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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 235 records · Page 13Linked to original sources

The load-displacement characteristics of neonatal rat cranial sutures.

OBJECTIVE: Recently several centers have attempted to distract the craniofacial skeleton in infants with craniosynostosis. To effectively achieve this goal, we must first understand the normal sutural response to tensile forces. The objective of this study was to determine the load-displacement characteristics of neonatal rat sutures. METHODS: Thirty cranial sutures were harvested from 1-week-old Wistar rats (10 each coronal, posterior frontal, and sagittal). The width of the harvested bone-suture-bone construct was standardized to 4 mm. The specimens, kept moist, were mounted fresh and distracted at 10 microm/sec until rupture using a Vitrodyne V1000 universal tester. Standard load-displacement curves were constructed. The stiffness, defined as tensile force/change in suture length, and the ultimate stress, defined as tensile force at suture rupture/cross sectional area, were calculated. RESULTS: These sutures demonstrated classical viscoelastic behavior. During the elastic phase, they elongated approximately 1 microm for every 1 g of force (10(4) N/m). The ultimate tensile stress was approximately 4 MN/m2. The estimated mean elastic modulus was 10 megapascals. The posterior frontal sutures were significantly less stiff than the other two sutures (Kruskal-Wallis nonparametric analysis of variance, p = .0023). The difference in the ultimate stress was also significant (p = .0201). CONCLUSIONS: This study provides data regarding the basic mechanical behavior of neonatal cranial sutures in a mammalian system.

Analysis of Variance↗

Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2.

GABA (gamma-aminobutyric acid), as the main inhibitory neurotransmitter in the brain, plays an essential role for the overall balance between neuronal excitation and inhibition by acting on GABAA receptors, which are ligand-gated chloride channels. Impaired GABAergic function contributes to certain forms of epilepsy, schizophrenia, Alzheimer's Disease, and other neurological disorders. In order to identify possible genetic features and to further study biological regulation of GABAA receptor genes whose promoter elements and sequence anomalies may contribute to epileptic disorders, as an initial step, we shot-gun sequenced a BAC clone, dj082c10 (195,909-bp in size), encompassing human gamma(2) subunit of GABAA receptor (GABRG2). It is, we believe, the first genomic sequence of the GABA receptor gamma subunit family. Four contigs were assembled from 2950 reads prior to gap in an average redundancy of eight folds over the entire region. The precision of the consensus sequence was predicted to be 99.999% after closing gaps and finishing weak regions. The nine exons of GABRG2 spans an 85-kb region that had 81 SINEs comprising 22.32%, and nine L1 elements comprising 3.40%, respectively. However, the density of L1 in the regions flanking GABRG2 gene (29.45% by 45 elements) is significantly higher than that within the gene. The length of GABRG2 introns varies in the range of 1.5 kb to 38.1 kb.

Amino Acid Sequence↗

Amyloid formation in the rat: adenoviral expression of mouse serum amyloid A proteins.

Serum amyloid A (SAA) proteins are acute-phase apolipoproteins that are associated with high-density lipoprotein (HDL) particles: SAA proteins are precursors to secondary amyloid fibril proteins and under certain conditions of chronic or recurrent inflammation these proteins are deposited as amyloid fibrils. Of two isotypes found in mouse, SAA1.1 and SAA2.1, only SAA1.1 is deposited into amyloid. The CE/J mouse is unique, in that the only isoform identified is a hybrid between SAA1.1 and SAA2.1 and the mouse does not show amyloid deposition. In the rat, a deletion in the SAA1/SAA2 gene is associated with the absence of protein in the plasma and subsequently no amyloid deposition is detected. We have generated adenoviral vectors to study the expression of SAA proteins on HDL metabolism and amyloid formation. Injection of SAA viruses into rats resulted in expression of the mouse SAA proteins in the plasma with specific association of the SAA with HDL particles. The induction of SAA proteins was comparable to that seen in mice presented with the inflammatory agent, bacterial lipopolysaccharide (LPS). Adenoviral induced SAA levels were maintained for up to several weeks without a significant decrease in SAA expression. Injection of rats with the mouse SAA1.1 adenoviral vector, followed by amyloid enhancing factor (AEF) and silver nitrate resulted in the deposition of amyloid fibrils in the spleen. After 2 weeks, amyloid could be detected in other tissues, including the heart, liver, kidneys and lungs. When animals were injected with null or the SAA2.2 virus no amyloid was detected. These studies demonstrate that the inability of the rat to develop AA amyloid is due to the lack of synthesizing an amyloidogenic SAA protein. Furthermore, the expression of the adenoviral SAA protein from the liver and incorporation onto HDL particles further supports the hypothesis that AA amyloid is derived from circulating SAA protein. The ease of use of the adenoviral vectors and the rat provide an excellent model to study the function of SAA proteins.

