The road to the production of IgE is long and winding.
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Biomedical subjects
Publications and source records attributed to P Yu.
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Brasofensine (NS-2214) is a dopamine reuptake inhibitor under development by NeuroSearch for the potential treatment of Parkinson's disease (PD) [178224]. The compound entered phase II trials in Denmark in November 1996, and phase I trials in the US in January 1996 [195505], [206604]. Bristol-Myers Squibb (BMS) had been codeveloping the compound until June 1999, when it decided to withdraw from the collaboration due to financial restraints of further regulatory requirements (such as additional toxicology documentation) [318365], [329665]. NeuroSearch was seeking licensing agreements with one or more international pharmaceutical companies to accelerate the development and marketing of brasofensine [187758] and had plans to meet with new potential partners for discussions concerning brasofensine licensing in late 1999 [337221]. A more complete evaluation of the effects of brasofensine was anticipated to be obtained through controlled trials, of at least 3 months duration, comparing it with a placebo and the marketed anti-Parkinson's drug, L-DOPA [317406]. In addition, further animal (monkey) tests were planned in order to document the safety of the drug in long-term treatment. These studies were expected to be discussed with the US FDA in October 1999 and, if satisfactory, the 3-month clinical trials were planned to commence in mid-2000 [337221]. At a meeting with the FDA during 1999, NeuroSearch presented plans for developing brasofensine alone. These were found to be satisfactory on condition that further preclinical studies were performed prior to any more clinical development [371542]. In August 2000, Lehman Brothers predicted worldwide sales of US $45 million in 2002 and US $175 million in 2003 [389229]. In February 1999, Lehman Brothers predicted the drug had a 35% probability of reaching market, with an estimated first launch date in 2002. The analysts predicted peak sales would occur in 2009, with sales of $250 million at that time [319225].
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Measurement of the vibration instability by means of jitter in cases of dysphonia fails to take into account certain features of the vocal signal, such as modulation or bitonatily. These abnormalities appear in jitter measurements as instability, without allowing any differentiation from random instability (to give 'true' instability). The authors suggest the use of the coefficient of Lyapunov, a measurement which is used for nonlinear dynamics. The vocal product of 179 normal and dysphonic subjects has been analysed. The coefficient of Lyapunov and the jitter were measured during the stable period of a sustained 'a' vowel. For the coefficient of Lyapunov, the authors used the algorythm which has been published previously [Giovanni et al, J. Voice 1999;13:341-354]. The measurements were compared with the perceptive analysis of the reading voice by a panel, and divided into four grade (G0 to G3). The coefficient of Lyapunov appeared to be more relevant than the jitter in distinguishing the various perceived grades. Precise recognition of the grade was obtained in 46% using the coefficient of Lyapunov as against only 36% using jitter. The addition of this new index to the existing puriparametric methods of voice analysis seems to be promising.
OBJECTIVE: To investigate expressions of gp-91phox and IL-8 gene and the function of neutrophils in hemodialysis (HD) patients, and to understand the relationship between uremia and immune. METHODS: Gene expression was studied by means of reversal transcription polymerase chain reaction (RT/PCR) from the untreated and treated with lipopolysaccharide (LPS) neutrophils in controls and HD patients. Phagocytosis and bactericidal assays were measured as a decrease in the number of viable intracellular and extracellular bacteria by colony counts. RESULTS: Freshly isolated neutrophils express gp-91phox mRNA in controls while no gp-91phox mRNA was detected in HD patients. When challenged with LPS, gp-91phox mRNA exhibited decreased expression. IL-8 mRNA in HD patients could be spontaneously expressed. Phagocytosis and intracellular killing of neutrophils, when exposed to Staphylococcus aureus, were decreased obviously compared with controls. CONCLUSIONS: The impaired gp-91phox gene expression of neutrophils indicates the impaired NADPH-oxidase system and the untreated neutrophils spontaneously express IL-8 mRNA in the HD patients, which is consistent with suppressed phagocytosis and intracellular killing capacity.
OBJECTIVE: To analyze the causes of death in patients with malignant bile duct obstruction treated by metallic stent endoprosthesis and biliary drainage. METHODS: One hundred and seven patients with malignant bile duct obstruction were so treated. Of the 107 patients, 12 (11.2%) died within 30 days after operation. The bile duct obstruction in the 12 cases was due to primary hepatic cancer(n = 4), metastasis of lymph nodes in hepatic hilus(n = 3) and bile duct cancer(n = 5). RESULTS: Five patients died of biliary infections, 4 patients died of hepatic coma, and 2 patients died of cancerous cachexia and 1 patient died of biliary tract hemorrhage. CONCLUSION: The major causes of postoperative death of patients with biliary obstruction treated by metallic stent to support bile duct are biliary infection and hepatic encephalopathy.
