Biomedical subjects

S Chiba

Publications and source records attributed to S Chiba.

At least 127 records · Page 7Linked to original sources

PubMed2000

Immunogene therapy against mouse leukemia using B7 molecules.

B7 costimulatory molecules play an important role in T-cell activation. It is well known that tumor cells that express B7 molecules can elicit antitumor immunity, but little is known regarding which B7 molecule, B7-1 (CD80) or B7-2 (CD86), can do so more efficiently. To address this issue, we have introduced B7-1 or B7-2 into 8709 cells, a radiation-induced mouse myelocytic leukemic cell line, and have compared their potentials regarding the induction of antitumor immunity. Either B7-1- or B7-2-transduced monoclonal sublines, 8709/B7-1 or 8709/B7-2, respectively, diminished tumorigenicity in syngeneic C3H mice. Some reports have indicated that B7-1 is superior to B7-2 in the induction of antitumor immunity. Contrary to these results, the 8709/B7-2 lines are superior to the 8709/B7-1 lines in their capacity to induce antitumor immunity. In vivo depletion of lymphocyte subsets demonstrated that both CD4+ and CD8+ T cells were indispensable for B7-1- or B7-2-dependent antitumor immunity, whereas natural killer cells were not. These results suggest that in some circumstances, B7-2 molecule is more effective than B7-1 molecule in eliciting antitumor immunity.

Animals↗

PubMed2000

Generation of HLA-DRB1*1501-restricted p190 minor bcr-abl (e1a2)-specific CD4+ T lymphocytes.

A small population of cells in acute lymphoblastic leukaemia is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster lesion (bcr) on chromosome 22, t(9; 22)(q34; q11) (e1a2). Theoretically, the junction-spanning sequences of oncogene fusion proteins might be ideal targets for immunotherapy because these are not present in normal cells. In this study, we show for the first time that in vitro immunization with a 17-mer e1a2 peptide representing the p190 minor bcr-abl fusion protein resulted in HLA-DRB1*1501-restricted peptide-specific proliferative CD4+ T lymphocytes, using peptide-pulsed monocyte-derived dendritic cells as the antigen-presenting cells.

CD4-Positive T-Lymphocytes↗

PubMed2000

The lymphoproliferative response to enzymatically digested gelatin in subjects with gelatin hypersensitivity.

BACKGROUND: This study was designed to evaluate the immunogenic characteristics of enzymatically digested gelatin, 'FreAlagin', employing the lymphoproliferative response in subjects with gelatin hypersensitivity. Our purpose was to assess the response of primed lymphocytes to the newly developed FreAlagin and compare it to the response to conventional gelatin. METHODS: A gelatin-specific lymphocyte proliferation test (LPT) was performed in 110 children with adverse reactions to gelatin-containing vaccines, who showed positive gelatin-specific cell-mediated immunity and were thus diagnosed as having gelatin hypersensitivity. Gelatin-specific IgE was measured in all subjects. The antigenic activity of FreAlagin to lymphocytes was compared with that of conventional bovine gelatin. Positive and negative control specimens were obtained from the patients with anaphylaxis and from subjects inoculated with gelatin-free vaccine who showed no adverse reactions in order to establish the fluorometric ELISA system to determine IgE antibody to gelatin and LPT. RESULTS: The lymphocyte activity against FreAlagin was much less than that to Wako gelatin and more than half of the subjects who reacted positively to Wako gelatin had a negative LPT to FreAlagin. Although 47% of the subjects had positive LPTs to FreAlagin, all but two still had lower SIs to FreAlagin compared with Wako gelatin. CONCLUSION: We conclude that the antigenic activity of FreAlagin as measured by the cell-mediated immune response is significantly less than that of conventional bovine gelatin. However, it is still necessary to perform clinical trials to show a reduced or absent clinical reactivity to FreAlagin in sensitized patients to conventional gelatin.

Animals↗

PubMed2000

Presynaptic inhibitory actions of lignocaine in canine isolated, blood-perfused atrial preparations.