Adenoviridae↗

Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database.

PURPOSE: We determined the impact of positive surgical margins on prostate specific antigen (PSA) recurrence and secondary treatment in patients who underwent radical prostatectomy as definitive local treatment for prostate cancer. MATERIALS AND METHODS: We reviewed the pathology reports of 1,383 patients in the CaPSURE database, a longitudinal disease registry of men with prostate cancer, who underwent radical prostatectomy as definitive local treatment. Pathological stage, Gleason score, and the number and location of any positive surgical margins were determined in each patient. PSA recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy. Secondary cancer treatment consisted of radiation or androgen deprivation after radical prostatectomy. Adjuvant and nonadjuvant secondary treatment was given within and more than 6 months after radical prostatectomy, respectively. Kaplan-Meier event rates of PSA recurrence and secondary treatment were calculated for patients with positive and negative surgical margins. We performed multivariate Cox proportional hazards analysis to adjust for clinical differences in groups. RESULTS: Patients with positive surgical margins were significantly more likely to undergo secondary adjuvant or nonadjuvant cancer treatment and have PSA recurrence than those with negative margins. After adjusting for patient age, ethnicity, PSA at diagnosis, pathological stage and Gleason score, surgical margin status was an important independent predictor of PSA recurrence and secondary treatment (p = 0.06 and 0.0011, respectively). The number of positive margins and positive margin location had little impact on the outcomes measured. CONCLUSIONS: These data indicate that surgical margin status is an independent predictor of PSA recurrence and secondary cancer treatment in patients who underwent radical prostatectomy as definitive local therapy for prostate cancer.

Adult↗

Universal inactivation of both p16 and p15 but not downstream components is an essential event in the pathogenesis of T-cell acute lymphoblastic leukemia.

p16/p15 regulate the cell cycle pathway by inhibiting the cyclin Ds-CDK4/6 mediated phosphorylation of pRb. We reported previously that in T-cell acute lymphoblastic leukemia (T-ALL), p16 and p15 were frequently (approximately 70%) inactivated at the DNA level by deletion, mutation, or hypermethylation. Therefore, we hypothesize that inactivation of the cell cycle regulatory pathway may be essential in the pathogenesis of T-ALL, and that the remaining T-ALL with a wild-type p16/p15 gene likely harbor inactivation of these genes at RNA or protein levels. Alternatively, the downstream components of the pathway including CDK4/6, cyclin Ds, and pRb may be deregulated. In 124 primary T-ALLs, we found inactivation of the p16 and p15 genes at the DNA level in 79 (64%) and 64 (52%) samples, respectively. Only 9 of the 45 samples with wild-type p16 expressed p16 protein, whereas the remaining 36 lacked p16 expression at the RNA or protein level. In the 60 samples with an intact p15 gene, only 2 expressed p15 mRNA, and the only one analyzed lacked p15 protein. Overall, the abrogation rates for p16 and p15 at DNA/RNA/protein levels were 93% (115 of 124) and 99% (123 of 124), respectively. Although no alterations were evident in cyclin Ds or CDK4/6, pRb was hyperphosphorylated in the majority of samples investigated. These findings strongly support that both p16 and p15 are specific targets in the deregulation of the cell cycle pathway in T-ALL and that the inactivation of these genes is most likely essential in the pathogenesis of this disease.

Blotting, Western↗

Truncated activin type II receptor inhibits erythroid differentiation in K562 cells.

Two receptor serine/threonine kinases (types I and II) have been identified as signaling transducing activin receptors. We studied the possibility of inhibiting activin A-dependent differentiation in K562 cells, using a dominant negative mutant of type II receptor. A vector was constructed expressing activin type II truncated receptor (ActRIIa) that lacks the cytoplasmic kinase domain. Since activin type I and II receptors form heteromeric complexes for signaling, the mutant receptors compete for binding to endogenous receptors, hence acting in a dominant negative fashion. K562 cells were stably transfected with ActRIIa, and independent clones were expanded. The truncated cDNA was integrated into the genome of the transfectants, as shown by polymerase chain reaction; and the surface expression of truncated receptors was shown by affinity cross-linking with (125)I-activin A. In wild-type K562 cells, activin A induced erythroid differentiation and cells started to express hemoglobins. In transfected cells expressing ActRIIa, the induction of erythroid differentiation was abrogated and less than 10% of cells were hemoglobin-containing cells after culture with activin A. Further transfection with wild-type type II receptors rescued the mutant phenotype of these transfectants, indicating that the effect of ActRIIa is dominant negative. In addition, phosphorylation of the cytoplasmic kinase domain of the type II receptor in vitro confirms the autophosphorylation of this portion of the receptor. Therefore, induction of erythroid differentiation in vitro is mediated through the cell surface activin receptor, and interference with this receptor signaling inhibits this process of differentiation in K562 cells.

