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A Chen

Publications and source records attributed to A Chen.

At least 145 records · Page 8Linked to original sources
PubMed2000

Cross-linking of cell surface receptors enhances cooperativity of molecular adhesion.

Cooperativity of molecular adhesion has been proposed as a mechanism for enhanced binding strength of adhesion molecules on the cell surface. Direct evidence for its mechanism, however, has been lacking until now. Atomic force microscopy (AFM) was used to measure the adhesive strength between concanavalin A (Con A) coupled to an AFM tip and Con A receptors on the surface of NIH3T3 fibroblast cells. Cross-linking of receptors with either glutaraldehyde or 3, 3'-dithio-bis(sulfosuccinimidylproprionate) (DTSSP) led to an increase in adhesion that could be attributed to enhanced cooperativity among adhesion complexes. An increase in loading rate due to greater stiffness of fixed cells also contributed to the twofold increase in binding strength. These results show that receptor cross-linking can greatly contribute to a total increase in cell adhesion by creating a shift toward cooperative binding of receptors.

3T3 Cells↗
PubMed2000

In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain.

CD23, the low affinity receptor for IgE (FcvarepsilonRII), is involved in regulation of IgE synthesis by B-lymphocytes. Five monoclonal antibodies to human CD23 were generated from cynomolgus macaques immunized with purified soluble CD23 (sCD23). Four of the five primate antibodies blocked the binding of IgE complexes to CD23 positive cells and also inhibited the production of IgE in vitro by IL-4 induced human peripheral blood mononuclear cells (PBMC). The variable domains of several primate antibodies were utilized to construct chimeric macaque/human (PRIMATIZED((R))) monoclonal antibodies. PRIMATIZED((R)) p5E8G1, containing human gamma 1 constant region, inhibited IgE production in vitro as efficiently as the parent primate antibody, but the human gamma 4 constant version, PRIMATIZED((R)) p5E8G4, was not as effective in IgE inhibition. An F(ab')(2) of p5E8G1 did not inhibit IgE production but did interfere with IgE inhibition by the intact anti-CD23 antibody in a dose dependent fashion. The murine monoclonal antibody MHM6 recognizes human CD23 at a different epitope than primate antibody 5E8, and inhibits IgE production by IL-4 induced PBMC. As with the F(ab')(2) of p5E8G1, the F(ab')(2) of MHM6 also failed to inhibit IgE production. These data imply that the mechanism by which anti-CD23 antibodies inhibit IgE production requires cross-linking of CD23 to an IgG receptor. These data also imply that neither bivalent cross-linking of CD23 alone or inhibition of CD23 binding to its natural ligands is sufficient to inhibit IgE production.

Animals↗
PubMed2000

SPEEDY: spin-echo enhanced diffusion filtered spectroscopy. A new tool for high resolution MAS NMR

The pulsed field gradient diffusion edited experiment, bipolar LED, has been combined with the Carr-Purcell-Meiboom-Gill (CPMG) spin-echo sequence for the analysis of solid phase resin samples. Spin-echo enhanced diffusion filtered spectroscopy (SPEEDY), when optimized, filters both the compounds that demonstrate fast diffusion rates as well as the compounds that demonstrate fast T(2) relaxation rates. Using this technique, compounds that are not covalently attached to the resin are not observed and contributions from the resin matrix are greatly attenuated. The interpretation of the resulting spectrum is more readily accessible. This technique lessens the importance of completely removing reaction residues or the wash solvents simply for analytical evaluation. The utility of the combined filtering scheme was demonstrated by the implementation into a NOESY sequence.

Journal Article↗
PubMed2000

Identification of two subtypes of infantile acid maltase deficiency.

Infantile patients with acid maltase deficiency have severe hypertrophic cardiomyopathy, left ventricular outflow obstruction, and generalized muscle weakness and die before 1 year of age. We identified 12 infants with acid maltase deficiency who had a similar clinical presentation but less severe cardiomyopathy and absence of left ventricular outflow obstruction, and 9 of 12 had longer survival with assisted ventilation and supplemental intubation.