1. Cardiac effects of lignocaine on sinoatrial nodal pacemaker activity and atrial contractility were investigated in five canine isolated, blood-perfused right atria that were perfused with heparinized blood from support dogs. The effects of lignocaine on responses to intracardiac nerve stimulation and administered acetylcholine and noradrenaline were also examined. 2. Lignocaine was injected into the support dog intravenously or administered selectively to the sinus node artery of the isolated atrium. At doses that did not produce significant depressor action (0.3, 1.0 and 3.0 mg/kg), lignocaine produced no significant changes in heart rate. A large dose of 10 mg/kg lignocaine caused significant depressor effects and slight bradycardia. Direct administration of lignocaine (0.3, 1.0, 3.0, 10.0 and 30.0 mumol) into the sinus node artery of the isolated atrium consistently caused slight negative chronotropic and rather marked negative inotropic effects. 3. After treatment with a relatively large dose of lignocaine, electrical stimulation-induced negative chronotropic and inotropic responses were significantly inhibited in a dose-related manner, but positive chronotropic and inotropic responses were slightly depressed only at an extremely high dose of lignocaine (10.0 mumol). 4. Noradrenaline-induced positive chronotropic and inotropic effects were not modified by any doses of lignocaine used (0.3, 1.0, 3.0 and 10.0 mumol). Acetylcholine-induced negative chronotropic and inotropic effects were slightly, but significantly, depressed by 10 mumol lignocaine. 5. These results suggest that a relatively large dose of lignocaine has a dominant presynaptic inhibitory action, particularly on the parasympathetic component.

Anesthetics, Local↗

PubMed2000

Effect of temperature on responses of dog isolated lingual and mesenteric arteries to vasoactive substances.

1. The effects of temperature on submaximal vasoconstriction to an intraluminal administration of noradrenaline (NA), phenylephrine, tyramine and KCl were investigated in canine isolated and perfused lingual and mesenteric arteries, using the cannula-inserting method. 2. In lingual arteries, cooling (from 37 to 27 degrees C) caused significant depression of vasoconstriction to the four vasoactive substances used. Rewarming (to 37 degrees C) induced a significant augmentation of constriction by NA, phenylephrine and KCl, but not tyramine. 3. In mesenteric arteries, cooling depressed tyramine- and KCl-induced constrictions, but had no effect on NA- and phenylephrine-induced vasoconstriction. Only in the case of KCl-induced constrictions did rewarming induce a potentiation of the vasoconstrictor response. 4. We conclude that: (i) cooling induces a depression of voltage-dependent Ca2+ channels and rewarming may induce a potentiation of Ca2+ channels in both arteries; (ii) alpha1-adrenoceptor-operated Ca2+ channels are depressed by cooling in lingual arteries but not in mesenteric arteries; and (iii) cooling may induce an attenuation of the re-uptake function in sympathetic nerve terminals in both arteries and this attenuation may be not rapidly restored by acute rewarming.

Adrenergic alpha-Agonists↗

PubMed2000

Sleep architectures of obstructive sleep apnea syndrome in the young child.

The sleep architectures of obstructive sleep apnea syndrome (OSAS) in the young child (child-OSAS, n = 17; mean age: 5.9+/-2.7 years; male:female 14:3) were compared with that of OSAS in the adult (n = 19; mean age: 44.7+/-10.7 years; male:female 18:1) and that of primary snoring in the child (n = 5; mean age: 7.0+/-2.4 years; male:female 5:0). Child-OSAS and OSAS in the adult had the same severity in oxygen desaturation. Child-OSAS showed lower Apnea-Hypopnea Index compared with OSAS in the adult. Sleep continuity in child-OSAS was not impaired compared with OSAS in the adult. Sleep fragmentation in child-OSAS was not so remarkable. The quantity of slow wave sleep in child-OSAS was similar to that of primary snoring in the child. Both profiles of sleep architectures showed nearly the same pattern.

Cerebral Cortex↗

PubMed2000

Recent increase in the frequency of infant measles in Japan.