OBJECTIVE: To observe the changes of glutamates (Glu) and gamma-aminobutyric acid (GABA) contents in brain tissue of infectious brain edema, and effects of baicalin on them in rats. METHODS: The high performance liquid chromatography (HPLC) was used to determine the Glu and GABA contents in homogenized brain tissue after baicalin was injected intraperitoneally on infectious brain edema induced by pertussis bacilli in rats. RESULTS: Glu contents of homogenized brain tissue in blank control group (C), normal saline group (NS), pertussis bacilli group (PB) and baicalin group (BC) had no significant difference (P > 0.05). The concentration of GABA was more significantly increased in the BC group (4.06 +/- 0.52) than that in the PB group (2.71 +/- 0.29) (P < 0.05). Water content of brain was reduced in the BC group (79.8 +/- 0.4) as compared with the PB group (82.2 +/- 0.3)(P < 0.01). CONCLUSION: Baicalin has a protective effect against the pertussis bacilli-induced brain edema in rats, and protective effect was correlated to the increased content of GABA in the brain tissue in rats.
OBJECTIVE: To study crude prevalence and distribution of the elderly prostatic hyperplasia. METHODS: Three thousand three hundred and sixty-one elderly aged 60 years and above in the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and Shenyang were investigated, using clustered random sampling methods. RESULTS: The crude prevalence of prostatic hyperplasia was found to be 43.68% with an increase with ageing (P < 0.01). The crude prevalence rates of prostatic hyperplasia among the elderly of 60-, 65-, 70-, 75-, 80-, 85- years old were 34.48%, 40.27%, 46.77%, 51.44%, 57.32% and 60.19% respectively (P < 0.01). Rates in the urban and rural areas were 46.79%and 39.64% respectively. The crude prevalence of urban areas was higher than that of rural areas (P < 0.01) and was found higher in Beijing (63.28%) and Guangzhou (54.28%), (P < 0.01). The crude rates prevalence of managers (54.88%), teachers and business men (55.17%) were in general higher than the prevalence of the workers (41.29%) and peasant (37.26%). Logistic regression analysis showed that the crude prevalence was related to ageing, profession and residential areas (P respective < 0.01). CONCLUSION: The prevalence of prostatic hyperplasia was higher in the elderly and became a common disease of the male elderly in China. Prevention and treatment of prostatic hyperplasia in the elderly should be strengthened.
The residual dynamics of flumioxazin in soil and soybean were determined with HPLC, using a Zorbax SIL column and methylene dichloride-methanol (99.5:0.5, V/V) as mobile phase. A method for pretreatment of samples and analysis was established. Recoveries of flumioxazin in soil, green soybean and soybean were 84.82%-85.63%, 88.79%-94.00% and 93.70%-94.48%, respectively. Flumioxazin degrades relatively slowly and its half-life in soil was 10.0-10.5 days, but in the soil, green soybean and soybean residual flumioxazin was not detected. The results showed that the residual pollution of flumioxazin is negligible, so the application of flumioxazin is safe for the soil and soybean.
In this paper, the enhancement effect of lead was studied in air-acetylene flame. It was found that microemulsion could produce remarkable sensibilization effect. The method has been applied to the determination of lead in copper and waste water.
Trapped as molecular solids, the transition metal fluorides ZnF(2) and MeZnF-the latter isolated for the first time-exist as adducts in [(Cp*TiF(3))(8)(ZnF(2))(3)] (1) and [(Cp*TiF(3))(4)(MeZnF)(2)] (2), respectively. Compounds 1 and 2 were obtained in reactions of [Cp*TiF(3)] (Cp*=C(5)Me(5)) with ZnMe(2) and Me(3)SnF in various molar ratios. The single-crystal structure of 1 is shown here; the unlabeled circles are F atoms.
