗

Hemolysis of human erythrocytes is a new bioactivity of gangliosides.

Using sheep erythrocytes and liposomes, an inhibitory effect of gangliosides has been shown on the activation of the alternative pathway of complement. However, in studies using human erythrocytes, we found that gangliosides had hemolytic activity that was possibly mediated through activation of the alternative pathway. Pretreatment of human erythrocytes obtained from healthy volunteers or paroxysmal nocturnal hemoglobinuria (PNH) patients with a ganglioside mixture purified from human erythrocytes enhanced their susceptibility to homologous human complement, and resulted in dose-dependent hemolysis. The enhancement was more marked in PNH erythrocytes than control cells. Protease treatment of the ganglioside mixture did not change its hemolytic activity, but sialidase treatment abolished the activity. Among the major erythrocyte gangliosides, II3NeuAc-LacCer (GM3) was the most potent hemolytic agent. Gangliosides purified from bovine brain were also active, while neither nonsialylated glycosphingolipids, the ceramide moiety, or sialic acid alone were active. Sialic acid residues in the ganglioside molecules were essential to this activity, but the amount of the residue or the source of the gangliosides seemed not to be important. Several treatments inhibiting the alternative but not classical complement pathway markedly reduced the ganglioside hemolytic activity. This novel bioactivity of gangliosides was thus suggested to be mediated partly by activation of the alternative pathway.

Chromatography, Thin Layer↗

Concanavalin A-stimulated expression of gangliosides with GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta structure in murine thymocytes.

We analysed the glycolipids of mouse thymocytes before and after Concanavalin A (Con A) or recombinant interleukin-2 (rIL-2) stimulation by TLC-immunostaining with carbohydrate-specific antiglycolipid antibodies. The thymocytes were cultured in serum-free medium in the presence of 500 ng ml-1 Con A, 10 U ml-1 rIL-2 or Con A plus rIL-2 for 6, 12, 24, 48, and 72 h, and were found to start proliferating 24 h after cultivation in the presence of Con A or Con A plus rIL-2, the maximum levels being reached at 72 h and 48 h, respectively, in a thymidine uptake experiment. The concentrations of II3Neu-Gg4Cer, Gg4Cer and IV3GalNAc alpha-Gb4Cer after 48 h Con A stimulation were found to be at almost the original levels. Conversely, II3Neu-Gg3Cer, which was not detected in the thymocytes at the start, began to appear after 48 h stimulation with Con A and Con A plus rIL-2, and IV3Neu-Gg5Cer in the cells 48 h after stimulation with Con A and Con A plus rIL-2 has increased to 41 and 44 times higher than in the original cells, respectively, as judged on TLC-immunostaining with monoclonal antibody YHD-06, which detects the GalNAc beta 1-4(NeuAc or NeuGc alpha 2-3)Gal beta-structure. These results indicate that the increased synthesis of both gangliosides, in other words, the activation of N-acetylgalactosaminyltransferase, is associated with the mitogen-induced proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Detection of 3,6-dinitrobenzo[a]pyrene in airborne particulates.

3,6-Dinitrobenzo[a]pyrene, a new mutagen, was detected in airborne particulates collected in Santiago (Chile). The quantity of the compound in the airborne particulates was very small, accounting for 0.01 micrograms/g of total particulates (0.002 ng/m3 of air) at the lowest concentration. It was found that 3,6-dinitrobenzo[a]pyrene is readily decomposed by UV irradiation at 312 nm. The decomposed product was identified as 3-nitrobenzo[a]pyrene-6-quinone by means of mass spectrometry and proton nuclear magnetic resonance analysis. The mutagenicity of 3,6-dinitrobenzo[a]pyrene was 137,000 revertants/nmole for Salmonella typhimurium strain TA98, less than that for strain TA98/1,8-DNP6, an acetyltransferase-deficient mutant, and more than that for strain YG1024, an acetyltransferase-rich mutant.

Air Pollutants↗

Pulmonary carcinogenicity of 3,9- and 3,7-dinitrofluoranthene, 3-nitrofluoranthene and benzo[a]pyrene in F344 rats.

