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Biomedical subjects

K Fukushima

Publications and source records attributed to K Fukushima.

At least 271 records · Page 15Linked to original sources
PubMed1996

Presence of human papillomavirus type 6f in tonsillar condyloma acuminatum and clinically normal tonsillar mucosa.

An attempt was made to detect human papillomavirus (HPV) in 8 cases of oral papilloma by Southern blot hybridization. HPV type 6 was identified in a case of tonsillar condyloma acuminatum, but neither HPV type 6 nor 11 was found in the 7 other cases of squamous papilloma. The hybridization pattern of the HPV type 6 DNA after digestion with restriction enzymes revealed that the HPV was of the 6f subtype. DNA samples isolated from the condyloma acuminatum, 3 peripheral specimens of clinically normal tonsillar mucosa, a swab sample and saliva from the male patient with this tonsillar condyloma acuminatum were examined further by polymerase chain reaction (PCR). HPV type 6 DNA was detected in the tonsillar condyloma acuminatum and the 3 specimens of clinically normal tonsillar mucosa, but no HPV type 6 DNA was detectable in the normal tonsillar mucosa by Southern blot hybridization using a whole HPV DNA probe. The presence of a small amount of HPV in clinically normal tissue detectable only by PCR suggests latent infection of peripheral tissues with HPV produced from the condyloma acuminatum. Although HPV type 6 DNA was not detectable in the swab and saliva samples of this single case, further study is necessary for the clinical application of preoperative virological diagnosis by PCR using these samples.

Adult↗
PubMed1996

A high prevalence of human papillomavirus DNA in recurrent nasal papillomas.

The prevalence of human papillomavirus (HPV) DNA in nasal papillomas was examined by polymerase chain reaction (PCR) and Southern blot hybridisation. HPV 6 DNA in one case, HPV 57 DNA in one case and HPV 16 DNA in three cases were detected amongst 12 cases of nasal papillomas that comprised three cases of fungiform exophytic papillomas and nine cases of inverted papillomas. Five cases (two exophytic and three inverted papillomas) were recurrent and four (80.0%) of these were HPV DNA-positive. The remaining seven cases were non-recurrent and only one (14.3%) was HPV DNA-positive. This difference in HPV DNA detection rates between recurrent and non-recurrent nasal papillomas was statistically significant.

Adult↗
PubMed1996

Ubiquinone systems of the genus Cladosporium and morphologically similar taxa.

The ubiquinone (coenzyme Q) systems of 14 species of Cladosporium were determined. The genus was divided into two groups based on the distribution of the major ubiquinones, Q-10 and Q-10(H2). The group containing Q-10 consisted of six species, four of which were human pathogens, whereas the group containing Q-10(H2) consisted of eight plant pathogenic and/or saprophytic species. The results presented here agree with phylogenetic and physiological studies which have shown that the human-pathogenic species of Cladosporium represent a homogeneous, cohesive group.

Cladosporium↗
PubMed1996

Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues.

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) confers specificity on the renal mineralocorticoid receptor by inactivating glucocorticoids. Mutations in this gene give rise to the syndrome of apparent mineralocorticoid excess, a congenital condition characterized by sodium retention, severe hypertension, and often by growth retardation. It is not known whether 11 beta HSD2 or another enzyme confers specificity in nonrenal sodium transporting epithelia, such as those in the sweat gland, salivary gland, and gastrointestinal tract. We previously have used the HUH23 antibody to localize 11 beta HSD2 in the human kidney, vascular smooth muscle cells, and placenta. In the present study, we have examined a range of human epithelia for the presence of 11 beta HSD2. In the skin, staining was seen in eccrine sweat glands and arterioles, whereas weak HUH23 immunostaining was observed in the epidermis. Staining was absent from sebaceous glands and hair follicles. In the parotid gland, the 11 beta HSD2 enzyme was present in striated and excretory ducts, whereas in the submandibular gland, it was found in striated and interlobular ducts. Acini, adipocytes, and associated tumor tissue did not stain with the HUH23 antibody. In the gastrointestinal tract, HUH23 stained ileal enterocytes, colonic absorptive cells, and epithelial goblet cells, whereas the rectum contained areas of staining and nonstaining absorptive cells. Gastrointestinal structures, such as the lamina propria, Peyer's patch, and goblet cells within the crypts of Lieberkuhn did not stain with the antibody. This study demonstrates the presence of 11 beta HSD2 in nonrenal sodium-transporting epithelia and describes a range of tissues affected in the syndrome of apparent mineralocorticoid excess.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

[The effect of droperidol and sevoflurane on serotonin-induced bronchoconstriction in dog].