Activin Receptors, Type II↗

Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from The CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor.

PURPOSE: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients. MATERIALS AND METHODS: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation. RESULTS: Compared with others in the database, patients on watchful waiting were more likely to be 75 years old or older (51% versus 16%, p <0.001), white (93% versus 85%, p <0.001), and have lower serum PSA (p <0.001), organ confined disease (97% versus 88%, p <0.001) and a total Gleason score of 7 or less (97% versus 88%, p <0.001). In the watchful waiting group there was a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis. Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant predictor of treatment. CONCLUSIONS: Men who elect initial watchful waiting for prostate cancer tend to be older, have lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA at diagnosis is the dominant factor for predicting secondary treatment.

Aged↗

Excitatory lung reflex may promote inspiratory muscle fatigue in the rabbit.

BACKGROUND: Inspiratory muscle fatigue is common in severe pulmonary diseases and develops when the inspiratory effort quotient, which is the mean inspiratory pressure over maximal inspiratory pressure (PI/PIMAX), exceeds a critical value. If PIMAX is unchanged, increased PI will promote muscle fatigue. PI can be expressed as (k x VT/Cdyn) x (TI/TTOT), where k is a constant, VT is tidal volume, Cdyn is dynamic lung compliance, and TI/TTOT is inspiratory duty cycle, which is inspiratory time over the period of a respiratory cycle. The excitatory lung reflex (ELR), which can be evoked by inflammatory mediators (e.g., H2O2) or hypertonic saline to cause a vagally mediated neural hyperpnea and tachypnea, may be one of the mechanisms to promote inspiratory muscle fatigue. METHODS: To investigate whether the ELR can promote inspiratory muscle fatigue I conducted experiments in anesthetized and open-chest rabbits whose lungs were made motionless. The duty cycle, amplitude of the phrenic neurogram (which is closely correlated with VT), and burst rate were examined after initiation of the ELR by injection of hypertonic saline (8.1%, 0.1 mL) into the lung parenchyma. RESULTS: The duty cycle, amplitude, and burst rate of the phrenic activity increased by 36 +/- 7, 15 +/- 3, and 40 +/- 8% (n = 9; P < 0.01), respectively. The responses were abolished by bilateral vagotomy. CONCLUSIONS: Because Cdyn and PIMAX did not change, the ELR increased the duty cycle, phrenic amplitude, and burst rate, therefore activation of this reflex may promote inspiratory muscle fatigue and may precipitate ventilatory failure.

Animals↗

Effects of the integrated TCM-WM treatment of nephrotic syndrome on growth and sexual development.

Fifty children with nephrotic syndrome were treated by using herbal drugs for nourishing yin to reduce pathogenic fire, strengthening qi and tonifying the kidney, and promoting blood circulation and removing blood stasis in combination with glucocorticoid and immunodepressant. The body height, secondary sex characters, age of the first spermatorrhea for male and of menarche for female children, bone age measured with roentgenograms on the left wrist in 50 cases of the treatment group were compared with those in 31 cases of the control group treated by glucocorticoid and immunodepressant. The results showed that the delay of growth and sexual development as side-effects of glucocorticoid and immunodepressant were markedly reduced by the integrated TCM-WM treatment.

Anti-Inflammatory Agents↗

HDL modification by secretory phospholipase A(2) promotes scavenger receptor class B type I interaction and accelerates HDL catabolism.

