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Biomedical subjects

L Yu

Publications and source records attributed to L Yu.

At least 289 records · Page 16Linked to original sources

Langerhans cell histiocytosis: unusual skeletal manifestations observed in thirty-four cases.

OBJECTIVE: Unusual manifestations are occasionally encountered in Langerhans cell histiocytosis and may be a source of confusion. The objective of this study was to determine the frequency of occurrence of the unusual manifestations in our case material. DESIGN AND PATIENTS: Thirty-four children, average age 4.4 years (range 3 months to 16 years) with 262 skeletal lesions of biopsy-proven Langerhans cell histiocytosis (LCH) were retrospectively reviewed to determine the frequency of occurrence of unusual manifestations defined either as an atypical location of a skeletal lesion or an atypical radiographic appearance of the lesion. RESULTS: Twenty-four unusual lesions were found in this retrospective review. Among these were epiphyseal lesions, transphyseal lesions, extracranial 'button' sequestra, posterior vertebral arch lesions, dural extension of vertebral lesions, and fluid-fluid levels. The finding of fluid-fluid levels has not previously been described in the radiologic literature. Involvement of unusual sites included clavicles and small bones of the hands and feet. CONCLUSIONS: Radiographic, computed tomographic, and magnetic resonance imaging of LCH yield a variety of unusual manifestations. Recognition of these varied appearances of LCH may prevent confusion of such appearances with other pathologic processes. When the unusual manifestation occurs as the initial finding of the disease, LCH should be included in the differential diagnosis.

Adolescent↗

Epitope mapping of monoclonal antibodies by mass spectrometry: identification of protein antigens in complex biological systems.

We describe the application of immunoaffinity extraction and mass spectrometry to the analysis of Ty1 Gag protein in lysates of Saccharomyces cerevisiae. A magnetic bead-conjugated monoclonal antibody was used to achieve selective extraction, the specificity of which was established by matrix-assisted laser desorption/ionization mass spectrometric (MS) analysis of an extract of the lysate of cells overexpressing the Ty1 Gag protein. MS analysis of similar extracts of lysates following tryptic hydrolysis confirmed selective extraction of the epitope-containing peptide fragment. Sufficient sensitivity was achieved to allow the application of this approach to the analysis of lysates of wild-type cells. Furthermore, the sequence of the epitope-containing peptide was confirmed by electrospray-tandem MS. To our knowledge, this constitutes the first report of the application of immunoaffinity extraction and tandem MS analysis to the characterization of an antigen recovered from a complex cellular system.

Antibodies, Monoclonal↗

Determination of the glass properties of D-mannitol using sorbitol as an impurity.

Due to its strong tendency to crystallize, the glass properties of mannitol cannot be measured directly. However, because mannitol can exist in a fully or partially amorphous state in drug formulations, it is important to determine the glass properties of mannitol. We obtained the glass properties of mannitol by introducing a small amount of sorbitol, an isomer of mannitol, to delay the onset of crystallization. Extrapolation to zero sorbitol concentration yielded the following properties for the mannitol glass: Tg onset = 10.7(o)C, Tg midpoint= 12.6( o)C, Tg end = 18.4 degreesC and DeltaCp = 1.27 J/g/K. In addition, we estimated the following parameters of the mannitol glass from the width of glass transition using the results of Moynihan (J. Am. Ceram. Soc. 1993, 76, 1081) and Angell (J. Phys. Chem. 1994, 98, 13780): DeltaH (at Tg onset) = 103 kcal/mol, D = 11, and T0 = 222 K. The value of T0 is consistent with the Kauzmann temperature TK (236 K) obtained calorimetrically. The properties of the mannitol glass may be useful for predicting the behavior of amorphous mixtures containing mannitol.

Calorimetry, Differential Scanning↗

Isolation of 24 novel cDNA fragments from microdissected human chromosome band.