Serotonin is a potent bronchoconstrictor, but the site of bronchoconstriction has not been determined. The present study was performed in dogs to clarify the site of bronchoconstriction induced by serotonin as well as to clarify the bronchodilating effect of droperidol and sevoflurance on the serotonin-induced bronchoconstriction by means of deflation flow-volume curve (DFVC) method, passive expiratory flow volume curve (PEFVC) method and respiratory system impedance measurement by forced oscillation method. Infusion of serotonin (60 micrograms.kg-1.min-1) induced a significant decrease in maximal expiratory flow at 10% of maximal expiratory volume (DEF10) by DFVC method and a significant increase in respiratory system impedance (Z). After droperidol (0.1 mg.kg-1) injection, DEF10 and Z returned to the control level and they remained unchanged even after the termination of serotonin infusion. Respiratory system compliance and resistance by PEFVC were unchanged by both serotonin and droperidol infusion or sevoflurane. Inhalation of 5% sevoflurane during serotonin infusion caused no significant change in DEF10. These findings indicate that serotonin-induced bronchoconstriction involves the small airway as well as the large airway. It is suggested that droperidol reversed serotonin-induced small airway constriction probably due to the antagonism of serotonin receptor in the airway. Bronchodilating effect of sevoflurane is probably limited in the small airway constricted by serotonin.

Anesthetics, Inhalation↗
PubMed1996

[Molecular biological characterization of intestinal intraepithelial lymphocytes and their receptors].

The gastrointestinal epithelial layer hosts a large population of lymphoid cells called intraepithelial lymphocytes (iIELs), and locates adjacent to the intestinal lumen and mucosal barrier. These lymphocytes are continuously exposed to orally encountered antigens via intestinal epithelial cells (iECs), and have unique phenotypical and functional features compared with T cells from other lymphoid compartments. CD3-positive T cells are major populations of iIELs and gamma delta TCR- and CD8-positive sub-populations are dominant. A close functional relationship between iIELs and iECs has been shown, and they play an important role in the immune surveillance of epithelial compartments and regulation of mucosal immune defenses to exogenous and endogenous antigens in the intestine. It is interesting that gamma delta TCR-positive iIELs regulate the generation and differentiation of iECs. The immunoregulatory functions of iIELs in the mucosal immune systems are also implicated in the oral tolerance. Basic research for the clinical trials of the oral tolerance to the treatment of autoimmune and allergic diseases recently has gegun.

Administration, Oral↗
PubMed1996

[Growth of squamous cells lung cancer between alveolar basement membrane and alveolar epithelium].

We examined patterns of growth of cancer cells in specimens of alveoli taken from 41 patients with squamous cell carcinoma (36 men and 5 women, mean age 65 years). For comparison, 8 samples from patients with small cell carcinoma (6 men and 2 women, mean age 64) and 71 samples from patients with adenocarcinoma (48 men and 23 women, mean age 62) were also studied. The samples were fixed in formalin, embedded in paraffin, and then subjected to immunostaining. Glandular structures composed of non-atypical cuboidal cells with negative p53 staining and scanty positive PCNA staining were found in 90% of the samples of squamous cell carcinoma. In small cell carcinoma, 25% of the samples had small numbers of no-atypical glandular structures. In adenocarcinoma, no non-atypical glandular structures were seen. Glandular structures were observed in the periphery of the cancerous tissue. Some of these non-atypical cells were attached to the alveolar basement membranes. We conclude that squamous cell carcinoma grows between the basement membrane and the alveolar epithelium, and leaves noncancerous epithelium with glandular structure.

Adenocarcinoma↗
PubMed1996

Retention mechanism of imidazoles in connective tissue. I. Binding to elastin.

To elucidate the retention mechanism of drugs with imidazole moiety in the connective tissue, the retention form and site of [2-14C]imidazole and 2-methyl[2-14C]imidazole were studied after intravenous administration to rats (3 micromol/kg body weight). The aorta, which is representative of the connective tissue, retained considerable radioactivity after dosing for both the imidazoles. It was observed that most of the aortic radioactivity came from the irreversibly bound fraction with elastin and that this was in close agreement with the microautoradiographic observation that showed that the retention of radioactivity occurred near the elastic fiber in the aorta. Pretreatment of rats with SKF525-A significantly increased the irreversible binding of radioactivity from the imidazoles in aorta, whereas neither phenobarbital nor 3-methylcholanthrene increased the binding. Regarding the urinary metabolite profile, the excretion of intact form significantly increased by SKF525-A pretreatment for imidazole, and an increasing tendency was also observed for 2-methylimidazole. However, no in vitro irreversible binding of imidazoles to aortic tissue was observed after incubating at physiological pH and temperature. These findings indicate that the retention of drugs with imidazole moiety in the connective tissue is largely attributable to irreversible binding between the imidazole moiety and elastin, and that the binding may be mediated through cytochrome P450-independent biotransformation.

