In vivo functions of histone acetylation/deacetylation in Tup1p repression and Gcn5p activation.
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Acetylation↗
Biomedical subjects
W Zhang
Publications and source records attributed to W Zhang.
Optimally weighted wavelet transform based on supervised training for detection of microcalcifications in digital mammograms.
We are developing a computer-aided diagnosis (CAD) scheme for detection of clustered microcalcifications in digital mammograms. The use of an empirically chosen wavelet and scale combination for detection of microcalcifications as an initial step of the CAD scheme has been reported by us previously. In this study, we developed a technique for optimizing the weights at individual scales in the wavelet transform to improve the performance of our CAD scheme based on the supervised learning method. In the learning process, an error function was formulated to represent the difference between a desired output and the reconstructed image obtained from weighted wavelet coefficients for a given mammogram. The error function was then minimized by modifying the weights for wavelet coefficients by means of a conjugate gradient algorithm. The Least Asymmetric Daubechies' wavelets were optimized with 297 regions of interest (ROIs) as a training set by a jackknife method. The performance of the optimally weighted wavelets was evaluated by means of receiver-operating characteristic (ROC) analysis by use of the above set of ROIs. The analysis yielded an average area under the ROC curve of 0.92, which outperforms the difference-image technique used in our existing CAD scheme, as well as the partial reconstruction method used in our previous study.
Biophysical Phenomena↗
Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection.
Most equine infectious anemia virus (EIAV)-infected horses have acute clinical disease, but they eventually control the disease and become lifelong carriers. Cytotoxic T lymphocytes (CTL) are considered an important immune component in the control of infections with lentiviruses including EIAV, but definitive evidence for CTL in the control of disease in carrier horses is lacking. By using retroviral vector-transduced target cells expressing different Gag proteins and overlapping synthetic peptides of 16 to 25 amino acids, peptides containing at least 12 Gag CTL epitopes recognized by virus-stimulated PBMC from six long-term EIAV-infected horses were identified. All identified peptides were located within Gag matrix (p15) and capsid (p26) proteins, as no killing of target cells expressing p11 and p9 occurred. Each of the six horses had CTL recognizing at least one Gag epitope, while CTL from one horse recognized at least eight different Gag epitopes. None of the identified peptides were recognized by CTL from all six horses. Two nonamer peptide epitopes were defined from Gag p26; one (18a) was likely restricted by class I equine leukocyte alloantigen A5.1 (ELA-A5.1) molecules, and the other (28b-1) was likely restricted by ELA-A9 molecules. Sensitization of equine kidney target cells for CTLm killing required 10 nM peptide 18a and 1 nM 28b-1. The results demonstrated that diverse CTL responses against Gag epitopes were generated in long-term EIAV-infected horses and indicated that ELA-A class I molecules were responsible for the diversity of CTL epitopes recognized. This information indicates that multiple epitopes or whole proteins will be needed to induce CTL in horses with different ELA-A alleles in order to evaluate their role in controlling EIAV.
Amino Acid Sequence↗
An array of novel murine spleen focus-forming viruses that activate the erythropoietin receptor.
The Friend spleen focus-forming virus (SFFV) env gene encodes a 409-amino-acid glycoprotein with an apparent Mr of 55,000 (gp55) that binds to erythropoietin receptors (EpoR) to stimulate erythroblastosis. We reported previously the in vivo selection during serial passages in mice of several evolutionary intermediates that culminated in the formation of a novel SFFV (M. E. Hoatlin, E. Gomez-Lucia, F. Lilly, J. H. Beckstead, and D. Kabat, J. Virol. 72:3602-3609, 1998). A mouse injected with a retroviral vector in the presence of a nonpathogenic helper virus developed long-latency erythroblastosis, and subsequent viral passages resulted in more pathogenic isolates. The viruses taken from these mice converted an erythropoietin-dependent cell line (BaF3/EpoR) into factor-independent derivatives. Western blot analysis of cell extracts with an antiserum that broadly reacts with murine retroviral envelope glycoproteins suggested that the spleen from the initial mouse with mild erythoblastosis contained an array of viral components that were capable of activating EpoR. DNA sequence analysis of the viral genomes cloned from different factor-independent cell clones revealed env genes with open reading frames encoding 644, 449, and 187 amino acids. All three env genes contained 3' regions identical to that of SFFV, including a 6-bp duplication and a single-base insertion that have been shown previously to be critical for pathogenesis. However, the three env gene sequences did not contain any polytropic sequences and were divergent in their 5' regions, suggesting that they had originated by recombination and partial deletions of endogenously inherited MuLV env sequences. These results suggest that the requirements for EpoR activation by SFFV-related viruses are dependent on sequences at the 3' end of the env gene and not on the polytropic regions or on the 585-base deletions that are common among the classical strains of SFFV. Moreover, sequence analysis of the different recombinants and deletion mutants revealed that short direct and indirect repeat sequences frequently flanked the deletions that had occurred, suggesting a reverse transcriptase template jumping mechanism for this rapid retroviral diversification.