The strategy of isolating the band-specific expression fragments from a probe pool generated by human chromosome microdissection was reported. A chromosome 14q24.3 band-specific single copy DNA pool was constructed based on this probe pool. Using total DNA of the pool as probe to hybridize the human marrow cDNA library, 68 primary positive clones were selected from 5 x 10(5) cDNA clones. Among these primary clones, 32 secondary clones were obtained after second-round screening and designed as cFD14-1-32. Finally, 24 band-specific expression fragments were identified from these 32 positive clones by DNA hybridization. Those band-specific clones can hybridize to both 14q24.3 DNA and human genomic DNA but can't hybridize to 17q11-12 DNA. Partial sequences of 13 fragments of them were sequenced and identified as novel cDNA sequences, and these sequences were proved to have some homology with known genes in NCBI database. Analysis of expression spectrum of cFD14-1 suggested that the cDNA fragments thus obtained should be used to isolate the genes can not been cloned in 14q24.3 region.

Blotting, Northern↗

Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans.

A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody.The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals.

Administration, Topical↗

Genetic linkage analysis using lognormal variance components.

Typically genetic studies of continuous traits such as cholesterol levels or blood pressure assume that interindividual variability follows a normal distribution. Here we develop methods to analyze positively skewed data by assuming a lognormal distribution. We develop a variance components approach for identifying such effects from a major gene, residual polygenic factors and nongenetic factors. We compare by a simulation study results from fitting this lognormal model with either applying the log transformation or not transforming the data. We found that the lognormal model provided more precise estimates and more powerful tests than a simple log transformation when analyzing lognormally distributed data. Power varied with sibship size. For the same total number of nonindependent sibpairs, larger sibships were less powerful. However, larger sibships are more economical because they require a smaller sample size to obtain a specified power. To illustrate the application of this lognormal model to real data, we studied evidence for linkage between triglycerides and the lipoprotein lipase gene.

Genetic Linkage↗

Direct effect of branched-chain amino acids on the growth and metabolism of cultured human hepatocellular carcinoma cells.

Little is known about the influence of amino acid imbalance by supplementation of branched-chain amino acids (BCAAs) on human hepatocellular carcinoma (HCC). We investigated the effect of various BCAA concentrations in culture medium on the growth and metabolism of two human HCC cell lines: Hep G2 and KYN-1. DNA and protein syntheses were studied by radiolabeled thymidine and leucine uptake, Amino acid concentrations in cell and medium were measured with an amino acid analyzer. Expression and excretion of transforming growth factor (TGF)-alpha and TGF-beta1 were studied by immunostaining and enzyme linked immunosorbent assay methods. The cell growth was suppressed in media with higher and lower BCAA concentrations than Dulbecco's modified Eagle's medium, and this was grossly correlated with the incorporation of [3H]thymidine into DNA and incorporation of [3H]leucine into intracellular protein. Pretreatment with 10,000 nmol/ml of BCAA did not suppress the cell growth in subsequent culture in the standard Dulbecco's modified Eagle's medium, indicating that the effect of BCAAs was not cytocidal but cytostatic and reversible. BCAA and aromatic amino acid concentrations in cells increased in parallel as the BCAA level in medium was increased, despite the fixed aromatic amino acid level. Intracellular expression and extracellular excretion of TGF-alpha were higher at BCAA concentrations of 100 and 1,000 nmol/ml than at 10 or 1,000 nmol/ml. The present finding that the in vitro growth of HCC can be suppressed by enriched BCAA levels in medium may indicate that amino acid-imbalanced therapy with enriched BCAAs is useful in the treatment of HCC.

Amino Acids↗

A novel electron transfer mechanism suggested by crystallographic studies of mitochondrial cytochrome bc1 complex.

The crystal structure of bovine mitochondrial cytochrome bc1 complex, an integral membrane protein complex of 11 different subunits with a total molecular mass of 242 kDa, demonstrated a tightly associated dimer consisting of three major regions: a matrix region primarily made of subunits core1, core2, 6, and 9; a transmembrane-helix region of 26 helices in the dimer contributed by cytochrome b, cytochrome c1, the Rieske iron-sulfur protein (ISP), subunits 7, 10, and 11; and an intermembrane-space region composed of extramembrane domains of ISP, cytochrome c1, and subunit 8. The structure also revealed the positions of and distances between irons of prosthetic groups, and two symmetry related cavities in the transmembrane-helix region upon dimerization of the bc1 complex. Extensive crystallographic studies on crystals of bc1 complexed with inhibitors of electron transfer identified binding pockets for both Qo and Qi site inhibitors. Discrete binding sites for subtypes of Qo site inhibitors have been mapped onto the Qo binding pocket, and bindings of different subtypes of Qo site inhibitors are capable of inducing dramatic conformational changes in the extramembrane domain of ISP. A novel electron transfer mechanism for the bc1 complex consistent with crystallographic observations is discussed.