Animals↗
PubMed1996

[Detection of HIV-1 in plasma samples using microplate hybridization after RT-PCR].

We have developed a microplate hybridization(MH) technique, which utilizes the non-isotopic method of enzyme-linked assay for detection of HIV in the amplified product after PCR. HIV RNA extracted from plasma was amplified by RT-Nested-PCR using biotinylated-inner primers of gag, pol and env regions, respectively. The PCR product was visualized by 5% polyacrylamide gel electrophoresis and ethidium bromide staining. The heat-denatured PCR product was hybridized with HIVcDNA of each region which was immobilized to a microplate. The hybridized microplate was reacted with streptavidin-conjugate peroxidase and then the optical density(O.D.) was read at 490nm. The cut off value was determined at O.D. 0.25. The results of the electrophoresis of gag, pol and env regions were all positive in 53 HIV-1 seropositive samples from Japan and the USA, and all negative in 55 HIV-1 seronegative samples. Using the MH technique, USA samples showed a higher O.D. than the Japan samples, particularly in the pol region. The results of MH technique in gag and pol regions coincided with that of electrophoresis. But, one of 27 Japanese HIV-1 seropositive samples showed O.D. of less than 0.2 in only env region. This particular sample was classified by V3 peptide-based enzyme immunoassay as subtype E, which differs from the typical subtype B of Japan and USA samples. This suggests the presence of several genotypes in HIV-1 seropositive individuals in Japan. Based on this data, the MH technique using gag, pol and env region is a simple, sensitive, safe and specific assay for detection of HIV-1 RNA in plasma, and would be useful in clinical testing.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Hypoglycemic effect and enhanced gastrointestinal absorption of insulin using new cinnamoyl-phenylalanine derivatives].

To find a new adjuvant for oral administration of Insulin (IN), we examined the gastrointestinal absorption and hypoglycemic effect of new IN-Cinnamoyl (Cin)-Phenylalanine (Phe) derivative preparations administered orally or intraduodenally to fasted normal and Streptozotocin (STZ)-diabetic animals. Selected IN.N-alpha-Chlorocinnamoyl-D-Phenylalanine (A-3989) and IN.N-alpha-Chloro-4-methyl-cinnamoyl-D-phenylalanine (A-4266) preparations among 80 of IN.Cin-Phe derivative preparations administered orally or intraduodenally promoted absorption of IN from the gastrointestinal tract resulting in significantly elevated serum IN levels and reduced serum glucose levels in fasted normal and Streptozotocin (STZ)-diabetic animals. Especially, IN.A-3989(25U.150mg/kg) and IN.A-4266(12.5U.150mg/kg) preparation administered intraduodenally represented marked enhanced IN absorption in normal mice and area under the serum IN concentration vs. time curve (AUC) showed 97.5 and 49.3 (mU.min/ml), respectively. Furthermore, A-3989 and A-4266 were found to exert inhibitory effect on IN degradation by partially purified mouse intestinal enzyme. IN.A-4266 (25U.200mg/kg) preparation administered orally before D-glucose (2g/kg) loading the significant elevation of serum IN levels and improvement of impaired glucose tolerance (IGT) in STZ-diabetic mice. Thus, these findings suggest that effective oral administration of new In.Cin-Phe derivative preparations with dosage form design, such as enteric coating form, may become feasible in diabetic patients.

Administration, Oral↗
PubMed1995

Expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on sugar chains of glycoproteins including carcinoembryonic antigens in human colon adenocarcinoma: applications of Trichosanthes japonica agglutinin I for early diagnosis.

