Blockade of cutaneous nerve-evoked responses by GR71251 in the isolated spinal cord preparation of newborn rat.
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Animals↗
Biomedical subjects
K Yoshioka
Publications and source records attributed to K Yoshioka.
Substance P-evoked release of amino acid transmitters from the newborn rat spinal cord.
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Amino Acids↗
Brachydactyly type A-4 (Temtamy type) with short stature in a Japanese girl and her mother.
We report on a Japanese girl and her mother with brachydactyly. Their 2nd and 5th middle phalanges were short and the latter was fused with the distal phalanx in one of the patients. Length and shape of proximal and distal phalanges as well as metacarpals seemed normal. These findings are consistent with brachydactyly type 4-A, which is a rare subtype and has not been adequately documented. Short stature was reported only in some cases of brachydactyly type A-1, A-6, C, and E, but not in the other subtypes. Our patients with type A-4 brachydactyly also had short stature.
Abnormalities, Multiple↗
Glomerular-basement-membrane antibody and extracorporeal shock wave lithotripsy.
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Adult↗
Retraction of cultured endothelial cell monolayer by human breast cancer cells, MCF-7.
A human breast cancer cell line (MCF-7), when sealed on confluent bovine pulmonary aortic endothelial cell (CPAE) monolayers, induced morphological changes (retraction) in CPAE cells. The area of retraction depended on the incubation time and the number of MCF-7 cells, suggesting that MCF-7 cells had the capacity to retract CPAE cells. This capacity was reduced by 60% by pretreatment of MCF-7 cells with 17 beta-estradiol (E) and progesterone (Pg). The extent of retraction was not affected by the addition of various protease inhibitors. CPAE retraction was induced also by adding conditioned medium (CM) from the culture of MCF-7 cells. Considerably less activity was detected in the CM obtained from MCF-7 cells cultured in the presence of E and Pg. The retraction was reversed in 24 h by culturing the monolayer in fresh medium without CM and was not induced by trypsin treatment of the CM.
Breast Neoplasms↗
Orphan peak analysis: a novel method for detection of point mutations using an automated fluorescence DNA sequencer.
Automated DNA sequencers draw the four-base profiles of a sample with four different colors, but it is also possible to draw the profiles of a base-specific reaction of four different samples with four colors. PCR-amplified DNAs from four individuals were subjected to a single base-specific sequencing reaction and the products were applied to a set of four lanes of an automated DNA sequencer. A base substitution in an individual was clearly identified as an individual-specific peak with a color specific for the individual. In this way, we analyzed more than 50 individuals and identified several polymorphic base substitutions. The sensitivity of this method was high enough to allow detection of the mutation/polymorphism even if samples from several individuals were applied to one lane. Thus, our method is applicable to screening of a large number of samples in an automated manner.
Amyloid beta-Protein Precursor↗
Comparison of envelope and precore/core variants of hepatitis B virus (HBV) during chronic HBV infection.
We analyzed entire pre-C/C and pre-S/S coding genes of hepatitis B virus (HBV) in serial serum samples from four chronic HBV carriers with 4-5 years of follow-up. Two patients with chronic active hepatitis became seronegative for HB e antigen (HBeAg), but the hepatitis did not subside, while the other two were persistent asymptomatic carriers with normal aminotransferase values. DNAs amplified by PCR were cloned and sequenced (subtype adr). After HBeAg became negative, one patient had 96-183 bp deletions in 4/6 clones for C gene. In addition, both patients had 129-183 bp deletions in 3/6 and 2/5 clones for pre-S1 gene, respectively. Divergence rate of deduced amino acid for both pre-C/C and pre-S/S regions from the adr subtype was significantly higher in patients with chronic hepatitis than in asymptomatic carriers. Furthermore, the divergence rate for pre-S/S region was usually greater in asymptomatic carriers as well as chronic hepatitis patients compared with that for pre-C/C region. However, no significant difference was found in the rate of amino acid divergence for the entire HBV genes between the serial samples in all patients studied here. These results suggest that active hepatitis induces variation of HBV gene and defective virus is often selected along with the disappearance of HBeAg. In addition, the fact that patients with active liver disease possess greater numbers of mutant clones than asymptomatic carriers suggests that viral mutants are being immune-selected.