Amino Acid Sequence↗
Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: reconstitution studies in a ZAP-70-deficient Jurkat T-cell line.
T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development. However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered by the lack of a suitable T-cell model for biochemical and genetic analyses. In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driven transcription. These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells. However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation. Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells.
Clone Cells↗
Partial agonists and antagonists reveal a second permeability state of human lymphocyte P2Z/P2X7 channel.
Extracellular ATP is known to trigger apoptosis of thymocytes and lymphocytes through a P2Z receptor at which ATP is a partial agonist, giving only 70% of the maximum response of 3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate (BzATP), a full agonist. This cytolytic receptor and its associated ion channel are Ca2+ (and Ba2+) selective but also pass molecules up to the size of ethidium cation (314 Da). RT-PCR showed identity between lymphocyte P2Z and the hP2X7 gene recently cloned from human monocytes. When human leukemic B lymphocytes were incubated with ATP and 133Ba2+, an immediate influx of isotope occurred. It was augmented by 45% when ATP was added 10 min before isotope. Time-resolved flow cytometry was used to examine kinetics of ethidium uptake in cells incubated with BzATP or the partial agonists ATP, 2-methylthioadenosine 5'-triphosphate, or adenosine 5'-O-(3-thiotriphosphate). Maximally effective concentrations of BzATP (50 microM) induced immediate uptake of ethidium at a rate linear with time. In contrast, a delay was observed (30 s) before ethidium uptake commenced after addition of maximally effective ATP concentrations (500 microM) at 37 degreesC, and the delay was longer at 24 degreesC. ATP addition 2-10 min before ethidium abolished the delay. The delay was longer with other partial agonists and inversely related to maximal flux produced by agonist. A delay was also observed for submaximal BzATP concentrations (10-20 microM). P2Z/P2X7 inhibitors, KN-62 and 5-(N, N-hexamethylene)-amiloride, reduced the rate of agonist-induced ethidium uptake and lengthened the delay. The results support a model in which agonists for P2Z/P2X7 receptor mediate an immediate channel opening allowing passage of small inorganic cations, followed by a slow further permeability increase allowing passage of larger permeant cations like ethidium. The rate of the second step depends on time and temperature and the efficacy and concentration of agonist and is slowed by antagonists, suggesting it depends on the fraction of P2Z/P2X7 channels held in the initial open state.
Adenosine Triphosphate↗
Effect of chronic fluoride exposure in uremic rats.
This study was conducted to test the hypothesis that the margin of safe fluoride exposure is narrowed in rats that are physiologically compromised by renal dysfunction. The study objective was to determine whether increases in fluoride retention and tissue fluoride levels in rats with surgically induced renal insufficiency result in toxic fluoride effects not ordinarily observed in healthy animals. Uremic and sham-operated control rats received 0 microg/ml, 5 (0.26 mmol/l), 15 (0.79), or 50 microg/ml (2.63 mmol/l) of fluoride in their drinking water for 3 or 6 months. Fluoride retention was monitored, and, following euthanasia, tissue fluoride and biochemical markers of tissue function were analyzed. Selected tissues were saved for histology, and bone marrow cells were harvested for determining the frequency of sister chromatid exchange, a marker of genetic damage. In spite of significantly higher levels of fluoride in the tissues of the animals with renal insufficiency, there were no clinically adverse, fluoride-induced, extraskeletal physiological, biochemical, or genetic effects of chronic exposure to common levels of fluoride in these rats.
Animals↗
Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation.
Primary pulmonary hypertension (PPH) is a disease characterized pathologically by pulmonary artery medial hypertrophy, adventitial thickening, and neointimal proliferation. Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension.
Angiotensin Receptor Antagonists↗
Costs and utilization of substance abuse care in a privately insured population under managed care.