The N-linked sugar chain structures of the carcinoembryonic antigen (CEA) produced by liver metastases of colon cancers and the normal counterpart of CEA purified from human adult feces (NFA-2) were previously determined comparatively (K. Fukushima, T. Ohkura, M. Kanai, M. Kuroki, Y. Matsuoka, A. Kobata, and K. Yamashita. Glycobiology, 5:105-115, 1995). Seventy-five % of NFA-2 contained complex type sugar chains with Gal beta 1-->3GlcNAc residues, in contrast to the sugar chains of CEA, in which over 90% of the oligosaccharides contained Gal beta 1-->4GlcNAc residues, and Sia alpha 2-->6Gal beta 1-->4GlcNAc residues were detected in 18 to 65% of the oligosaccharides. The expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on CEA molecules in sera and tissues was investigated using Trichosanthes japonica agglutinin I (TJA-I), which interacts with Sia alpha 2-->6Gal beta 1-->4 GlcNAc residues. Ten purified CEA samples bound to a TJA-I column while seven NFA-2 samples passed through the column. Various concentrations of serum CEA samples from patients with metastatic colon cancers exclusively bound to the TJA-I column, reflecting that CEA molecules exfoliated into the blood circulation comprise sugar chains with Sia alpha 2-->6Gal beta 1-->4GlcNAc residues. In histochemical studies involving biotinylated TJA-I, normal mucosa (n = 20) and benign adenomas (n = 20) were not stained, and 83% of well and moderately differentiated colon adenocarcinomas (n = 53) reacted with TJA-I, although poorly differentiated ones (n = 9) and mucinous specimens (n = 10) were negative. Because over 90% of colon adenocarcinomas can be differentiated, TJA-I staining might be applicable to the early diagnosis of colon cancers.

Adenocarcinoma↗
PubMed1995

GSH-independent denitration of the nitrate ester of a dihydropyridine derivative in rabbit hepatic cytosol.

The denitration of a dihydropyridine derivative having two nitrate ester groups, 2-nitroxypropyl 3-nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate (NND), by rabbit hepatic cytosol was investigated. Sephadex G-150 chromatography of ammonium sulfate precipitate (30-60%) from the cytosol demonstrated the presence of two distinct activities (peak I and peak II) responsible for denitration of [14C]-NND. The first peak, peak I, was observed in the presence of dithiothreitol (DTT), but not in the presence of glutathione (GSH). Moreover, the denitration activity of peak I was not inhibited by S-hexyl GSH, an inhibitor of GSH S-transferase (GST), indicating that peak I possessed no GST activity. In contrast, the denitration activity of peak II, having GST activity, required GSH and was inhibited by S-hexyl GSH. These results strongly suggest that the GSH-independent enzyme system(s), in addition to GST, is responsible for denitration of nitrate esters of NND.

Animals↗
PubMed1995

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.

Adult↗
PubMed1995

Adequacy of mucosal biopsies for evaluation of intestinal cytokine-specific mRNA. Comparative study of RT-PCR in biopsies and isolated cells from normal and inflamed intestine.

Endoscopic biopsies are being increasingly utilized to investigate cytokine profiles in normal and diseased intestine. To evaluate the adequacy of mucosal biopsies as a source of cytokine-specific mRNA, we measured their content of interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) mRNA by reverse transcription-polymerase chain reaction and compared it to that of autologous lamina propria mononuclear cells in control and inflammatory bowel disease-involved specimens. High-quality total RNA was recovered more consistently from cell isolates than from biopsies. Interleukin-1 beta mRNA was reliably detected in both cell and biopsy samples, whereas IL-2 mRNA was measurable in all lamina propria cells but not always in biopsies. Compared to controls, levels of IL-1 beta were significantly elevated in Crohn's disease and ulcerative colitis cells and biopsies, and a weak but significant correlation existed between values derived from the two sources. In contrast, only ulcerative colitis cell isolates but not biopsies contained significantly reduced concentrations of IL-2 mRNA compared to those of control and Crohn's disease samples, and no correlation was found between cell and biopsy contents. Widely different levels of cytokine-specific mRNA were present in closely adjacent biopsies, particularly for IL-2. These results suggest that mucosal biopsies are suitable to assess some but not all cytokine-specific mRNA due to variation in RNA recovery, intrinsic level of cytokine gene expression, and substantial variability of cytokine transcripts.

Adolescent↗
PubMed1995

Vestibular integrators in the oculomotor system.

The interstitial nucleus of Cajal (INC) and the nucleus prepositus hypoglossi (nph) are key elements in the vertical and horizontal oculomotor neural integrators, respectively. In this article, we attempt to develop possible circuits for these vestibular integrators by synthesizing recent information on the properties and connections of neurons involved in the integration process. We also examine how the cerebellar flocculus could play a role in the vertical integrator and vestibulo-ocular reflex (VOR) as well as in the modulation and plasticity of the VOR. We suggest that the circuitry for the vertical integrator involves the cerebellar flocculus in addition to the already proposed circuits distributed between the INC and the vestibular nuclei. The horizontal vestibular integrator is also distributed and seems to be characterized by functional compartmentalization. Both integrators play a wider role than simply transforming velocity-coded signals into position commands and may be pivotal in the short- and long-term modulation of the various oculomotor subsystems.

Animals↗