Adult↗
Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo.
To substantiate and extend the quasispecies model of hepatitis C virus (HCV), we made a pairwise comparison in the nucleotide and deduced amino acid sequences for multiple recombinant clones of the E2/NS1 region, which derived from each blood sample taken from five patients of subtype II or subtype III infection at different stages. Sequence heterogeneity among the clones was generally high. The heterogeneity, however, changed temporally and appeared to be significantly lowered after interferon therapy. The temporal fluctuation involved selection of particular amino acids at particular positions, which had represented only a minor fraction or had been absent in the previous clones. Evolution of defective viruses was featured by most of the cases, the proportion of which also fluctuated temporally and was extremely high at a certain stage in one of the patients. A comparison was also made among the clones from different stages of each patient and revealed highly divergent clones. An extreme case of subtype III infection showed sequence differences well beyond those among chronologically and geographically different isolates of subtype I or subtype II, which were defined by the same calculation of available sequence data. These features of HCV genome suggest that the virus could circulate as an extremely heterogeneous population including defective viruses and that this heterogeneity lends itself to selection pressures including interferon therapy and host immune response. Our results also indicate an absolute need of population based approach in HCV genetics.
Aged↗
Immunotactoid glomerulopathy in a child with Down syndrome.
A 9-year-old girl with Down (21-trisomy) syndrome was found to have proteinuria and microscopic haematuria at age 6 years. Proteinuria gradually increased during the next 3 years, although blood pressure and renal function remained normal. The patient exhibited no underlying systemic diseases, monoclonal gammopathy, cryoglobulinaemia or histological evidence of plasmacytoma. A percutaneous renal biopsy revealed immunotactoid glomerulopathy (fibrillary glomerulonephritis) characterized by thickening of the glomerular basement membrane, diffuse mesangial expansion and various-sized acid-Schiff-positive nodules that were intensely positive for IgG, light chains (kappa and lambda) and complement components (C3, C4, C1q) along the glomerular capillaries in the mesangium. Congo red dye and amyloid thioflavine T staining were negative. Fibrils (15-17 nm in diameter--larger than amyloid fibrils) were present in the mesangial area and within the glomerular basement membrane. We are not aware of a previous report of immunotactoid glomerulopathy and a patient with chromosomal abnormalities.
Child↗
Immunohistochemical localization of C3d fragment of complement and S-protein (vitronectin) in normal and diseased human kidneys: association with the C5b-9 complex and vitronectin receptor.
The localization of C3d, a fragment produced by C3 activation and S-protein (vitronectin), a regulatory factor of C5b-9, was studied immunohistochemically in normal human kidney and renal biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that C3d was present along the glomerular basement membrane (GBM), tubular basement membrane (TBM) and arterioles, and that S-protein was present in the GBM, mesangium, TBM, and arterioles. Immunoelectron microscopy of isolated basement membranes showed that C3d was localized exclusively on the epithelial side of the GBM, and that S-protein was present along both the epithelial and endothelial sides. In nephritic tissues, glomerular staining of C3d, C5b-9, and S-protein was increased when compared with that in normal tissues. S-protein, frequently co-localized with C3d and C5b-9 neoantigen, was intensely positive in the immune deposits of glomerular capillaries and the mesangial area, overlapping the background staining of GBM and mesangial matrix. S-protein and its receptor were occasionally co-localized in the glomeruli. These findings indicate that C3d and S-protein are normally present in the glomeruli. Co-staining of C3d, C5b-9 neoantigen, and S-protein within the immune deposits of nephritic kidneys suggests in situ binding of S-protein to locally-formed C5b-9 complex, or merely co-distribution of S-protein with the complex, rather than trapping of large molecular SC5b-9 complex from the circulation.
Complement C3d↗
Interleukin 6 production by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection and primary biliary cirrhosis.
