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Biomedical subjects

S Ida

Publications and source records attributed to S Ida.

At least 19 recordsLinked to original sources

A 13C-urea breath test in children with helicobacter pylori infection: assessment of eradication therapy and follow-up after treatment.

PURPOSE: Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. METHODS: Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. RESULTS: Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. CONCLUSIONS: The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

Adolescent↗

Prospective study of mother-to-infant transmission of hepatitis C virus.

BACKGROUND: Mother-to-infant transmission of hepatitis C virus (HCV) could become the main route of HCV infection in the future because there are no methods available to prevent vertical infection. The aim of this study was to determine the incidence of mother-to-infant transmission in infants born to mothers who tested positive for anti-HCV antibodies and to elucidate associated risk factors for transmission. METHODS: Screening was conducted for 16,800 pregnant women with an anti-HCV antibodies test, and 154 mothers were positive. From the positive group 141 mothers were enrolled in the study and their 147 infants were followed from birth for serum alanine aminotransferase activity, anti-HCV antibodies and HCV RNA. HIV infection was tested in 73 of 141 mothers, all of whom were negative. RESULTS: Thirty-three infants were dropped from the study because they were followed for <6 months or were not tested adequately. Of the 114 infants finally evaluated 9 (7.8%) had detectable HCV RNA. The transmission rate was not influenced by the mode of delivery [vaginal delivery, 8 of 90 vs. cesarean section, 1 of 24 (P = 0.396)] or by the type of feeding [9 of 98 for breast-fed infants vs. 0 of 16 for formula-fed infants (P = 0.243)]. All infected infants were born to mothers who had HCV viremia at the delivery (P = 0.040) and to those with a high viral load (P = 0.019). CONCLUSIONS: Our prospective study showed that the transmission rate of mother-to-infant HCV infection was 7.8% in anti-HCV antibody-positive mothers. Risk was related to the presence of maternal HCV viremia at delivery and a high viral load in the mothers.

Alanine Transaminase↗

Nitrite reductase gene enrichment improves assimilation of NO(2) in Arabidopsis.

Transgenic plants of Arabidopsis bearing the spinach (Spinacia oleracea) nitrite reductase (NiR, EC 1.7.7.1) gene that catalyzes the six-electron reduction of nitrite to ammonium in the second step of the nitrate assimilation pathway were produced by use of the cauliflower mosaic virus 35S promoter and nopaline synthase terminator. Integration of the gene was confirmed by a genomic polymerase chain reaction (PCR) and Southern-blot analysis; its expression by a reverse transcriptase-PCR and two-dimensional polyacrylamide gel electrophoresis western-blot analysis; total (spinach + Arabidopsis) NiR mRNA content by a competitive reverse transcriptase-PCR; localization of NiR activity (NiRA) in the chloroplast by fractionation analysis; and NO(2) assimilation by analysis of the reduced nitrogen derived from NO(2) (NO(2)-RN). Twelve independent transgenic plant lines were characterized in depth. Three positive correlations were found for NiR gene expression; between the total NiR mRNA and total NiR protein contents (r = 0.74), between the total NiR protein and NiRA (r = 0.71), and between NiRA and NO(2)-RN (r = 0.65). Of these twelve lines, four had significantly higher NiRA than the wild-type control (P < 0.01), and three had significantly higher NO(2)-RN (P < 0.01). Each of the latter three had one to two copies of spinach NiR cDNA per haploid genome. The NiR flux control coefficient for NO(2) assimilation was estimated to be about 0.4. A similar value was obtained for an NiR antisense tobacco (Nicotiana tabacum cv Xanthi XHFD8). The flux control coefficients of nitrate reductase and glutamine synthetase were much smaller than this value. Together, these findings indicate that NiR is a controlling enzyme in NO(2) assimilation by plants.

Aminomethyltransferase↗

Rapid and simple phenotypic assay for drug susceptibility of human immunodeficiency virus type 1 using CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5).

We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 10(4) copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.

Amino Acid Sequence↗

Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells: effects on platelet-activating factor receptor expression.