We describe a 1-year-old boy with mental and physical retardation, a large anterior fontanel, brachycephaly with flat occiput, short and stubby fingers, generalized hypotonia, ocular hypertelorism, low-nasal bridge, long philtrum, high-narrow palate, apparently low-set ears, and a small mandible. Cytogenetic analysis utilizing high resolution chromosome banding technique showed an unbalanced karyotype consisting of 46,XY,add(21)(q22.3) that originated from maternal balanced translocation between chromosomes 7 and 21. Fluorescence in situ hybridization (FISH) using micro-dissected library probe pool from chromosome 7 confirmed the additional material on 21q was derived from chromosome 7. Our results indicated that the patient had an unbalanced translocation, 46,XY, der(21)t(7;21)(p21.2;q22.3)mat, which resulted in duplication for distal 7p. Our patient is similar to reported cases with a 7p15-->pter or larger duplication of 7p, suggesting that the critical segment causing the characteristic phenotype of 7p duplication syndrome, including large anterior fontanel, exists at 7p21.2 or 7p21.2-->pter.
OBJECTIVE: To establish a method for sensitive, specific and rapid detection of the angiotensin converting enzyme(ACE) genotypes and to study the relationship between the ACE gene polymorphism and preeclampsia. METHODS: Sixty patients with preeclampsia and 76 normal pregnant women as controls were investigated. A pair of primers, for the intron 16 of ACE gene was designed. A sensitive and specific method for detecting the ACE polymorphism of the insertion/deletion was established. Determined by polymerase chain reaction (PCR),a 490bp(I) and 190bp(D) PCR product was identified,corresponding to the PCR amplification of the allele with or without the insertion. RESULTS: The subjects were classified, according to the presence or absence of a 287bp insertion in intron 16 of the ACE gene, as II, DD, or heterozygotes for deletion/insertion (DI). The frequency of allele gene (0.75) and the percentage of the ACE DD genotype (65%) in the preeclampsia group were significantly higher as compared with the frequency 10.308 and the percentage (10.5%) in the control group respectively. CONCLUSION: Genotype II of ACE is a marker for reduced risk for preeclampsia and DD is a risk gene.
beta-spectrins are crucial for the maintenance of cell shape, the establishment of cell polarity, and the formation of distinct membrane domains. Our strategy for identifying genes important for hepatocyte polarity has been to utilize subtractive hybridization of early embryonic mouse cDNA liver libraries. As a result, we have cloned three isoforms of a novel beta-spectrin elf (embryonic liver beta-fodrin), and here we report the analysis of elf3, the longest isoform (8172 nt). ELF3 comprises 2154 residues with an overall similarity of 89.0% and 95.3% to mouse beta-spectrin (betaSpIIsigma1) at the nucleotide and amino acid level, respectively. ELF3 is characterized by an actin-binding domain, a long repeat domain, and a short regulatory domain remarkable for the absence of a PH domain. Linkage analysis reveals that elf3 maps to mouse chromosome 11 between D11Bir6 and D11Xrf477, a different chromosomal locus from that of the other four spectrin genes. Northern blot analysis utilizing an elf3 3'-UTR probe demonstrates an abundant 9.0-kb transcript in brain, liver, and heart tissues. Western blot with a polyclonal antibody against ELF identifies a 200 kD protein in mouse liver, brain, kidney, and heart tissues. Immunohistochemical studies demonstrate ELF labeling of the basolateral or sinusoidal membranes surface as well as a granular cytoplasmic pattern in hepatocytes. Antisense studies utilizing cultured liver explants show a vital role of elf3 in hepatocyte differentiation and intrahepatic bile duct formation. The differential expression, tissue localization, and functional studies demonstrate the importance of elf3 in modulating interactions between various components of the cytoskeleton proteins controlling liver and bile duct development.
OBJECTIVES: To determine the relationship between stroke and lower esophageal dysfunction with vomiting and to identify an optimal nutrition protocol based on our findings. PATIENTS AND METHODS: The lower and upper esophageal sphincter functions were assessed in 35 patients who had an acute stroke to determine whether gastric or jejunal enteral feeding was the optimal route. Stroke was due to unilateral ischemia in 20 patients, unilateral intracerebral hemorrhage in 8 patients, and global ischemia in 7 patients. Our study consisted of 18 men and 17 women with an average age of 64 years. RESULTS: Using standard esophageal manometric definitions, the lower esophageal sphincter function was below normal in 24 patients: 3 had global anoxia, 5 had unilateral hemorrhage, and 16 had unilateral ischemia. The upper esophageal sphincter function was low in 30 patients: 6 had global anoxia, 7 had unilateral hemorrhage, and 17 had unilateral ischemia. Based on lower esophageal sphincter pressure, 7 patients underwent tube gastrostomy and 13 patients underwent tube jejunostomy placement. All tolerated enteral alimentation well. Prior to lower esophageal sphincter assessment, 4 patients had percutaneous endoscopy gastrostomy feedings that led to aspiration pneumonitis and consultation for tracheostomy; 2 terminally ill patients were referred to the ethics service, and 2 were converted to feeding via jejunostomy tube at the time of tracheostomy and did well. CONCLUSIONS: Vomiting with aspiration due to lower esophageal sphincter dysfunction is common after acute strokes. Esophageal manometry serves as a guide to find the optimal feeding route.