During inflammatory states plasma levels of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) are reduced. Secretory group IIa phospholipase A(2) (sPLA(2)) is a cytokine-induced acute-phase enzyme associated with HDL. Transgenic mice overexpressing sPLA(2) have reduced HDL levels. Studies were performed to define the mechanism for the HDL reduction in these mice. HDL isolated from sPLA(2) transgenic mice have a significantly lower phospholipid content and greater triglyceride content. In autologous clearance studies, (125)I-labeled HDL from sPLA(2) transgenic mice was catabolized significantly faster than HDL from control mice (4.24 +/- 1.16 vs. 2.84 +/- 0.1 pools per day, P < 0.008). In both sPLA(2) transgenic and control mice, the cholesteryl ester component of HDL was more rapidly catabolized than the protein component, indicating a selective uptake mechanism. In vitro studies using CHO cells transfected with scavenger receptor class B type I (SR-BI) showed that sPLA(2)-modified HDL was nearly twice as efficient as a substrate for cholesteryl ester transfer. These data were confirmed in in vivo selective uptake experiments using adenoviral vector overexpression of SR-BI. In these studies, increased hepatic selective uptake was associated with increased (125)I-labeled apolipoprotein uptake in the kidney. We conclude that during inflammation sPLA(2) hydrolysis of HDL phospholipids alters the lipid composition of the particle, allowing for more efficient SR-BI-mediated selective cholesteryl ester uptake. This enhanced SR-BI activity generates HDL remnants that are preferentially catabolized in the kidney.

Animals↗

Distribution of a common methylenetetrahydrofolate mutation in six Chinese population groups.

The distribution of the C677T polymorphism was analyzed by the PCR-RFLP technique in the Northeast Han, the Oroqen, the Ewenki, the Daur as well as in Koreans and Mongolians. The results were compared with each other. They revealed that the frequencies of the T allele are quite different (17-47%) among the tested groups and are much higher in Chinese population groups than in others.

Asian People↗

[ABO genotyping by PCR-direct sequencing method].

OBJECTIVE: To analyze the sequence difference between human A, B, and O alleles and establish the method of ABO genotyping by PCR direct sequencing. METHODS: PCR-direct sequencing technique was used to analyze two regions of cDNA from A transferase gene, 233-433 and 660-788. RESULTS: Two nucleotide substitutions at 258th and 297th were found in 233-433 region, and a nucleotide substitution at 700th was found in 660-788 region. At 258th, the nucleotide was guanine in A and B alleles, and adenine in O allele. At 297th, the nucleotide was adenine in A allele, and guanine in B allele. As this position, O allele was subdivided into two types, O(A) and O(G). At 700th, the nucleotide was guanine in A and O alleles, and adenine in B allele. Therefore, 8 genotypes, AA, AO(A), AB, BB, BO(G), O(A) O(A), O(G) O(G) and O(A) O(G), could be clearly determined by only analyzing the 233-433 region. The other two genotypes, AO(G) and BO(A), could be further distinguished by analyzing the 660-788 region. CONCLUSION: The technique of PCR-direct sequencing provides an effective and new method for ABO genotyping further.

ABO Blood-Group System↗

[Targeting studies of humanized scFv25 fusing to TNFalpha against hepatocellular carcinoma].

OBJECTIVE: To obtain humanized engineering bifunctional antibody, which has potentialities for clinical application. METHODS: Humanized anti-human hepatocellular carcinoma (HCC) single chain fragment (hscFv25) was linked with human TNF-alpha gene to form anti-HCC bifunctional antibody, then it was subcloned into prokaryotic GST fusion expression vector pGEX 4T-1 and expressed in the host E.coli. Indirect immunofluorescent staining was performed on HCC cell smearing slides in order to evaluate the activity of the purified aim protein, then MTT trial to evaluate the cytotoxicity of hscFv25-TNFalpha to SMMC-7721, finally primary tumor regression trial in nude mice bearing HCC to evaluate the targeting therapeutic value of hscFv25-TNFalpha. RESULTS: The hscFv25-TNFalpha had the similar specificity to parental antibody HAb25 for SMMC-7721 antigen. One hour predisposed MTT trial in control with parental antibody HAb25 affirmed that hscFv25-TNFalpha was cytotoxic to targeted cell SMMC-7721 with the IC(50) to be 7.1 microg/ml. The cytotoxicity can be inhibited by parental antibody HAb25. This indicated that the cytotoxicity of hscFv25-TNFalpha to targeted cell is antibody-mediated selective cytotoxicity. The tumor regression trial to the 3mm HCC xenografts in nude mice showed that hscFv25-TNFalpha had assured targeting cytotoxicity and the efficiency was nearly up to 3/3 (1/3 complete remission, 2/3 partial remission). The cytotoxicity of the hscFv25-TNFalpha was better than that of TNFalpha, whose efficiency was only 2/3 and without complete remission. CONCLUSION: hscFv25-TNFalpha is an anti-HCC bi-functional antibody which has potentialities for clinical application.

Animals↗

[The effects of hepatitis G virus infection on clinical features and liver pathologic lesions of chronic hepatitis C].