OBJECTIVE: Cost and utilization patterns of substance abuse and mental health treatment under private, employer-sponsored, managed behavioral health care plans were examined. METHODS: Data were from claims made in 1995 in 93 behavioral health care plans covering 617,133 members. Rates of use of mental health and substance abuse care were determined, as were payments by insurers and patients for the two types of care. Means were calculated per plan member and per user of either of these service types. RESULTS: Approximately .3 percent of plan members used any substance abuse services; 5.2 percent used mental health services. However, among substance abuse patients, average costs were more than twice as high as average costs for mental health patients. For substance abuse treatment, the annual cost per user was $2,188, compared with $979 for users of mental health care. Annual per-member costs were $6.51 for substance abuse treatment and $50.08 for mental health care. Higher costs for substance abuse treatment reflected greater rates of use of both inpatient and intensive outpatient treatment. Overall, substance abuse costs represented 13 percent of insurance payments for behavioral health care and perhaps .4 percent of the cost of health insurance overall. CONCLUSIONS: Substance abuse coverage accounts for a small fraction of insurance payments for behavioral health coverage and a very small fraction of insurance payments for both physical and behavioral health care.
Behavior Therapy↗
Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice.
The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 - exhibit distinct, but overlapping expression patterns during development of the skeletal muscle lineage and loss-of-function mutations in these genes result in different effects on muscle development. MyoD and Myf5 have been shown to act early in the myogenic lineage to establish myoblast identity, whereas myogenin acts later to control myoblast differentiation. In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal muscle, but they upregulate myogenin expression, which could potentially compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null mutations were combined suggested that these genes do not share overlapping myogenic functions in vivo. To determine whether the functions of MRF4 might overlap with those of myogenin or MyoD, we generated double mutant mice lacking MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a comparable number of residual muscle fibers to mice lacking myogenin alone and myoblasts from those double mutant mice formed differentiated multinucleated myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas mice lacking either MRF4 or MyoD were viable and did not show defects in muscle development, MRF4/MyoD double mutants displayed a severe muscle deficiency similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double mutants, indicating that myogenin is insufficient to support normal myogenesis in vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in the muscle differentiation pathway and suggest that a threshold level of myogenic bHLH factors is required to activate muscle structural genes, with this level normally being achieved by combinations of multiple myogenic bHLH factors.
Animals↗
Hemodynamics modulate pulmonary artery response to injury.
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Animals↗
Vitamin D analogs, leukemia and WAF1.
Vitamin D compounds induce differentiation of human leukemic cells and have potential for the treatment of leukemia. In this review we summarize some of the basic mechanisms underlying the action of vitamin D compounds. A variety of vitamin D analogues were synthesized until now, some of which have enhanced antileukemic activity and a decreased propensity to cause hypercalcemia. Most actions of vitamin D compounds are mediated by nuclear receptors. In vivo, vitamin D binding protein interacts with free vitamin D compounds. Both in normal and leukemic cells, vitamin D compounds cause a differentiation to monocytes and macrophages. A variety of genes are regulated by vitamin D compounds. Recently, the cell cycle inhibitory gene p21/WAF-1/CIP-1 was characterized. The expression de novo of WAF-1 in blasts of acute myelogenous leukemia is an independent factor of unfavorable prognosis. In HL-60 leukemic cells treated with vitamin D analogs, WAF-1 can be induced by nano- or picomolar concentrations of vitamin D analogs and correlates with the induction of a differentiated phenotype. When vitamin D analogs are combined in-vitro with retinoids, an irreversible differentiation is observed. Clinical trials of vitamin D analogs are indicated in the situation of minimal residual disease and in combination with standard chemotherapy.
Cell Differentiation↗
Experience in the surgical management of 82 symptomatic herniated thoracic discs and review of the literature.
