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Biomedical subjects

J Xie

Publications and source records attributed to J Xie.

At least 145 records · Page 8Linked to original sources

Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns.

BACKGROUND: Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. METHODS: We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. FINDINGS: All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. INTERPRETATION: rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.

Administration, Cutaneous↗

Human hematopoietic cell specific nuclear protein MNDA interacts with the multifunctional transcription factor YY1 and stimulates YY1 DNA binding.

The human myeloid nuclear differentiation antigen, MNDA, is expressed only in myelomonocytic and a subset of B lymphoid hematopoietic cells. MNDA is uniformly distributed throughout the interphase cell nucleus and associates with chromatin, but does not bind specific DNA sequences. We recently demonstrated that MNDA binds nucleolin and nucleophosmin/NPM/B23 and both of these nuclear proteins bind the ubiquitous zinc finger transcription factor YY1. Investigations of the possible effect of MNDA on the interaction between YY1 and NPM, showed that MNDA bound YY1 directly under both in vitro and in vivo conditions. The MNDA-YY1 interaction enhanced the affinity of YY1 for its target DNA and decreased its rate of dissociation. The N-terminal half (200 amino acids) of MNDA was sufficient for maximum enhancement of YY1 DNA binding and a portion of this sequence was responsible for binding YY1. MNDA participated in a ternary complex with YY1 and the YY1 target DNA element. The results show that MNDA affects the ability of YY1 to bind its target DNA sequnce and that MNDA participates in a ternary complex possibly acting as a cofactor to impart lineage specific features to YY1 function.

Antigens, Differentiation, Myelomonocytic↗

A study of sexual behavior among rural residents of China.

OBJECTIVE: Although the recent spread of HIV/AIDS and other sexually transmitted diseases (STDs) in China has been associated with sexual activities, little information has been available about sexual behavior in rural areas with high HIV prevalence. Studies identifying high-risk sexual behaviors are needed to formulate effective prevention programs. METHODS: A cross-sectional study design was used to measure sexual activities using a two-stage cluster sampling method. A two-part anonymous questionnaire was used. Sensitive questions related to sexual behavior were administered using a tape recorder, earphones, and an answer sheet which did not include the text. RESULTS: In total, 1057 subjects were interviewed. Among 886 sexually active individuals, 7.8% had >1 sexual partner, 22.8% had premarital sex, 2.4% had anal intercourse, 4.1% had oral intercourse, and 2.3% had both anal and oral intercourse. Less than 2% reported past or current sexually transmitted diseases. Overall, 10.4% used condoms; only 11.2% for every sexual act. History of premarital and extramarital sex was higher in younger people. CONCLUSIONS: Sexual norms in rural China are changing rapidly and high-risk sexual behavior among young rural residents is increasing. Strategies to prevent HIV/AIDS should include education to promote delayed onset of sexual activity, safer sexual behavior, and condom use.

Adolescent↗

Identification of a large Myc-binding protein that contains RCC1-like repeats.

The protooncogene MYC plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis and has been implicated in a variety of human tumors. MYC and the closely related MYCN encode highly conserved nuclear phosphoproteins (Myc and NMyc) that apparently function as transcription factors in the cell. We have identified a large and highly conserved nuclear protein that interacts directly with the transcriptional activating domain of Myc (designated "protein associated with Myc" or Pam). Pam contains an extended amino acid sequence with similarities to a protein known as regulator of chromosome condensation (RCC1), which may play a role in the function of chromatin. The gene encoding Pam (PAM) is expressed in all of the human tissue examined, but expression is exceptionally abundant in brain and thymus. Pam binds specifically to Myc, but not NMyc. The region in Myc required for binding to Pam includes a domain that is essential for the function of Myc and that is frequently mutated in Burkitt's lymphomas. PAM is located within a 300-kb region on chromosome 13q22.

Adaptor Proteins, Signal Transducing↗

[G6PD gene mutations in Guangxi, China].