BACKGROUND: Because there has been no major outbreak of measles in Japan during the last decade, subclinical boosting of pre-existing immunity by exposure to epidemic measles is unlikely to have occurred. Consequently, the measles immunity of mothers of this generation is less well developed and they provide less effective passive immunity to their infants. An increase in the frequency of infant measles is therefore probable. METHOD AND RESULTS: A retrospective review was undertaken of the clinical records of all measles cases that occurred in the last 3 years in eight hospitals and two out-patient clinics in Hokkaido. Of 541 recorded cases, 96 (17.7%) were infants and of these, 66 patients (68.8%) were over 9 months of age. Only 20 children had received measles vaccination. CONCLUSION: There has been a recent increase in the frequency of infant measles, suggesting an increased population of infants susceptible to measles before the age of 1. Of the older patients, 95% had not been vaccinated against measles. Increasing the rate of measles vaccination may help suppress future measles outbreaks and assist in protecting infants until they pass their first birthday.

Adolescent↗

PubMed2000

Sapporo virus: history and recent findings.

Morphologically distinct caliciviruses of human origin were first found in stools of children with gastroenteritis in 1976. Sapporo virus, or human calicivirus Sapporo, with typical surface morphology was first detected during a gastroenteritis outbreak in a home for infants in Sapporo, Japan, in 1977. Since then, morphologically and antigenically identical virus has been detected frequently in the same institution in association with outbreaks of gastroenteritis. Sapporo virus is widely distributed worldwide, as evidenced by the appearance of antigenically or genetically similar viruses and seroepidemiologic findings. Sapporo virus plays an important role in outbreaks of infantile gastroenteritis and is less important in foodborne outbreaks. Sapporo virus has been approved as the type species of the genus "Sapporo-like viruses in the family Caliciviridae. The history of and recent findings, as obtained by newly developed techniques, about Sapporo viruses are presented.

Caliciviridae↗

PubMed2000

Rapid mutation screening of phenylketonuria by polymerase chain reaction-linked restriction enzyme assay and direct sequence of the phenylalanine hydroxylase gene: clinical application in northern Japan and northern China.

We describe a simple and technically feasible method for mutation screening of the phenylalanine hydroxylase (PAH) gene and its application to Japanese and Chinese patients with hyperphenylalaninemia. The strategy is based on the identification of a nucleotide substitution by restriction enzyme analysis, coupled with PCR and direct sequencing of exon 7 of the PAH gene. Because the detection of various mutations can proceed simultaneously using the same technique, it is quite rapid and reproducible, making it possible to perform effective molecular diagnosis and carrier screening in most laboratories. Using this procedure, we found that the most common molecular defects were R413P in Hokkaido, Japan (35 %) and R243Q in Heilongjiang, China (50%). R111X, IVS4nt-1, and five mutations in exon 7 (R241C, R243Q, R252W, A259T, and S273P) accounted for 55% of phenylketonuria (PKU) alleles in Hokkaido. In Heilongjiang, the R111X, Y356X, and R408W mutations accounted for 35% of PKU alleles. Clinically, homozygotes or compound heterozygotes of null alleles, which express nonfunctional enzyme activity, were all associated with classic PKU. On the other hand, patients heterozygous for the R241C allele had a benign phenotype of mild hyperphenylalaninemia. The DNA diagnosis in early infancy can predict various PKU phenotypes, and can prove useful in decision-making concerning dietary therapy.

Adolescent↗

PubMed2000

Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis.

FtsH-mediated proteolysis against membrane proteins is processive, and presumably involves dislocation of the substrate into the cytosol where the enzymatic domains of FtsH reside. To study how such a mode of proteolysis is initiated, we manipulated N-terminal cytosolic tails of three membrane proteins. YccA, a natural substrate of FtsH was found to require the N-terminal tail of 20 amino acid residues or longer to be degraded by FtsH in vivo. Three unrelated sequences of this segment conferred the FtsH sensitivity to YccA. An artificially constructed TM9-PhoA protein, derived from SecY, as well as the SecE protein, were sensitized to FtsH by addition of extra amino acid sequences to their N-terminal cytosolic tails. Thus, FtsH recognizes a cytosolic region of sufficient length (approximately 20 amino acids) to initiate the processive proteolysis against membrane proteins. Such a region is typically at the N-terminus and can be diverse in amino acid sequences.

Amino Acid Sequence↗

PubMed2000

Simultaneous development of a pineal tumor and an intradural spinal mass during remission of acute lymphocytic leukemia.