Animals↗

Definition of multiple ICA512/phogrin autoantibody epitopes and detection of intramolecular epitope spreading in relatives of patients with type 1 diabetes.

The related tyrosine phosphatase-like proteins, islet cell antigen 512 (ICA512) and phosphatase homologue in granules of insulinoma (phogrin), are major targets of autoantibodies in patients with type 1 diabetes. In the current study, we have examined the overlapping specificities and antigenic epitopes of autoantibodies to ICA512 and phogrin and determined whether intramolecular epitope spreading occurs during the development of diabetic autoimmunity. ICA512 autoantibodies and phogrin autoantibodies were detected in 65-70% (n = 110) of patients with new-onset type 1 diabetes and 60-65% (n = 42) of prediabetic relatives of patients with type 1 diabetes. Of the sera, 10% reacted with ICA512 but not phogrin, whereas only 1% of sera reacted with phogrin but not ICA512. The binding of phogrin autoantibodies in 88 dual (ICA512 and phogrin) autoantibody-positive sera could be completely blocked by excess recombinant ICA512, whereas the blocking of ICA512 autoantibodies with recombinant phogrin was only partial (mean inhibition of 58.9 +/- 3.7%, mean +/- SE). Binding and competition analysis using multiple chimeric ICA512/phogrin constructs demonstrated that a major unique epitope for ICA512 autoantibodies is localized to amino acids 762-887. A conformational epitope associated with the carboxy-terminal 31 amino acids of ICA512 was recognized by one-third of sera, and a minor epitope is located on amino acids 601-762 of ICA512. The major epitopes for phogrin-selective autoantibodies were localized to amino acids 640-922 of phogrin. Sequential serum samples were analyzed in 22 relatives who expressed ICA512/phogrin autoantibodies. Intramolecular epitope spreading was found for 5 of 13 relatives who have progressed to type 1 diabetes. Among nine relatives who have remained nondiabetic, three demonstrated a decrease in the number of epitopes recognized. These studies highlight the complexity of autoantibody recognition of ICA512/phogrin and are consistent with the hypothesis that ICA512/phogrin may be recognized as a consequence of beta-cell destruction.

Adolescent↗

Probucol inhibits oxidized-low density lipoprotein-induced adhesion of monocytes to endothelial cells by reducing P-selectin synthesis in vitro.

Probucol (PBC) is an unique antiatherogenic drug producing its effect by antioxidant action rather than hypolipidaemic effect. However, the exact mechanism of its antiatherogenic effect is unclear. Therefore we investigated the PBC effects on the adhesion of monocytes to endothelial cells, an early event in atherogenesis. Monocyte adhesion to cultured pig aortic endothelial cells (EC) was induced by oxidized low density lipoprotein (Ox-LDL). To elucidate the mechanisms of the inhibition on adhesion, PBC effects on the Ox-LDL-induced expression of P-selectin, on the synthesis of von Willebrand factor (vWF) and prostacyclin (PGI2) were examined. The results showed that Ox-LDL enhanced the adhesion of monocytes to EC in a concentration-dependent and time-related manner. PBC 25, 50 and 75 micromol/L inhibited the Ox-LDL-induced adhesion index from 37.3% to 19.7, 16.6 and 14.6% respectively (p all < 0.05), and inhibited the Ox-LDL-induced expression of P-selectin from 293.0 ng/ml to 180.0, 132.9 and 132.6 ng/ml respectively. Furthermore, PBC significantly attenuated the Ox-LDL-impaired synthesis of PGI2 and vWF. These results indicate that PBC may provide a new approach in the prevention of atherosclerosis (AS) by intervention of monocyte adhesion to EC. In conclusion, PBC inhibits the Ox-LDL-induced adhesion of monocytes to EC. This effect is associated with the inhibition of the Ox-LDL-induced expression of P-selectin and the protection on the synthesis of PGI2.