OBJECTIVE: Fifty-six G6PD-deficient male individuals of the Guangxi origin were investigated at the molecular level to understand the basis of G6PD deficiency. METHODS: PCR amplified the exons 2,5,6,7,8, 10,11,12 and 13 of the G6PD gene respectively, combined with ASO dot blot hybridization and restriction enzymes digestion methods to screen 10 common Chinese G6PD mutations. RESULTS: Six mutations were detected, namely cDNA1376(G-->T)(25.0%), cDNA1388(G-->A)(16.1%), cDNA95(A-->G)(19.8%), cDNA592 (C-->T)(7.1%), cDNA1024(C-->T)(1.8%) and cDNA392(G-->T) (1.8%). The unknown mutations accounted for 28.6%. cDNA1311(C-->T),cDNA1360(C-->T),cDNA835(A-->T), cDNA493(A-->G) and cDNA487(G-->A) were not discovered among the cases. CONCLUSION: The findings may provide some useful informations for physician scientists to get insight into the pathogenesis of G6PD deficiency so as to improve clinical diagnosis, prevention and cure of G6PD deficiency. The results may be of significance in anthropology and geneties as well.

Glucosephosphate Dehydrogenase↗

Progression through the spliceosome cycle requires Prp38p function for U4/U6 snRNA dissociation.

The elaborate and energy-intensive spliceosome assembly pathway belies the seemingly simple chemistry of pre-mRNA splicing. Prp38p was previously identified as a protein required in vivo and in vitro for the first pre-mRNA cleavage reaction catalyzed by the spliceosome. Here we show that Prp38p is a unique component of the U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) particle and is necessary for an essential step late in spliceosome maturation. Without Prp38p activity spliceosomes form, but arrest in a catalytically impaired state. Functional spliceosomes shed U4 snRNA before 5' splice-site cleavage. In contrast, Prp38p-defective spliceosomes retain U4 snRNA bound to its U6 snRNA base-pairing partner. Prp38p is the first tri-snRNP-specific protein shown to be dispensable for assembly, but required for conformational changes which lead to catalytic activation of the spliceosome.

Fungal Proteins↗

Control of alternative splicing of potassium channels by stress hormones.

Many molecular mechanisms for neural adaptation to stress remain unknown. Expression of alternative splice variants of Slo, a gene encoding calcium- and voltage-activated potassium channels, was measured in rat adrenal chromaffin tissue from normal and hypophysectomized animals. Hypophysectomy triggered an abrupt decrease in the proportion of Slo transcripts containing a "STREX" exon. The decrease was prevented by adrenocorticotropic hormone injections. In Xenopus oocytes, STREX variants produced channels with functional properties associated with enhanced repetitive firing. Thus, the hormonal stress axis is likely to control the excitable properties of epinephrine-secreting cells by regulating alternative splicing of Slo messenger RNA.

Adrenal Medulla↗

Selective pituitary resistance to thyroid hormone produced by expression of a mutant thyroid hormone receptor beta gene in the pituitary gland of transgenic mice.

Resistance to thyroid hormone (RTH) has been subdivided into generalized resistance (GRTH) and pituitary resistance (PRTH) based on the clinical impression of absence or presence of thyrotoxicosis. However, due to lack of objective clinical and genetic criteria, the existence of PRTH as a distinct entity became controversial. To determine what the phenotype would be if RTH was confined to the pituitary, a transgenic mouse was developed in which expression of the mutant thyroid hormone receptor (TR) beta (G345R) was targeted to the pituitary thyrotrophs by placing it downstream of the mouse thyrotropin beta promoter. This construct exhibited an antagonistic effect on the thyroid hormone-dependent transactivation, mediated through the wild-type TRbeta1, only when cotransfected with the thyrotroph embryonic factor in a heterologous cell line. As expected the transgene was transcribed predominantly in the pituitary gland but not in liver. These mice showed a significant, though modest, increase in serum T4 concentration. A decrease in the serum cholesterol was observed in keeping with the selective tissue hyposensitivity to thyroid hormone.

Animals↗

Activating Smoothened mutations in sporadic basal-cell carcinoma.

Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.

Adenovirus E1A Proteins↗

Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation.