A small percentage of children with acute lymphocytic leukemia experience relapse in the central nervous system in spite of prophylaxis. Diffuse leptomeningeal infiltration is common but an intracranial leukemic mass or spinal cord involvement is a rare manifestation. We report a child with acute lymphocytic leukemia who simultaneously developed a pineal tumor and an intradural spinal cord mass as her first relapse. She was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation. She remains in continuous complete remission for more than 5 years without further evidence of neurological sequelae.

Child, Preschool↗

PubMed2000

Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome.

The predictable chronological sequence of pathological events in Down syndrome (DS) provides the opportunity to rigorously investigate the relationship between oxidative stress and amyloid-beta (Abeta) deposition. In this study, we report a marked accumulation of oxidized nucleic acid, 8-hydroxyguanosine (8OHG), and oxidized protein, nitrotyrosine, in the cytoplasm of cerebral neurons in DS with the levels of nucleic acid and protein oxidation paralleling each other. Relative density measurements of neuronal 8OHG immunoreactivity showed that there was a significant increase (p < 0.02) in DS (n = 22, ages 0.3-65 yr) compared with age-matched controls (n = 10, ages 0.3-64 yr). As a function of age, 8OHG immunoreactivity increased significantly in the teens and twenties (p < 0.04), while Abeta burden only increased after age 30 (p < 0.0001). In 9 cases of DS bearing Abeta deposition, the extent of deposits of Abeta ending at amino acid 42 (Abeta42) was actually associated with a decrease in relative 8OHG (r = -0.79, p < 0.015) while Abeta40 was not. These findings suggest that in brains of patients with DS, increased levels of oxidative damage occur prior to the onset of Abeta deposition.

Adolescent↗

PubMed2000

Differential effects of omega-conotoxin GVIA, tetrodotoxin and prolonged cold storage on purinergic and adrenergic transmission in isolated canine splenic artery.

UNLABELLED: Double-peaked vasoconstrictions (biphases of vasoconstrictions) were readily induced in the conditions of 30 s trains of pulses at 1 Hz in the isolated, perfused canine splenic artery. P2X purinoceptors have previously been shown to be involved mainfy in the first-peaked response and alpha1-adrenoceptors mostly in the second. The treatment with 10 nM omega-conotoxin GVIA (omega-CTX) produced a parallel inhibitory effect on the first- and second-peaked vasoconstrictor responses to nerve stimulation. A submaximal concentration of tetrodotoxin (TTX) (3 nM) did not affect the first peak of constriction, but strongly inhibited the second peak, although a larger dose of TTX (30 nM) abolished either the first- or second-peaked response. On the other hand, after cold storage at 4 degrees C for 7 days, the first-peaked vasoconstriction markedly decreased, whereas the second-peaked response was not significantly modified. IN CONCLUSION: (1) omega-CTX-sensitive calcium channels may produce a parallel modulation of purinergic and adrenergic components of sympathetic cotransmission; (2) TTX-sensitive sodium channels may have a more important role in controlling the adrenergic rather than purinergic transmission; and (3) the function of purinergic transmission of sympathetic nerve might be affected more strongly than that of adrenergic transmission in the cold-stored canine splenic artery.

Adenosine Triphosphate↗

PubMed2000

The role of osteopontin in the development of granulomatous lesions in lung.

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression may be a common factor involved in formation of granulomas of various origin.

Adenoviridae↗

PubMed2000

Evaluation of nine sets of PCR primers in the RNA dependent RNA polymerase region for detection and differentiation of members of the family Caliciviridae, Norwalk virus and Sapporo virus.

Norwalk virus and Sapporo virus were approved as type species of the genus "Norwalk-like viruses" and the genus "Sapporo-like viruses," respectively, in the family Caliciviridae. A total of 116 stool specimens containing Norwalk virus (NV) or Sapporo virus (SV) were tested by RT-PCR and Southern hybridization to evaluate nine sets of PCR primers and seven internal oligonucleotide probes in the RNA dependent RNA polymerase region of NV and SV for detection and differentiation of viruses in the NV and SV. Fifty-five stool samples were collected from 11 outbreaks of NV and/or SV gastroenteritis in an infant home, where residents were infants under 2 years of age, in Sapporo, Japan. Sixty specimens were obtained in Sapporo from sporadic cases in children, mainly under 6 years of age, of acute gastroenteritis due to small round structured viruses detected by EM. There is no single primer pair to detect all NV and SV, and at least three primer pairs, G1 set, G2 set and Sapp35/Sapp36, are required to detect viruses in the NV and SV clades. Many NV and SV strains were successfully classified into one of the NV/genogroup I, NV/genogroup II and SV by single-round RT-PCR and Southern hybridization. The new detection method for SV reported in this study combined with those for NV previously reported may elucidate the importance of Norwalk virus and Sapporo virus as a cause of viral gastroenteritis in all age groups in the world.