To examine the effects of acid exposure on the adherence of Streptococcus pneumoniae to cultured human tracheal epithelial cells, cells were exposed to acid at various pH levels, and various concentrations of S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to cultured human tracheal epithelial cells increased after acid exposure. Y-24180, a specific inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself decreased the number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the activation of transcription factor nuclear factor (NF)-kappa B and the expression of protein and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the content of interleukin (IL)-1 alpha and IL-1 beta in the culture supernatants, but monoclonal antibodies to IL-1 alpha and IL-1 beta failed to inhibit the increased number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. These findings suggest that acid exposure stimulates the adherence of S. pneumoniae to the airway epithelial cells via increases in PAF receptors. Increases in PAF receptor expression may be, in part, mediated via activation of transcription factors and subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of S. pneumoniae may be one of the reasons why pneumonia develops after gastric juice aspiration.

Aged↗

[Mesial temporal lobe epilepsy in a patient with Wilson's disease receiving FK506 (tacrolimus) after liver transplantation].

Mesial temporal lobe epilepsy (MTLE) developed in a boy receiving FK506 (tacrolimus) after liver transplantation. He had no history of convulsions. At the age of 7, he underwent liver transplantation 13 days after he developed the abdominal form (fulminant hepatitis) of Wilson's disease. On postoperative day 18, he had a generalized tonic seizure (duration 20 min.) with loss of consciousness. FK506 was discontinued under the suspicion of FK506-induced encephalopathy. His symptoms resolved within a few days. FK506 was readministered at 3 months after transplantation. Ten months later, he developed complex partial seizures characterized by right tonic posturing with oral automatism. EEG revealed sporadic spikes in the anterior temporal region. MRI and SPECT showed bilateral (left side dominant) hippocampal lesion, which suggested the diagnosis of MTLE. Since seizures became refractory to medical treatment with progressive worsening of memory functions, FK506 was discontinued again at 36 months after readministration. Six months later, his memory improved remarkably, but there were no changes in seizure frequency and in MRI and SPECT findings. Our findings indicate that FK506 might damage the hippocampus, thereby causing MTLE. Additional case reports, however, will be required to elucidate this new FK506-related neurological complication.

Child↗

[Evaluation of the new pump for home parenteral nutrition Terumo Cafty].

This study was undertaken to evaluate the usefulness of 'Cafty' which is a new infusion pump system for administering home parenteral nutrition (HPN), recently launched by Terumo Corporation. We used 'Cafty' in two patients and found it has more advantages than the existing pump with regard to the following points: 1. Cafty is provided with a display and alarms that indicate pump troubles such as emptiness, occlusion or mis-operation. 2. It is easier to carry because of its smaller size (width 80 mm x length 132 mm x thickness 33 mm) and its lighter weight (320 g). 3. While Cafty operation using a cassette-type tubing and plain control panel to simpler the flow rate accuracy is not reduced. In conclusion, Cafty is better than the existing HPN pump from the viewpoint of safety, portability and easiness.

Adolescent↗

Extrasolar planets.

The first known extrasolar planet in orbit around a Sun-like star was discovered in 1995. This object, as well as over two dozen subsequently detected extrasolar planets, were all identified by observing periodic variations of the Doppler shift of light emitted by the stars to which they are bound. All of these extrasolar planets are more massive than Saturn is, and most are more massive than Jupiter. All orbit closer to their stars than do the giant planets in our Solar System, and most of those that do not orbit closer to their star than Mercury is to the Sun travel on highly elliptical paths. Prevailing theories of star and planet formation, which are based on observations of the Solar System and of young stars and their environments, predict that planets should form in orbit about most single stars. However, these models require some modifications to explain the properties of the observed extrasolar planetary systems.

Journal Article↗

Two cases of persistent hyperinsulinemic hypoglycemia that showed spontaneous regression and maturation of the Langerhans islets.