Age of Onset↗
PubMed2000

Neuroimaging variables related to development of Secondary Attention Deficit Hyperactivity Disorder after closed head injury in children and adolescents.

OBJECTIVE: To characterize children who develop Secondary Attention Deficit Hyperactivity Disorder (S-ADHD) after severe and moderate closed head injury (CHI) according to neuroimaging variables. METHOD: Ninety-nine children from 4-19 years who suffered severe and moderate CHI were prospectively followed for a year after injury. Premorbid psychiatric status was determined by administration to the parent of a structured psychiatric interview. This interview was readministered 1 year after injury to determine the presence of post-closed head injury S-ADHD. An MRI was performed 3 months after injury to define lesion locations and volumes. RESULTS: A set of multiple logistic regression models determined that the odds of developing S-ADHD were 3.64 times higher among children with thalamus injury, and 3.15 times higher among children with basal ganglia injury. There was no significant difference in lesion volumes in any of the locations of interest between the group who developed S-ADHD and the group who did not develop S-ADHD. CONCLUSION: The data support an association between S-ADHD and injury in either or both the thalamus and basal ganglia, but they do not definitively demonstrate whether injury in either structure has an effect on S-ADHD in the absence of injury in the other.

Adolescent↗
PubMed2000

Anterior ischemic optic neuropathy: a complication after systemic inflammatory response syndrome.

BACKGROUND: Patients are surviving previously fatal injuries. Unique morbidities are occurring in these survivors. Anterior ischemic optic neuropathy represents a previously unrecognized cause of blindness in the trauma victim. We hypothesize that this phenomenon is caused by unique characteristics of optic edema/ pressure or decreased blood flow associated with massive resuscitation. METHODS: Between November of 1991 and August of 1998, there were 18,199 admissions to our trauma center. Of this group, 350 patients required massive volume resuscitation (>20 liters infused over first 24 hours). Patients having closed head injuries, facial fractures or direct orbital trauma were excluded from study. The following variables were studied: demographics, injury severity (Injury Severity Score, highest lactate, worst base deficit, and lowest pH) crystalloid and transfusion requirements, ventilator requirements (PEEP) RESULTS: Of the 350 patients with massive resuscitation, 9 patients were diagnosed with anterior ischemic optic neuropathy (2.6%). Of these, seven patients required celiotomy (78%). Six of the seven celiotomy patients had damage control celiotomies and abdominal compartment syndrome (86%). One patient had a repair of a subclavian artery; one had a complex acetabular repair. Blindness was unilateral in five patients and bilateral in four. All nine patients had evidence of global hypoperfusion, systemic inflammatory response, massive resuscitation, and high ventilatory support; one patient required cardiopulmonary resuscitation. CONCLUSION: Prone positioning is known to be associated with an increased intraocular pressure. We postulate that the combination of massive resuscitation and prone positioning will increase the incidence of anterior ischemic optic neuropathy. As such, we recommend that prone positioning for adult respiratory distress syndrome be reserved for only those patients at risk of death.

Adolescent↗
PubMed2000

Fluorescent in situ hybridizaton evaluation of p53 gene deletions at a tumor interface of lingual carcinoma.

OBJECTIVE/HYPOTHESIS: To evaluate the ability of fluorescent in situ hybridization (FISH) to detect malignant cells missed by standard histological assessment at an interface between malignant and normal tissue in lingual squamous cell carcinoma (SCC) and to correlate findings of FISH assessment with patients' clinical stages. STUDY DESIGN: Retrospective assessment of archival tissue from 31 patients with lingual SCC treated at University of Wisconsin Hospital and Clinics in Madison. METHODS: An assay combining standard histological and FISH techniques was used to assess a tumor interface tissue section and allow identification of each tumor's ploidy characteristics and p53 gene deletions and the presence or absence of malignant cells within tissue viewed as "normal" on histological review. RESULTS: Forty-five percent of tumors (14 of 31) demonstrated ploidy changes and 84% (26 of 31) showed p53 deletions. Of these 26 tumors with p53 deletions, 14 were found to have "microfoci" with p53 deletions within tissue that appeared normal on histological examination. These microfoci were found in 75% of late-stage tumors and in only 35% of early-stage tumors. CONCLUSIONS: FISH allowed identification of malignant cells in tissue viewed as normal on standard histological assessment, and this finding occurred more frequently in late-stage tumors.