OBJECT: The authors aimed to develop management strategies for the treatment of herniated thoracic discs and to define indications for selection of surgical approaches. Symptomatic thoracic discs requiring surgery are rare. Between 1971 and 1995, 71 patients with 82 herniated thoracic discs were surgically treated by the authors. The treated group included 34 men and 37 women whose ages ranged from 19 to 75 years, with a mean age of 48 years. The most common sites of disc herniation requiring surgery were from T-8 to T-11. Evidence of antecedent trauma was present in 37% of the patients. Preoperative symptoms included pain (localized, axial, or radicular) in 54 (76%) of the 71 patients, evidence of myelopathy, that is, motor impairment in 43 (61%), hyperreflexia and spasticity in 41 (58%), sensory impairment in 43 (61%), and bladder dysfunction in 17 (24%). METHODS: Radiological diagnosis for the patients in this series was accomplished by means of myelography, computerized tomography myelography, or magnetic resonance imaging. Classification of the disc location into two groups reveals that 94% were centrolateral and 6% were lateral. Evidence of calcification was present in 65% of patients, and in 7% intradural extension was noted at surgery. Ten patients (14%) were found to have multiple herniations. Four surgical approaches were used for the removal of these 82 disc herniations: transthoracic in 49 (60%), transfacet pedicle-sparing in 23 (28%), lateral extracavitary in eight (10%), and transpedicular in two (2%). Postoperative evaluation revealed improvement or resolution of pain in 47 (87%) of 54, hyperreflexia and spasticity in 39 (95%) of 41, sensory changes in 36 (84%) of 43, bowel/bladder dysfunction in 13 (76%) of 17, and motor impairment in 25 (58%) of 43. Complications occurred in a total of 12 (14.6%) of 82 discs treated surgically. Major complications were seen in three patients and included perioperative death from cardiopulmonary compromise, instability requiring further surgery, and an increase in the severity of a preoperative paraparesis. CONCLUSIONS: Review of this series, with the attendant complications, together with evaluation of several contemporary thoracic disc series, has facilitated the authors' decision-making process when considering the comprehensive management of these patients, including the selection of a surgical approach.
Adult↗
[A preliminary study on the induction of metallothionein in rats with aluminum administration by different ways].
OBJECTIVE: To study the inductive effects of aluminum (Al) on metallothioneine (MT) in rats. METHODS: Inductive experiment of MT was conducted with Al administration in 16 SD rats, divided into trial and control groups, for two weeks by subcutaneous injection and gastric tube. RESULTS: Al could induce liver MT in the rats, to certain extent, especially more significantly by subcutaneous injection than by oral administration of Al. Oral administration of Al also could induce MT in the small intestine. Induction of MT by Al reflected the body response to stress, the metal poison Al. CONCLUSION: It postulated that combination of Al with MT was unstable due to its chemical property, so, its detoxication effect was uncertain. In addition, induction of MT in different sites, such as liver and small intestine, by Al could influence the normal metabolism of metal elements, such as zinc, etc.
Aluminum↗
[The treatment of fracture of patella by internal fixation with tension band from musculofascial tendon].
In the study of the efficacy of internal fixation with tension band of musculofascial tendon in the treatment of fracture of patella, 52 cases were reported. After a following-up of 6 months to 13 months the bone healing was observed, in 7.5 weeks in average, and the function of the knee joint had recovered to normal or almost normal. It was concluded that the treatment of fracture of patella by internal fixation with tension band from musculofascial tendon was a ideal and practicable method.
Adult↗
[A new method to repair artery injuries in extremities by phleboplasty of branched vein graft].
In order to develope a new method to overcome the difficulties in anastomosis of blood vessels with different diameter, phleboplasty was utilized at the join-point to expand the diameter of branched vein graft, with a funnel-shaped stoma formed consequently. After successfully experimented in fresh blood vessels in vitro, the method was practised clinically to repair injured arteries in extremities, with the outcome that phleboplasty of branched vein graft could enlarge the diameter by 1-1.25 times, and with satisfied effects in 3 clinic cases. So, the conclusion was that: phleboplasty of branched vein graft was a new effective and convinient method to repair injured arteries with different diameters.
Adult↗
[Parkinson's disease and dementia].
Neuropsychological tests were carried out in 30 patients with Parkinson's disease and 26 healthy controls. The results showed that the average scores of HRB(A)-RC test were above the limited scores, 45.45%-86.36% cases being over the limited scores (P < 0.01), except speech sound perception test. Damage degrees (DQ) from the least to the most serious were 63.64%. WAIS-RC test and WMS test showed that the average scores of IQ and MQ in patients were lower than those in the normal. The difference of IQ, MQ scores between patients and controls was very significant (P < 0.01). The damaged cases of IQ, MQ from the least to the most serious were 20% and 60%, respectively. This indicated that the patients with Parkinson's disease were obviously damaged in intelligence and memory. In this article, there were 6 cases (20%) fitted the diagnostic standard of dementia, among them, 4 were subcortical dementia and 2 cases were complex dementia. We found that the differences between the course and IQ, MQ were very significant (P < 0.05), but not between the course and DQ. It is implied that in the very early stage, the patients could appear abnormal in neuropsychology, and the intelligence and memory may be damaged more seriously in longer course. The result suggests that the early diagnosis and prompt intervention is important to prevent the occurrence and advance of dementia.
Aged↗