The recent resurgent interest in functional surgery for the treatment of Parkinson's disease (PD) has focused on the effects on akinesia and levodopa-induced dyskinesia. Stimulation of the subthalamic nucleus (STN) improves akinesia and rigidity but its effects on tremor have not been studied. The objective of this study was to assess the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad with motor fluctuations. Of 27 consecutive patients with STN stimulation (26 bilateral), 15 exhibited tremor rated at least 2/4 according to item 20 (rest tremor) of the Unified Parkinson's Disease Rating Scale (UPDRS) in at least one limb. The mean preoperative tremor score was 11.3+/-5.6 in off-drug and 1.2+/-2.4 in on-drug conditions. The postoperative tremor scores at the last follow up (from 1-12 months) were 2.2+/-2.2 off-drug/on-stimulation and 0.2+/-0.4 on-drug/on-stimulation. Both rest and action tremors were improved in all patients. The UPDRS tremor score was reduced by 80%, rigidity score by 65%, and akinesia score by 51% on average. For the three symptoms, the stimulation effect was close to that induced before surgery by a suprathreshold dose of levodopa given in the morning. STN stimulation can be considered an interesting alternative to thalamic or internal pallidal surgery even in PD patients with severe high-amplitude tremor. In keeping with electrophysiological data in monkeys rendered parkinsonian by MPTP injections, our results emphasize the importance of the oscillation of a neuronal loop involving the STN in the pathophysiology of parkinsonian tremor.

Adult↗

TACHY: an expert system for the management of supraventricular tachycardia in the elderly.

PURPOSE: Many physicians find the management of supraventricular tachyarrhythmia (SVT) in the elderly complex and challenging. With the use of artificial intelligence theory, we developed an interactive computer expert system, TACHY, to recommend therapies and warn physicians of potential therapeutic side effects. METHODS: We developed a knowledge base that stores guidelines for the management of SVT in the elderly. After the diagnosis of current SVT was input into the computer, TACHY generated a list of therapeutic options as hypotheses. TACHY then prompted the user to provide current patient-specific clinical information, and the optimal therapeutic option was then selected. Potential therapeutic side effects were also displayed. TACHY was tested in a retrospective and a prospective study. The retrospective study, comprising 96 patients with 126 episodes of SVT, was performed to determine the concordance of therapy between TACHY and cardiologists. A prospective study in 18 patients with 26 episodes of SVT was also performed to validate TACHY's recommendations in restoring sinus rhythm. RESULTS: In the retrospective study the concordance between TACHY and the cardiologist's first therapeutic option was 95.9% (121 of 126 episodes). In the prospective study sinus rhythm was restored in 18 (69%) of 26 episodes of SVT by the first therapeutic option recommended by TACHY. In the remaining eight episodes use of the second or third suggestion of TACHY was successful in controlling the ventricular response to SVT. No adverse reaction to the therapeutic options suggested by TACHY occurred. CONCLUSION: TACHY, a knowledge-based computer expert system that simulates human decision making, produced promising results in the management of SVT in the elderly.

Aged↗

The Finnish follicle-stimulating hormone receptor gene mutation is rare in North American women with 46,XX ovarian failure.

OBJECTIVE: To determine whether FSH receptor gene missense mutation in Finnish women with premature ovarian failure (POF) is present in North American women with POF. DESIGN: Analysis of DNA from patients and controls. PATIENT(S): Thirty-five women with POF and ten normal controls. INTERVENTION(S): Extraction of DNA with subsequent digestion by the enzyme BsmI, polyacrylamide gel electrophoresis, ethidium bromide staining, and photography. MAIN OUTCOME MEASURE(S): After restriction enzyme digestion, the frequencies of the normal allele (two fragments of 51 and 27 base pairs) and the mutant allele (a single 78-base pair fragment) were determined. RESULT(S): BsmI digestion was noted for all 35 affected individuals and 10 controls, thus demonstrating homozygosity for the normal FSH receptor allele. No patient or control was heterozygous or homozygous for the mutant allele. CONCLUSION(S): The missense mutation in the human FSH receptor gene in Finnish women with POF is uncommon in North American women with POF. The molecular basis of ovarian failure for most patients remains unknown.