3,9- and 3,7-Dinitrofluoranthene (3,9- and 3,7-DNF), 3-nitrofluoranthene (3-NF) and benzo[a]pyrene (B[a]P) were tested for pulmonary carcinogenicity by intrapulmonary implantation of the compounds into rat lung. These chemicals were given in various doses as suspensions in beeswax-trycaprylin and the animals were observed for 100 weeks. The control group received no drugs. The incidences of lung tumors were 19/21 (90.5%), 7/10 (70%) and 1/10 (10%) in rats treated with 200, 100 and 50 micrograms of 3,9-DNF, 4/9 (44.4%), 3/10 (30%) and 0/10 (0%) in rats treated with 200, 100 and 50 micrograms of B[a]P, 12/22 (54.5%) in rats treated with 200 micrograms of 3,7-DNF and 1/20 (5%) in rats treated with 1000 micrograms of 3-NF respectively. No lung tumors were found in control rats. The incidence of lung tumors induced by 3,9-DNF was twice as high as that induced by B[a]P, when the equivalent dose levels of the two compounds were compared. Histologically, most of the tumors induced by 3,9- and 3,7-DNF and B[a]P were squamous cell carcinomas.

Animals↗

[A case of complete absence of the left pericardium coexisting with straight back syndrome].

A case of complete absence of the left pericardium coexisting with straight back syndrome in a 30-year-old female is presented. She had been asymptomatic, but was referred to our hospital because of an abnormal finding on a chest X-ray obtained during a routine physical examination. The posteroanterior view of the chest X-ray showed displacement of the right and left cardiac border to the left and bulging of the left cardiac border. The lateral view showed loss of normal thoracic curvature and also demonstrated the straight back syndrome. Echocardiography showed paradoxical movement of the ventricle septum, hyperkinetic movement of the free wall of the left ventricle and enlargement of the right ventricle. Computed tomography and magnetic resonance imaging with an artificial pneumomediastinum clearly showed rotation of the heart into the left hemithorax, prominence of the pulmonary trunk and pneumopericardium. Hence the diagnosis of the complete absence of the left pericardium coexisting with straight back syndrome was made. Congenital defect or absence of the pericardium are rarely reported. Only about 120 cases have been described in Japan. Only a few cases have been diagnosed antemortem. Most of them were found by chance during operations or on installation of an artificial pneumothorax. We suggest that an artificial pneumomediastinum as well as a pneumothorax is useful for the diagnosis of the absence of the pericardium. This is the first reported case of a complete absence of the left pericardium coexisting with straight back syndrome.

Adult↗

[Serum deoxythymidine kinase activity in adult T-cell leukemia].

Serum deoxythymidine kinase activities (s-TK) of the patients with adult T-cell leukemia (ATL), carriers and healthy persons were measured, using a recently developed TK assay with 125I-iodo-deoxyuridine as a substrate. The mean s-TK values were 3.3 +/- 2.7 U/l (n = 21) in normal subjects (HTLV-1(-)), 4.7 +/- 5.0 U/l (n = 35) in carriers, 9.8 U/l (n = 3) in smoldering ATL and 26.7 U/l (n = 6) in chronic ATL. In the patients with acute ATL, the mean s-TK values before and after chemotherapy were 80.9 U/l (n = 2) and 11.6 U/l (n = 4), respectively. In the follow-up studies of the patients with acute ATL, the changes of s-TK levels revealed earlier than those of serum LDH levels. It is suggested that s-TK activity is more useful than LDH as a parameter of monitoring treatment in ATL.

Biomarkers, Tumor↗

Altered expression of gangliosides in erythrocytes of paroxysmal nocturnal hemoglobinuria.

In paroxysmal nocturnal hemoglobinuria (PNH), impaired glycosyl-phosphatidylinositol (PI)-anchoring of membrane proteins such as decay-accelerating factor has been known to lead to increased susceptibility to complement. Moreover, abnormal expression of non-PI-anchoring glycoproteins such as C3b/C4b receptor (CR1) or glycophorin-alpha also has been shown in PNH. Therefore, we biochemically analyzed glycosphingolipids (GSL) as one of the membrane glycoconjugates of PNH erythrocytes. Erythrocytes of all seven PNH patients showed altered expression of sialosyl GSL (gangliosides) as compared with the control erythrocytes of healthy donors. Both a sialosylparagloboside (IV6NeuAc-nLc4Cer) among four major gangliosides and some minor gangliosides in normal erythrocytes variably disappeared in erythrocytes from the peripheral blood of PNH patients. As one of the possible mechanisms of altered expression of gangliosides in PNH erythrocytes, structural analysis suggested impaired sialylation of GSL. These results suggest not only the altered metabolism of gangliosides in PNH erythrocytes, but also a metabolic disorder of membrane glycoconjugates as a new feature of PNH.