Adult↗
PubMed2000

Terbutaline prevents circulatory failure and mitigates mortality in rodents with endotoxemia.

Septic shock is characterized by a decrease in systemic vascular resistance. Nevertheless, regional increases in vascular resistance can occur that may predispose mammals to organ dysfunction, including the acute respiratory distress syndrome. In the host infected by endotoxin (lipopolysaccharide, LPS), the expression and release of proinflammatory tumor necrosis factor-alpha (TNFalpha) rapidly increases, and this cytokine production is regulated by agents elevating cyclic AMP. In this report, we present evidence that terbutaline, a beta2-agonist, inhibits TNFalpha production and enhances interleukin-10 (IL-10) release in the anesthetized rat treated with LPS. In addition, an overproduction of nitric oxide (NO, examined by its metabolites nitrite/nitrate) by inducible NO synthase (iNOS, examined by western blot analysis) is attenuated by pretreatment of LPS rats with terbutaline. Overall, pretreatment of rats with terbutaline attenuates the delayed hypotension and prevents vascular hyporeactivity to norepinephrine. In addition, pretreatment of mice with terbutaline also improves the survival in a model of severe endotoxemia. The infiltration of polymorphonuclear neutrophils into organs (e.g., lung and liver) from the surviving LPS mice treated with terbutaline was reduced almost to that seen in the normal controls. These findings suggest that the inhibition of TNFalpha and NO (via iNOS) production as well as the increment of IL-10 production contribute to the beneficial effect of terbutaline in animals with endotoxic shock.

Acetylcholine↗
PubMed2000

The SCF(HOS/beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct domains within CUL1 for substrate targeting and ubiquitin ligation.

We describe a purified ubiquitination system capable of rapidly catalyzing the covalent linkage of polyubiquitin chains onto a model substrate, phosphorylated IkappaBalpha. The initial ubiquitin transfer and subsequent polymerization steps of this reaction require the coordinated action of Cdc34 and the SCF(HOS/beta-TRCP)-ROC1 E3 ligase complex, comprised of four subunits (Skp1, cullin 1 [CUL1], HOS/beta-TRCP, and ROC1). Deletion analysis reveals that the N terminus of CUL1 is both necessary and sufficient for binding Skp1 but is devoid of ROC1-binding activity and, hence, is inactive in catalyzing ubiquitin ligation. Consistent with this, introduction of the N-terminal CUL1 polypeptide into cells blocks the tumor necrosis factor alpha-induced and SCF-mediated degradation of IkappaB by forming catalytically inactive complexes lacking ROC1. In contrast, the C terminus of CUL1 alone interacts with ROC1 through a region containing the cullin consensus domain, to form a complex fully active in supporting ubiquitin polymerization. These results suggest the mode of action of SCF-ROC1, where CUL1 serves as a dual-function molecule that recruits an F-box protein for substrate targeting through Skp1 at its N terminus, while the C terminus of CUL1 binds ROC1 to assemble a core ubiquitin ligase.

Anaphase-Promoting Complex-Cyclosome↗
PubMed2000

The DNA binding protein BTEB mediates acetaldehyde-induced, jun N-terminal kinase-dependent alphaI(I) collagen gene expression in rat hepatic stellate cells.