Animals↗

Targeted diagnosis and treatment of superficial bladder cancer with monoclonal antibody BDI-1.

OBJECTIVE: To explore the application of monoclonal antibody (McAb) to targeted treatment of bladder carcinoma through a series of in vitro and in vivo studies carried out in animal model and patients with bladder carcinoma. METHODS: Monoclonal antibody BDI-1 against bladder carcinoma was prepared by the lymphocyte hybridoma technique. McAb was conjugated with 99mTc by direct reduction method. Momodin (MD) was covalently linked to McAb by SPDP method. Radioimmunoimaging of nude mice xenografts and patients with bladder carcinoma were performed with BDI-1-99mTc conjugates. An immunotoxin (BDI-1-MD) was inducted via a catheter into the bladder. Targeted treatment with BDI-1-MD was carried out in 18 patients. RESULTS: This study showed the specificity of McAb, and clear imaging of nude mice bearing xenografts. Distribution analysis of 99mTc-BDI-1 in nude mice showed the highest value of T/NT in bladder tumor. Targeted diagnosis and treatment for patients by intravesical administration are very safe and effective. CONCLUSION: The bladder cancer seems an ideal model for diagnostic and therapeutic approaches using regional administration of McAb conjugates via a catheter direct into the bladder.

Animals↗

Detection of Fas/APO-1 in six human urogenital malignant cell lines with flow cytometry.

OBJECTIVE: To investigate the expression of Fas/APO-1 in urogenital tumor cell lines. METHODS: With direct immunofluorescence, the expression of Fas/APO-1 in six urogenital malignant cell lines and one primary in vitro cultured normal renal fibroblast was detected by flow cytometry. RESULTS: Expression of Fas/APO-1 was detected in all six urogenital tumor cell lines, but with limited positive cell percentage and relatively lower fluorescence intensity, compared with expression of Fas/APO-1 in normal control of primary in vitro cultured renal fibroblast. CONCLUSIONS: Lower expression of Fas/APO-1 in urogenital malignant cell lines than that in normal cells might be the reason for occurrence and progression of urogenital malignant tumors.

Apoptosis↗

Diagnosis and classification of hepatic echinococcosis by ultrasonography.

OBJECTIVE: To make an early and correct diagnosis of hepatic echinococcosis. METHODS: A total of 1092 patients with hepatic echinococcosis underwent operation in our hospital between 1984 and 1995. Of these patients, 427 (39.1%) were cases with complications, including secondary infection, rupture, obstructive jaundice, anaphylactic shock, disseminated implantation with resultant multiple echinococcosis and portal hypertension. The ultrasonic examination has been generally used in clinical practice for comprehensive evaluation which can dectedct the preoperative diagnostic accuracy rate. RESULTS: B-mode ultrasonography can be used not only to detect the location, dimension and pathological characteristics of hydatid cyst but also to show the pathological changes of various complications caused by echinococcosis. Seven patterns specific ultrasonic scanning images were revealed. In this series the diagnostic accuracy rate reached 98.8%. CONCLUSIONS: Ultrasonic examination is harmless to human body, and has been widely used in combination with immunological tests in clinical and epidemiological studies to detect the asymptomatic parasite carriers in early stage and to improve the preoperative diagnostic accuracy rate.

Echinococcosis, Hepatic↗

[Treatment of ischemia in lower extremities by primary arterization in situ of Vana saphena magna].

In order to summarize the experience in the treatment of ischemic necrosis of lower extremities resulted from thrombotic occluded angittis, 15 cases were reported, which were treated by primary arterization in situ of V. Saphena magna. With a period of follow-up, 4-26 months on the average, it was found that symptoms in 14 cases were much allayed obviously, except 1 case with little relief. It suggested that primary arterization in situ of V. saphena magna could improve the circulation of the ischemic extremity rapidly without any influence of venous reflux.