Near-total pancreatectomy has been recommended as the treatment for persistent hyperinsulinemic hypoglycemia (PHH) in infants. However, recently there has been a report described that one third of 95% pancreatectomy failed to prevent hypoglycemia and more than two thirds had diabetes ultimately. The authors experienced 2 cases of PHH, which raise a query about the extensive pancreatectomy. Case 1: A female patient who manifested PHH shortly after birth underwent less extensive pancreatectomy twice at age 2 months and 8 years. After each operation, her clinical symptoms regressed, and she became free from the disease eventually. Histologic findings showed nesidioblastosis in which the islets clearly matured. Case 2: A male infant with PHH had an absolute indication for pancreatectomy. However, after a meticulous control of the blood glucose level with parenteral nutrition followed by continuous enteral nutrition feeding combined with medication, he became free from the disease. The current cases show there exist cases of PHH in which the islets mature and symptoms regress spontaneously. Therefore, we conclude near-total pancreatectomy is not always the treatment of choice. As an alternate strategy, long-term controlled feeding and medication combined with or without less extensive pancreatectomy should be considered with the expectation of spontaneous regression.

Adenoma, Islet Cell↗

[A two-year follow-up of zidovudine plus lamivudine combined with indinavir in antivival naive HIV-infected patients].

Efficacy of a 3-drug combination (Zidovudine (AZT) + Lamivudine (3TC) + Indinavir (IDV)) has been evaluated in 17 anti-viral naive patients with HIV infection for 24 months. Our genotypic resistance assay was able to analyze more than 80% of the patients whose viral load (VL) was over 3,000 copies/ml. This therapy was continued in 11 patients (65%) for 24 months. Among them, VL was undetectable (VL < 400 copies/ml) in patients at 24 month (47% by intent-to-treat, 72% by on treatment). Of the 11 patients, a 3TC resistance-related mutantion was detected in only one case. The therapy was discontinued in 6 cases. Main reasons of the discontinuation were side effects. However, if the therapy was switched to other combinations when VL was undetectable, VL remained undetectable in 5 cases at 24 month.

Anti-HIV Agents↗

Effects of lithium on the pharmacokinetics of valproate in rats.

Combined treatment with lithium and valproate has been used for bipolar disorder. However, the studied interaction between these two drugs has not been fully investigated. We therefore examined the effects of lithium on the pharmacokinetics (plasma disappearance, metabolism and urinary excretion) of valproate in rats. Lithium (2 mEq kg(-1)) was administered intraperitoneally twice a day for ten days. Plasma disappearance curves of valproate (50 mg kg(-1), i.v.), valproate-metabolizing activities of UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) in liver microsomes and urinary excretion of free valproate and valproate-glucuronide were examined. The metabolizing activity of UGT and CYP were determined by enzyme assays and a fluorescence polarization immunoassay system. Urinary valproate-glucuronide was obtained using this system by subtracting the free level from total level, which was determined after deconjugating the sample with heat and NaOH. The half-life of plasma disappearance of valproate was 25% reduced by lithium pretreatment (0.428 +/- 0.031 h with repeated lithium pretreatment vs 0.578 +/- 0.062 h for controls). The valproate-metabolizing activity of UGT and CYP were not altered by lithium although lithium increased the urinary excretion of valproate-glucuronide. In conclusion, lithium pretreatment causes a decrease in plasma valproate levels and an increase in urinary excretion of valproate-glucuronide in rats.

Animals↗

Identification of highly selective inhibitors of collagenase-1 from combinatorial libraries of diketopiperazines.

Thiol-containing diketopiperazines have been recently identified as novel heterocyclic inhibitors of matrix metalloproteinase (MMPs). The compounds described had similar activities against the MMPs collagenase-1 and gelatinase-B. An inhibitor that showed greater than 10-fold selectivity for collagenase-1 over gelatinase-B was desired. Previously published work with peptidyl hydroxamates and thiols indicated that while preparing gelatinase selective inhibitors was straightforward, there was not an obvious route to selective inhibitors of collagenase-1. Combinatorial libraries were prepared and evaluated for their ability to inhibit collagenase-1 and gelatinase-B substrate hydrolysis. A method for estimating the IC50 values of compounds generated by high-throughput parallel synthesis aided in the identification of compounds with the desired properties. We have found that thiol diketopiperazines derived from nitrophenylalanine are both potent and selective inhibitors of collagenase-1. In addition, we have demonstrated that combinatorial chemistry can be utilized to identify molecules with a desired selectivity profile without access to the traditional tools of rational drug design.