Adolescent↗

Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease.

Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.

Alzheimer Disease↗

Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome.

Mutations in PATCHED (PTC), the human homolog of the Drosophila patched gene, have been identified in most exons of the gene in patients with the basal cell nevus syndrome and in sporadic basal cell carcinomas. We have screened the 23 PTC exons for mutations using single strand conformation polymorphism analysis of DNA from 86 basal cell nevus syndrome probands, 26 sporadic basal cell carcinomas, and seven basal cell nevus syndrome-associated basal cell carcinomas. This screen identified mutations located in eight exons in 13 of the basal cell nevus syndrome patients and in three of the tumors. The most common mutations were frameshifts resulting in premature chain termination. These results provide further evidence for the crucial role of PTC as a tumor suppressor in human keratinocytes.

Amino Acid Substitution↗

Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease.

The aim of this study was to compare, retrospectively, the value of chronic bilateral stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) in patients with young onset Parkinson's disease. We selected 13 consecutive patients with similar characteristics at the time of surgery: age at onset < 40 years, disabling motor fluctuations (Hoehn and Yahr stage 4 or 5 in off-drug phases) and levodopa-induced dyskinesias (LID). Eight patients were operated on in the STN and five in the GPi. The Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a LID scale were compared in on- and off-drug conditions before surgery and 6 months after surgery on stimulation using the chronic electrical parameters found to improve best the motor state of the individual patient, without adverse effects. In off-drug phases, the motor score of the UPDRS was improved by 71% with STN stimulation and by 39% with GPi stimulation on average. This difference was statistically significant (P < 0.05). Whereas rigidity and tremor showed good improvement in both groups, the decrease in the akinesia score was more pronounced in the STN group. In the STN group, the improvement of all motor symptoms was very close, or equal, to the best levodopa response. Thus the levodopa test was predictive of outcome. The improvement in off-drug period motor handicap allowed a decrease in the levodopa-equivalent dose only in the STN group (-56%). The voltage, frequency and pulse width used for chronic stimulation were lower in the STN group. In the on-drug phases there was a marked improvement in LID in the GPi group, as measured by the dyskinesias score during an acute levodopa test, whereas there was only a small decrease in the STN group (P < 0.05). However, in the long term, the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in the GPi group during activities of everyday life. In conclusion, the overall results favour the neurosurgical treatment of Parkinson's disease by stimulating the STN rather than the GPi.

Adult↗

Transcriptional regulation of the SMK1 mitogen-activated protein kinase gene during meiotic development in Saccharomyces cerevisiae.

Meiotic development (sporulation) in Saccharomyces cerevisiae is characterized by an ordered pattern of gene expression, with sporulation-specific genes classified as early, middle, mid-late, or late depending on when they are expressed. SMK1 encodes a mitogen-activated protein kinase required for spore morphogenesis that is expressed as a middle sporulation-specific gene. Here, we identify the cis-acting DNA elements that regulate SMK1 transcription and characterize the phenotypes of mutants with altered expression patterns. The SMK1 promoter contains an upstream activating sequence (UASS) that specifically interacts with the transcriptional activator Abf1p. The Abf1p-binding sites from the early HOP1 and the middle SMK1 promoters are functionally interchangeable, demonstrating that these elements do not play a direct role in their differential transcriptional timing. Timing of SMK1 expression is determined by another cis-acting DNA sequence termed MSE (for middle sporulation element). The MSE is required not only for activation of SMK1 transcription during middle sporulation but also for its repression during vegetative growth and early meiosis. In addition, the SMK1 MSE can repress vegetative expression in the context of the HOP1 promoter and convert HOP1 from an early to a middle gene. SMK1 function is not contingent on its tight transcriptional regulation as a middle sporulation-specific gene. However, promoter mutants with different quantitative defects in SMK1 transcript levels during middle sporulation show distinct sporulation phenotypes.

Calcium-Calmodulin-Dependent Protein Kinases↗