Alcohol-induced cirrhosis results partially from the excessive production of collagen matrix proteins, which, predominantly alphaI(I) collagen, are produced and secreted by activated hepatic stellate cells (HSC). The accumulation of alphaI(I) collagen in HSC during cirrhosis is largely due to an increase in alphaI(I) collagen gene expression. Acetaldehyde, the major active metabolite of alcohol, is known to stimulate alphaI(I) collagen production in HSC. However, the mechanisms responsible for it remain unknown. The aim of this study was to elucidate the mechanisms by which alphaI(I) collagen gene expression is induced by acetaldehyde in rat HSC. In the present study, the acetaldehyde response element was located in a distal GC box, previously described as the UV response element, in the promoter of the alphaI(I) collagen gene (-1484 to -1476). The GC box was predominantly bound by the DNA binding transcription factor BTEB (basic transcription element binding protein), expression of which was acetaldehyde and UV inducible. Blocking BTEB protein expression significantly reduced the steady-state levels of the acetaldehyde-induced alphaI(I) collagen mRNA, suggesting that BTEB is required for this gene expression. Further studies found that acetaldehyde activated Jun N-terminal kinase (JNK) 1 and 2 and activator protein 1 (AP-1) transactivating activity. Inhibition of JNK activation resulted in the reduction of the acetaldehyde-induced BTEB protein abundance and alphaI(I) collagen mRNA levels, indicating that the expression of both genes is JNK dependent in HSC. Taken together, these studies demonstrate that BTEB mediates acetaldehyde-induced, JNK-dependent alphaI(I) collagen gene expression in HSC.

Acetaldehyde↗
PubMed2000

Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron protein regulated with kidney ischemia.

Mxi2 is one of three known alternative spliced forms of the stress-activated mitogen-activated protein kinase p38 (CSBP). Mxi2 was originally identified as a Max-interacting protein and is the smallest member of the family of stress-activated kinases isolated to date. Mxi2 lacks most of the XI domain found in p38 and instead has a distinct COOH-terminal sequence of 17 amino acids. Here we present the genomic structure of the Mxi2/p38 locus on human chromosome 6q21.2/21.3 and establish the origin of the three spliced forms of p38. Using Mxi2-specific antibodies in mouse organs, we found the Mxi2 protein to be present exclusively in the kidney. Mxi2 is present predominantly in the distal tubule of the nephron and the level of the protein decreased during kidney ischemia-reperfusion. Stress signals or other known activators of the p38 pathway including MAP kinase-kinase 3 and MAP kinase-kinase 6 did not induce the kinase activity of Mxi2 using ATF-2 as a substrate. With the use of hybrid proteins encoding different portions of Mxi2 and p38 polypeptides, the different properties of Mxi2 can be assigned to its unique COOH terminus.

Amino Acid Sequence↗
PubMed2000

Conformational modulation of slow skeletal muscle troponin T by an NH(2)-terminal metal-binding extension.

Troponin T (TnT) is an essential element in the thin filament Ca(2+)-regulatory system controlling striated muscle contraction. Alternative RNA splicing generates developmental and muscle type-specific TnT isoforms differing in the hypervariable NH(2)-terminal region. Using avian fast skeletal muscle TnT containing a metal-binding segment, we have demonstrated a role of the NH(2)-terminal domain in modulating the conformation of TnT (Wang J and Jin JP. Biochemistry 37: 14519-14528, 1998). To further investigate the structure-function relationship of TnT, the present study constructed and characterized a recombinant protein in which the metal-binding peptide present in avian fast skeletal muscle TnT was fused to the NH(2) terminus of mouse slow skeletal muscle TnT. Metal ion or monoclonal antibody binding to the NH(2)-terminal extension induced conformational changes in other domains of the model TnT molecule. This was shown by the altered affinity to a monoclonal antibody against the COOH-terminal region and a polyclonal antiserum recognizing multiple epitopes. Protein binding assays showed that metal binding to the NH(2)-terminal extension had effects on the interaction of TnT with troponin I, troponin C, and most significantly, tropomyosin. The data indicate that the NH(2)-terminal Tx [4-7 repeats of a sequence motif His-(Glu/Ala)-Glu-Ala-His] extension confers a specific conformational modulation in the slow skeletal muscle TnT.

Animals↗
PubMed2000

The role of AHA motifs in the activator function of tomato heat stress transcription factors HsfA1 and HsfA2.

Using reporter assays in tobacco protoplasts and yeast, we investigated the function of the acidic C-terminal activation domains of tomato heat stress transcription factors HsfA1 and HsfA2. Both transcription factors contain short, essential peptide motifs with a characteristic pattern of aromatic and large hydrophobic amino acid residues embedded in an acidic context (AHA motifs). The prototype is the AHA1 motif of HsfA2, which has the sequence DDIWEELL. Our mutational analysis supports the important role of the aromatic and large hydrophobic amino acid residues in the core positions of the AHA motifs. The pattern suggests the formation of an amphipathic, negatively charged helix as the putative contact region with components of the basal transcription complex. In support of this concept, proline or positively charged residues in or adjacent to the AHA motifs markedly reduce or abolish their activity. Both AHA motifs of HsfA1 and HsfA2 contribute to activator potential, and they can substitute for each other; however, there is evidence for sequence and positional specificity.