Blotting, Southern↗

PubMed2000

Analysis of Chlamydia trachomatis serovars in endocervical specimens derived from pregnant Japanese women.

The polymerase chain reaction (PCR) method has been employed to amplify a chlamydial genome encoding four variable segments of the major outer membrane protein and genotyping of different Chlamydia trachomatis serovars was successfully achieved by means of restriction fragment length polymorphism (RFLP) analysis and sequencing of amplified DNA. These methods were applied to identify the serotypes of C. trachomatis in endocervical specimens obtained from asymptomatic pregnant Japanese women at 28-30 weeks of gestation. Among the 218 specimens, 207 were serotyped 43 (19.3%) as serovar D, 53 (24.3%) as E, 24 (11.0%) as F, 39 (17.9%) as G, 15 (6. 9%) as H, 15 (6.9%) as I, five (2.3%) as J, nine (4.1%) as K and four (1.8%) as mixed. Among the 11 unclassified strains by RFLP, six (2.8%) were identified as serovar B variants and five (2.3%) were identified as D/IC-Cal-8. It was suggested that variants of endemic trachoma serovars also have affinity for the urogenital tract of Japanese pregnant women.

Amino Acid Sequence↗

PubMed2000

Real-time automated PCR for early diagnosis and monitoring of cytomegalovirus infection after bone marrow transplantation.

The purpose of this study was to assess the usefulness of real-time automated PCR as a quantitative, highly reproducible, and sensitive method to detect cytomegalovirus (CMV) DNA in blood specimens. Intra- and interassay precision rates were 0.89% (small number of copies [L]), 1.43% (middle number of copies [M]), and 1.12% (high number of copies [H]), and 4.46% (L), 1.51% (M), and 2.28% (H), respectively. The linearity of this assay was obtained between 10 and 10(7) copies/well, with a minimum detection limit of 20 copies/well. Specimens from 55 of 70 healthy subjects were found to be positive for CMV antibody, but CMV DNA was not detected in any of them. In the qualitative assessment of each specimen, the results of the CMV antigenemia assay and those of the real-time PCR assay agreed in 80% (plasma specimens), 79% (all nucleated cells), and 86% (blood) of the cases examined. For eight patients diagnosed as having CMV infection or disease, no sample was positive in the antigenemia assay earlier than in the real-time PCR assay. Furthermore, the results of this assay could be obtained within 8 h. We concluded that the real-time PCR assay is useful for rapid diagnosis of CMV infection and monitoring of clinical courses.

Adolescent↗

PubMed2000

Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2.

Delta1, Jagged1, and Jagged2, commonly designated Delta/Serrate/LAG-2 (DSL) proteins, are known to be ligands for Notch1. However, it has been less understood whether they are ligands for Notch receptors other than Notch1. Meanwhile, ligand-induced cleavage and nuclear translocation of the Notch protein are considered to be fundamental for Notch signaling, yet direct observation of the behavior of the Notch molecule after ligand binding, including cleavage and nuclear translocation, has been lacking. In this report, we investigated these issues for Notch2. All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells, although characteristics of Jagged2 for binding to Notch2 apparently differed from that of Delta1 and Jagged1. After binding, the three DSL proteins induced cleavage of the membrane-spanning subunit of Notch2 (Notch2(TM)), which occurred within 15 min. In a simultaneous time course, the cleaved fragment of Notch2(TM) was translocated into the nucleus. Interestingly, the cleaved Notch2 fragment was hyperphosphorylated also in a time-dependent manner. Finally, binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. Together, these data indicate that all of these DSL proteins function as ligands for Notch2. Moreover, the findings of rapid cleavage, nuclear translocation, and phosphorylation of Notch2 after ligand binding facilitate the understanding of the Notch signaling.

Animals↗