IL-6 production by peripheral blood mononuclear cells (PBMC) was studied in patients with chronic hepatitis B virus (HBV) infection and primary biliary cirrhosis (PBC) using the ELISA method. Spontaneous production of IL-6 was significantly increased in patients with HBeAg+ chronic hepatitis (CH). The cultures stimulated with lipopolysaccharide and lectin-free interleukin-2 (IL-2) showed enhanced IL-6 production both in controls and all patient groups compared with culture without any stimulation. IL-6 production in response to IL-2 was higher in patients with HBeAg+ CH and PBC than in controls. In PBMC with increased IL-6 production, monocyte function was increased in patients with HBeAg+ CH and PBC, while B cells from PBC showed elevated response to Staphylococcus aureus Cowan 1. IL-6 production in the presence of HBeAg was greater in anti-HBe+ patients than in HBeAg+ ones. These results suggest that IL-6 response is involved in the immune response in patients with chronic liver disease.
Adult↗
Cytotoxic T lymphocyte activity to hepatitis B virus DNA-transfected HepG2 cells in patients with chronic hepatitis B.
Cytotoxic T lymphocyte (CTL) activity for hepatitis B virus (HBV) DNA-transfected HepG2 cells (designated HB3-5), which secrete HBsAg, HBeAg and HBV particles, was investigated in 31 patients with chronic HBV infection (18 chronic hepatitis and 13 asymptomatic carriers). 51Cr-labeled HB3-5 with A2 as a major HLA class I antigen served as target cells and T cells from peripheral blood mononuclear cells as effector cells. The CTL activity was measured by a 51Cr release assay. Patients were divided into two groups, the A2 group bearing HLA-A2 and the non-A2 group not bearing HLA-A2. Chronic hepatitis patients in the A2 group showed increased HBV Ag-specific cytotoxicity compared with that seen in the non-A2 group (5.2 +/- 3.1% vs. 0.9 +/- 1.4%; means +/- SD, P < 0.01). In the A2 group with chronic hepatitis, the cytotoxicity was greater in anti-HBe positive patients than in HBeAg positive patients (8.6 +/- 1.9% vs. 3.4 +/- 2.0%, P < 0.01), and asymptomatic carriers showed less cytotoxicity (0.35 +/- 0.31%, P < 0.001) compared with chronic hepatitis patients. In the non-A2 group, HBV Ag-specific CTL activity was negligible in most patients and thus no differences were found among all patient groups. The HBV Ag-specific cytotoxicity was inhibited by antibodies to CD3, HLA class I and hepatitis B nucleocapsid antigens. Removal of CD8+ cells also resulted in marked decrease in the cytotoxicity. These findings indicate that HBV Ag-specific cytotoxicity reflects liver cell damage and HBeAg/anti-HBe status. Furthermore, our assay system appears to be useful to assess CTL response in patients with chronic HBV infection.
Adult↗
Insulin-dependent diabetes mellitus associated with Graves' disease and idiopathic hypoparathyroidism.
We report a case of 26-year-old woman with Graves' disease and idiopathic hypoparathyroidism diagnosed at 11 years of age, who subsequently developed insulin-dependent diabetes mellitus (IDDM) at 17 years of age. Treatment with antithyroid agents had failed to control her Graves' disease and her IDDM was unmanageable despite insulin therapy. Surgical intervention was carried out, resulting in an improvement of both her hyperthyroidism and IDDM. This case is the first report of polyglandular autoimmune (PGA) syndrome, presenting the association of IDDM, Graves' disease and idiopathic hypoparathyroidism.
Adult↗
A pilot study of ribavirin and interferon beta for the treatment of chronic hepatitis C.
BACKGROUND: Chronic hepatitis C is a common and often progressive liver disease for which interferon alfa therapy widely spreads, but the beneficial response is frequently transient. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action, and we investigated the efficacy of it in patients with chronic active hepatitis C. METHODS: We conducted a pilot study of oral ribavirin in patients with chronic active hepatitis C. Twenty-seven patients with hepatitis C virus RNA were randomly assigned to receive either 0.8-1.0 g of ribavirin daily or 3 MU of interferon beta three times weekly or combination of the two for 24 weeks. RESULTS: Ribavirin was tolerated well, and all completed the treatment schedule. Ribavirin decreased aminotransferase levels in all instances, and the mean value at termination decreased to half of the baseline level (P < 0.01), but the enzyme level increased after cessation of therapy in most cases. Ribavirin suppressed amounts of hepatitis C virus RNA in 4 of 9 patients, and 1 became negative during follow-up. Interferon alone (P < 0.05) or with ribavirin (P < 0.01) significantly decreased the viral population, resulting in sustained loss of viremia with normal enzyme levels in 2 of 9 and 3 of 9 patients, respectively, in each therapy during follow-up. CONCLUSIONS: These results indicate that ribavirin has a beneficial effect in some patients with chronic hepatitis C, although the antiviral effect is less than interferon beta. Large-scale trials are needed to determine whether the combination of interferon and ribavirin is of more benefit than interferon alone.