Adult↗

[A case report of lung cancer with chest wall invasion arising from a bulla wall].

A 45-year-old man with a history of pulmonary bullae complained of back pain and chest pain while playing golf. His plain chest X-ray film revealed pulmonary bullae and an 8 cm tumorous mass. Although bronchoscopic biopsy was unsuccessful, adenocarcinoma was confirmed by transcutaneous lung biopsy. Because chest wall invasion was found by CT scanning, right upper lobectomy with chest wall resection and dissection of hilar and mediastinal lymph nodes was performed (p-T3N0M0, stage IIIA, relative curative resection). The postoperative course was uneventful and no sign of recurrence is evident eight months later. It was strongly suggested by histopathological study that the chest wall invasion of poorly differentiated adenocarcinoma arose from the bulla wall. Formerly, only two non-curatively resected cases with chest wall invasion of lung cancer arising from a bulla have been reported in Japanese literature.

Adenocarcinoma↗

Monoclonal antibody to galactosylceramide: discrimination of structural difference in the ceramide moiety.

A mouse monoclonal antibody (mAb) was developed against monohexaosylceramide. This mAb differentially reacted on thin-layer chromatograms with 3 types of galactosylceramide (GalCer) obtained from bovine brain. Structural analysis of the 3 glycolipids revealed that they consisted of the same galactose and sphingosine but of apparently different fatty acids. Among the GalCers, the mAb reacted with teh two GalCers which contained alpha-hydroxy fatty acids, but not with GalCer composed of nonhydroxy fatty acids. These findings suggest that not only that the mAb discriminated the fatty acid composition in the ceramide moiety of GalCer, but also that the ceramide structure defines the immunological epitope as it is known to do for the carbohydrate moiety of glycosphingolipid.

Animals↗

Characteristic mode of action of gangliosides in selective modulation of CD4 on human T lymphocytes.

We have explored the possible mechanisms for selective modulation by gangliosides of CD4 on human T lymphocytes and subsequent re-expression of CD4. Indirect immunofluorescence staining with anti-CD4 antibodies revealed newly internalized CD4 in ganglioside-treated cells after membrane permeabilization with 0.1% saponin. Cycloheximide and other metabolic inhibitors did not alter the modulation but inhibited significantly the re-expression of CD4. These results suggest both selective modulation of CD4 by a process of endocytosis and re-expression of CD4 through de novo protein synthesis.

Antigens, Differentiation, T-Lymphocyte↗

[Chronic subdural hematoma following advanced cancer: report of three cases].

Three cases of chronic subdural hematoma (CSH) following advanced cancer are reported. Case 1. A 54-year-old male patient was referred to our clinic in a semicomatose state. Bilateral CSH was evacuated through a pair of burr holes, and consciousness was recovered. However, subependymal hemorrhage occurred at the third ventricle 6 days after the operation. Hematological examination revealed thrombocytopenia. He died 12 days after operation because of hemorrhage in the lung. Postmortem examination disclosed metastatic adenocarcinoma of unknown origin to the dura mater, lymph nodes, lung and bone marrow. Case 2. A 50-year-old male patient who was diagnosed as having gastric cancer was referred to our clinic in a state of deep coma. CT scan revealed CSH and putaminal hemorrhage at the left side. Hematological examination revealed disseminated intravascular coagulation (DIC). After the subdural hematoma was evacuated, the putaminal hematoma enlarged and hemorrhagic infarction at the left temporo-occipital lobes occurred. He died 2 days after operation. Autopsy was not carried out, but histological examination revealed poorly differentiated malignant cells in the outer membrane of the subdural hematoma. Case 3. A 53-year-old female patient who had a history of gastric cancer operated on 4 years ago was admitted to our clinic complaining of headache and vomiting. CT scan revealed bilateral subdural hematoma. Following a pair of burr-holes and irrigation of the hematoma, hemorrhage recurred alternatively at the left side on the 6th and at the right side on the 27th day after the operation. Hematological examination revealed DIC, and bone marrow puncture disclosed metastasis of the adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