CD40-deficient mice, when inoculated with the LP-BM5def murine retorvirus, become infected and show virus expression similar to wild-type mice. However, unlike the wild-type mice, CD40-deficient mice do not develop symptoms of immunodeficiency, lymphoproliferative disease and the typical histological changes in the lymphoid tissue. These results show that the CD40-CD40 ligand (CD40L) interaction in vivo is essential for anergy induction and the subsequent development of immunodeficiency and pathologic expansion of lymphocytes. Infected CD40-deficient mice and their littermates express a similar pattern of cytokine mRNA, which is not biased towards a Th2 phenotype. Nevertheless, hypergammaglobulinemia is induced in infected wild-type and CD40-deficient mice. Surprisingly, murine AIDS infection even induces IgE production in CD40-deficient mice in vivo. Our data demonstrate that antibody class switch to IgE and IgG1 can be induced by a retroviral infection in vivo even in the absence of CD40-CD40L interaction and an apparent switch to a Th2 cytokine production.
The aim of our study was to isolate novel gene(s) involved in cell differentiation and embryonic liver development. Mouse cded/lior was identified from subtraction hybridization of embryonic liver cDNA libraries as well as an adult mouse liver genomic DNA library. The full open reading frame of cded/lior encodes a 131-amino acid protein with 71.88% overall similarity to the PH domain of rat PLC-gamma1. A gapped search with the C-terminal region of CDED/LIOR revealed a 36-41% similarity to several proteins related to signal transduction and cell replication, such as ORC1 and KSR. Northern blot analysis of adult mouse tissues shows a strong 2.6-kb transcript restricted to heart and skeletal muscle. RT-PCR utilizing cded/lior-specific primers demonstrates cded/lior mRNAs in heart, brain, and liver tissue throughout mid-embryonic mouse gestation. cded/lior maps to the distal end of mouse Chromosome (Chr) 2. Analysis of the genomic structure for cded/lior demonstrated a single exon gene that is not an alternatively spliced isoform of PLC-gamma1. Analysis of the cded/lior promoter region revealed a high GC-content, high ratio of CpG/GpC, multiple GC-boxes, the lack of a TATA box, CTF/NFI element, and two MyoD-MCK binding sites. These characteristics are also found in several genes important in the regulation of cell growth or DNA synthesis, such as transforming growth factor-beta1, c-Ha-ras, nerve growth factor, epidermal growth factor receptor, and DNA polymerase beta. These results suggest that cded/lior is a mesoderm/muscle-specific transcript that may be involved in the mesodermal inductive and regulatory interactions required for liver formation and embryonic development.
Decreased levels of the endogenous neuroprotectant kynurenic acid (KYNA) have been observed in the brain of Huntington's Disease (HD) patients and may be related to neuronal loss in this disorder. This reduction may be caused by a dysfunction of kynurenine aminotransferase II (KAT II), the major enzyme responsible for the synthesis of KYNA in the brain. Towards understanding the role of KAT II in HD, we isolated and characterized the cDNA sequence and determined the genomic organization of mouse KAT II (mKat-2). The full length mKat-2 cDNA is 1812 bp, encoding 425 amino acids, and shares 89.9% amino acid similarity with the rat Kat-2 sequence. The gene for mKat-2 is composed of 13 exons divided by 12 intronic sequences. Northern blot analysis demonstrated that mKat-2 mRNA is mainly expressed in kidney and liver. RT-PCR showed mKat-2 expression in the brain starting from at least d11 of embryonic development. An alternative isoform mKat-2beta, derived from the usage of novel exons, shows a different expression pattern from mKat-2. Western blot analysis of various mouse tissues shows a 40-kDa protein in brain, heart, kidney, and liver. In the kidney and liver an additional 45-kDa isoform was detected. Use of the BSS chromosomal mapping panel from The Jackson Laboratory indicates that the mKat-2 gene co-segregates with polymorphic markers D8Mit129 and D8Mit128 on mouse Chr 8. Knowledge of the genomic organization, the isoform tissue-specific expression patterns, the chromosomal localization of mKat-2, and the reagents generated here, will provide the tools for further studies and allow generation and characterization of mice that are nullizygous for mKat-2.