Adult↗
Developmental studies of dystrophin-positive fibers in mdx, and DRP localization.
Dystrophin positive fibers (DPFs) were observed in about 1% of the total muscle fibers in 1-year-old mice. Some of these fibers were found to have positive staining with all six antibodies, while others showed a negative reaction with specific antibodies. These results suggest that the most likely mechanism giving rise to these DPFs is a second site mutation which prepares in-frame deletion. A study of the frequency of DPF during development showed single and scattered DPFs in younger mice, which gradually increased in number and began to form small groups with age. DRP was observed constantly on the neuromuscular junctions in both control and mdx muscle, and surface membrane of immature muscle fibers such as regenerating fibers in mdx and newborn muscle during 2 weeks of age in control and mdx.
Aging↗
Dystrophin isoforms expressed in the mouse retina.
The dystrophin gene is expressed in various tissues of the mouse. Previous immunohistochemical studies suggested the existence of dystrophin protein in the outer plexiform layer of the retina. We analyzed mRNAs from the retina and other tissues of mice and detected the dystrophin transcripts (DT) with the use of the reverse transcription and polymerase chain reaction (RT-PCR) method. The 5' sequences, corresponding to the first exon, of DT in the retina was mainly the brain type, whereas in the 3' region of DT that corresponds to the C-terminal domain of dystrophin, some additional RT-PCR products were detected. Base sequences in three of them showed homology to those for previously reported human dystrophin isoforms. The DT variations in mice were identical between the retina and the brain. It was thus concluded that dystrophin really expresses in the mouse retina and most of the retinal dystrophin proteins belong to the brain type isoform.
Animals↗
Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.
Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.
Animals↗
Hepatitis C virus infection in children with hemophilia: characterization of antibody response to four different antigens and relationship of antibody response, viremia, and hepatic dysfunction.
We studied hepatitis C virus (HCV) infection in children with hemophilia by characterizing the antibody responses to four different HCV antigens and investigating the relationship of the antibody response to viremia and hepatic dysfunction. Three antigens (core, nonstructural (NS) 3, and NS5) were expressed in Escherichia coli transfected with plasmids that contained fragments of the putative core and of the NS3 and NS5 regions of the HCV genome, respectively. Antibody responses to these three antigens and the commercially available C100 antigen were detected by enzyme-linked immunosorbent assay. In 45 children with hemophilia, the percentage of children with seropositivity for C100, core, NS3, and NS5 protein in one or more specimens was 82%, 91%, 91%, and 89%, respectively. The time course of changes in the antibody response to the four antigens was determined by using sera obtained from 44 of the 45 patients at intervals of 1 to 4 years. Antibodies to the core and NS3 antigens appeared earlier and persisted longer than those to C100 and NS5 after HCV infection. The relationship of antibody response to viremia and hepatic dysfunction was investigated in 27 children by using the polymerase chain reaction assay. Five children whose tests results were negative for all four antigens did not have viremia or hepatic dysfunction; 13 of the 16 children with positive results for the four antigens had both viremia and hepatic dysfunction. Five of the six children whose serum had the core and NS3 antibodies but not either C100 or NS5, or both, had viremia, and three of them also had hepatic dysfunction. These results suggest that detection of antibodies to the core and NS3 antigens is useful for the serologic diagnosis of HCV infection and that both antibodies are more related to viremia than are the antibodies to C100 and NS5. In addition, viremia is strongly associated with hepatic dysfunction.
Adolescent↗