Amino Acid Motifs↗
PubMed2000

[Analysis of pragmatic aspects of communication behavior of verbal and nonverbal autistic children].

The analysis and intervention of communication is an important focus of autism research. The present study is a microanalysis of the communicative behaviour of 10 autistic children with their parents and a therapist. Protests, appropriate initiation and responses of the children were analysed in relation to demands and the specific feedback of the adults. After 20 months of structured therapy changes in the communicative behaviour of the participants were demonstrated. Autistic children showed different communicative pattern with their parents compared to a therapist. The non-verbal group exhibited significantly more protests and decreased responsivity with their parents compared to the therapist. The verbal group interacted with their parents predominantly by echolalia. After 20 months a significant reduction in protests, increased compliance and responsivity were obvious in the non-verbal group. The verbal group showed a reduction in echolalia as well as increased responsive and spontaneous communication. The results demonstrate that even non-verbal autistic children are sensitive towards different interaction partners. Over the observation period participants showed a reduction in behaviour problems and positive developments of communicative behaviour.

Adult↗
PubMed2000

Pretreatment prostate-specific antigen and Gleason score predict the risk of extracapsular extension and the risk of failure following radiotherapy in patients with clinically localized prostate cancer.

The purpose of this study is to evaluate the use of a relatively simple equation for predicting the risk of extracapsular extension (ECE) based on the pretreatment prostate-specific antigen (PSA) and Gleason score (GS) in patients with clinically localized prostate cancer. Three hundred and seventy-four patients who underwent radical prostatectomy between 1988 and 1994 and 521 men undergoing definitive radiotherapy during a similar time period were eligible for this analysis. Surgically treated patients were considered eligible if the pathological stage, preoperative PSA, and GS were available. Among these patients, the median preoperative PSA was 8.1 ng/mL (range, 0 to 195 ng/mL), and the median preoperative GS was 6 (range, 2 to 10). The empirically derived equation tested was (1.5 x PSA + [GS - 3] x 10). For this equation, the range of calculated risk was limited to 0% to 100%. Using the empirically derived equation, patients with a low calculated risk (CR) of < or = 33% had an average calculated risk (ACR) of 21.9% and an observed incidence (OI) of ECE was 17.8%. Patients with a moderate CR of 34% to 66% had an ACR of 46.3%, and an OI of ECE was 46.7%. Patients with a CR of 67% to 100% had an ACR of 83.7% and an OI of ECE of 66.7%. Of the 21 patients who had a PSA < or = 4 and a GS < or = 4, only 1 patient (4.8%) was found to have ECE. Men with an estimated risk of ECE of <33%, 33% to 67%, and >67% had a 4-year risk of biochemical failure following radiotherapy of 29%, 56%, and 78% (P < .00001). This empirically derived data appears to be reasonably accurate at estimating the incidence of ECE in patients with at low or intermediate risk before surgery. The risk of biochemical failure following radiotherapy also correlated the risk of ECE. Future staging systems for prostate cancer should use similar approach for defining risk groups.

Biopsy↗
PubMed2000

Malignant meningioma with rhabdoid transformation.

We report a rare case of recurrent meningioma with malignant change and rhabdoid transformation in a 54-year-old woman who presented with severe headache and progressive weakness of the right extremities. The patient had a history of atypical meningioma and had undergone a craniotomy to remove a tumor nine years earlier. We discuss the distinctive morphologic, immunohistochemical staining and ultrastructural features of a recurrent malignant meningioma. A meningioma with rhabdoid transformation may indicate aggressive biologic and clinical behavior of the tumor.

Female↗
PubMed2000

Effect of batroxobin on expression of c-Jun in left temporal ischemic rats with spatial learning and memory disorder.

The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.

Animals↗