Adult↗

[Studies of meiotic origin of the extra chromosome 21 in Down syndromes detected by using (GT)n polymorphic DNA markers].

The polymorphics of two pericentric (GT)n sequences on the long arm of human chromosome 21 have been analyzed after PCR amplification, PAGE and Ag-staining for the first time in 50 Chinese Han people, and were used to detect meiotic origin of the extra chromosome 21 in Down syndromes. Six and 5 alleles were found in Chinese Han people for D21S215 and D21S120, respectively, with observed heterozygosities of 0.68 and polymorphic information content PIC, 0.67 and 0.65. For 17 Down syndromes whose parental origin of the extra chromosome 21 were known, meiotic origin of the extra chromosome 21 were determined in 16 cases, with 7 and 4 maternal meiosis I and II nondisjunction, 2 and 3 paternal meiosis I and II, respectively. The possible biological significance of the study on origin of the extra chromosome 21 has been discussed.

Chromosomes, Human, Pair 21↗

[The effect of Epstein-Barr virus gene BHRF1 expression on the apoptotic resistance of nasopharyngeal carcinoma cells].

OBJECTIVE: To investigate the effect of EB virus gene BHRF1 expression on the apoptotic resistance of nasopharyngeal carcinoma cell. METHODS: Expression vector for BHRF1 was constructed and transfected into nsaopharyngeal carcinoma cell line, CNE2. The alteration of biologic behaviour of the transfected cells was tested after 60Co radiation. RESULTS: BHRF1 expression could inhibit the expression of proliferative cell nuclear antigen, redistribute cell cycle, decrease cell sensitivity to radiation, and enhance their survival ability. CONCLUSION: It is suggested that BHRF1 expression can increase the apoptotic resistance induced by radiation.

Animals↗

[Hyperinsulinemia and insulin resistance in nondiabetic first-degree relatives of patients in familial NIDDM pedigrees].

OBJECTIVE: To study plasma insulin level and insulin sensitivity of nondiabetic first-degree relatives of patients in familial non-insulin-dependent diabetes mellitus (NIDDM) pedigrees. METHODS: Standard oral glucose tolerance test(OGTT) was conducted in 55 healthy controls and 97 first-degree relatives of NIDDM probands in familial NIDDM pedigrees. Plasma glucose and plasma insulin were determined at all phases after oral glucose load. Moreover, we calculated the glucose/insulin area ratio under the curve of OGTT (SGI) and the insulin sensitivity index (ISI) in all subjects to estimate their insulin sensitivity. RESULTS: In nondiabetic first-degree relatives, SGI and ISI were significantly decreased (P < 0.01), and plasma insulin was increased at 0, 30, 60, 120 minutes after administration of oral glucose load (P < 0.05 and P < 0.01), as compared with the controls, in matched age, body mass index (BMI) and proportion of sex. In both first-degree relatives and the insulin controls, SGI was positively correlated with ISI (r = 0.39, 0.41, respectively, P < 0.01) and both SGI and ISI were inversely correlated with BMI (r = -0.38, -0.39; -0.32, -0.25, respectively, P < 0.01). Moreover, FINS in the two groups was positively correlated with BMI (r = 0.30, 0.34, respectively, P < 0.05). CONCLUSION: In nondiabetic first-degree relatives of patients in familial NIDDM pedigrees, plasma insulin level was increased and insulin sensitivity was decreased as compared with the healthy controls. It suggests that they suffered from hyperinsulinemia and insulin resistance.

Adult↗

[The diagnosis and therapy of tinnitus].

Selection criteria for the therapeutic strategy are provided by a classification on the basis of the following points: 1. can be masked by a sound, 2. response to parenteral lidocaine. This classification was used to treat 119 patients with tinnitus. Masking is the first therapy for tinnitus. If masking had no effect, lidocaine test were undergone. The patient who has a positive response to lidocaine were treated by antiepileptic drugs. Patients with negative response to lidocaine negative were treated by suppressant. The prognosis for patients with positive masking effect was more better than the negative one. The mechanisms of tinnitus were discussed.

Anticonvulsants↗