Drug Design↗

Active HIV-1 redistribution and replication in the brain with HIV encephalitis.

The central nervous system (CNS) is of particular importance in human immunodeficiency virus type 1 (HIV-1) infection. First, the CNS may be difficult to access for anti-retroviral treatment and may become a sanctuary for residual viruses. Second, HIV-1 infection may lead to AIDS dementia complex (ADC) culminating in HIV-1 encephalitis. In order to examine the pattern of drug resistance and the role of encephalitis in enhancing viral redistribution to the CNS, we compared pol gene quasispecies of the spleen and brain in two patients with and two patients without HIV-1 encephalitis, who had been treated with zidovudine (AZT). Although a variable degree of AZT resistance was noted in both the spleen and brain of all patients, phylogenetic analysis indicated that quasispecies developed rather independently in the systemic circulation (spleen) and CNS (brain) of patients without HIV-1 encephalitis, while similar pol gene sequences were obtained from the two compartments of patients with HIV-1 encephalitis. env gene V3 region of patients with HIV-1 encephalitis showed distinct quasispecies in the spleen and brain. Our results suggest that HIV-1 redistribution to CNS is more active in cases with encephalitis and that HIV-1 distributed late to CNS grow actively under certain selective pressure exerted on the V3 region of the env gene.

AIDS Dementia Complex↗

Genetic alterations in the JAG1 gene in Japanese patients with Alagille syndrome.

Alagille syndrome (AGS) is a congenital anomaly syndrome that affects liver, heart, pulmonary artery, eyes, face, and skeleton. Recently, mutations of the JAG1 gene, which encodes a ligand for the Notch receptor, have been identified in AGS patients. We investigated the JAG1 gene for genetic alterations in eight Japanese AGS patients, using fluorescence in situ hybridization (FISH), single strand conformation polymorphism (SSCP) analysis, and direct sequencing. Subtle genetic alterations were identified in six of the eight patients, including three frameshift mutations, two splice donor mutations, and one nonsense mutation. All alleles with identified mutations can be expected to produce non-functional truncated proteins without a transmembrane domain. There was no apparent correlation between the genotypes of the patients and their affected organs, although the phenotypes of the patients with mutations at the splice donor site were found to be less severe.

Alagille Syndrome↗

Reduction in interleukin-2-producing cells but not Th1 to Th2 shift in moderate and advanced stages of human immunodeficiency virus type-1-infection: direct analysis of intracellular cytokine concentrations in CD4+ CD8- T cells.

Previous studies have suggested that CD4+ T lymphocytes shift from the Th1 type to the Th2 type during disease progression in patients with the human immunodeficiency virus type-1 (HIV-1). In the present study, we used a modified method that allowed a direct measurement of intracellular cytokines in CD4+ CD8- T cells. A total of 48 HIV-1-infected (HIV+) and 16 HIV-1-uninfected (HIV-) individuals were studied. The percentages of CD4+ CD8- T cells producing interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), or interleukin-5 (IL-5) in HIV+ and HIV- subjects were 23.6% versus 34.9% (P < 0.01), 13.7% versus 13.2%, 1.3% versus 1.0%, and 1. 2% versus 0.9%, respectively. The population of IL-2-producing cells decreased proportionately with reductions in CD4 counts (< 200/mm3, 200-500/mm3, and > 500/mm3 to 18.0%, 23.5%, and 30.5%, P < 0.05, respectively). There was an inverse correlation between the percentage of IL-2-producing cells and plasma viral load (r = - 0. 446, P < 0.05). However, the percentages of CD4+ CD8- T cells producing other cytokines were not different between HIV+ and HIV-. Our cross-sectional study demonstrated a decrease in IL-2-producing cells but not the Th1 to the Th2 shift in the CD4+ CD8- T cell population in the moderate and advanced stages of HIV-1-infection.

Adult↗