OBJECTIVE: To explore the clinical and pathological effect of hepatitis G virus infection on chronic hepatitis C. METHODS: Detecting HGV-RNA by reverse transcription-polymerase chain reaction from serum samples of 53 chronic hepatitis C through patients as diagnosed by liver biopsy. The clinical and pathologic features of the patients with positive HGV-RNA were compared with those of patients with negative HGV-RNA. RESULTS: The results showed that 15 patients (28.3%) were positive for serum HGV-RNA and there were no significant differences in clinical manifestations, biochemical indexes, HCV-RNA positive rates and the liver pathologic lesions between these HGY RNA positive and negative groups (P > 0.05). CONCLUSIONS: These data indicate that HGV coinfection does not affect the liver lesions and HCV replication of chronic hepatitis C.

Adult↗

[One-stage vagina reconstruction using free flaps].

OBJECTIVE: To investigate the feasibility of vagina reconstruction using a free flap. METHODS: The dorsal pedal flap and the posterior leg flap have been used for vagina reconstruction in 25 cases. RESULTS: All of the operations were successful. Postoperative follow-up of the patients for 6 months to 6 years showed that the reconstructed vagina was satisfactory anatomically and physiologically. The vagina wall was not only pliable but also elastic. The married patients enjoyed their sexual life. Two of them have given birth to babies. CONCLUSIONS: Vagina reconstruction with a free flap as a new method can be performed successfully. The patients are happy with the operative results, as there is no scar left around the pudendum.

Adolescent↗

[Nitrogen content variation in litters of Deyeuxia angustifolia and Carex lasiocarpa in Sanjing plain].

This paper dealt with the litter of two dominant species Deyeuxia angustifolia and Carex lasiocarpa in swamp of Sanjiang Plain, and analyzed the seasonal variation and content feature of nitrogen in litter and its roles on maintaining matter equilibrium in ecosystems. The nitrogen content in litter decreased with the increasing temperature and above-ground biomass. The weightlessness rate of litter increased with time, and the annual accumulative weightlessness rates of D. angustifolia and C. lasiocarpa were 32.2% and 27.7%, respectively. The annual accumulative nitrogen input amount of D. angustifolia community was 1478 mg.m-2, C. lasiocarpa 587 mg.m-2, while the annual accumulative nitrogen output amount in litter of D. angustifolia community was 759 mg.m-2, C. lasiocarpa 410 mg.m-2. It was suggested that the nitrogen input amount was higher than output, and that the state of nitrogen accumulation was beneficial to the stability of the ecosystems.

Biodegradation, Environmental↗

Arg485Lys polymorphism of factor V increases the risk of coronary artery disease in a Chinese population.

OBJECTIVE: To explore the relationship between genetic variation in coagulation factor V and the occurrence of coronary arterial disease (CAD). METHODS: Unrelated 86 patients with CAD and 102 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) to detect variations in the entire twenty-five exons of the factor V gene. RESULTS: Polymorphisms in exon 4 [642 G-->T (Ser156)], exon 10 [1628 G-->A (Arg485Lys)], exon 13 [4070 A-->G (His1299Arg)] and exon 16 [5380 G-->A (Val1736Met)] were documented. The study also identified a novel polymorphism in exon 2 (327 A-->G) which did not result in amino acid residue substitution. The Leiden mutation (Arg506Gln) was not detected in any of our 188 subjects. Among the 5 polymorphisms, the allele frequency of 1628 G-->A was significantly different between CAD patients and controls (0.69 vs 0.81, chi 2 = 6.908, P < 0.01). This is the first report of this finding in a Chinese population. CONCLUSION: 1628 G-->A polymorphism is associated with CAD and it may be a risk factor for CAD morbidity in the Chinese population.

Aged↗

[Study on treatment of hyperandrogenism and hyperinsulinism in polycystic ovary syndrome with Chinese herbal formula "tiangui fang"].

OBJECTIVE: To observe the efficacy of Chinese herbal formula "Tiangui Fang" (TGF) in hyperandrogenism and hyperinsulinism patients of polycystic ovarian syndrome (PCOS), and compare with western medicine metformin. METHODS: Twenty-two anti-clomiphen citrite patients were divided into two treatment groups: "Tiangui Fang" (n = 10) and metformin (n = 12) for three months. Insulin response during oral glucose tolerance test and serum level of LH, FSH, testosterone (T), estradiol (E2) and waist to hip ratio (WHR), body mass index (BMI) were measured before and after treatment. RESULTS: After treatment for three months with metformin or TGF, fasting and the integrated insulin response to the glucose load decreased. Treated by metformin 4 out of 8 patients had restoration of menstrual cyclicity and 2 of them had double phase bases body temperature (BBT). This was accompanied by lowering in serum logT/E2 but had no significant difference, the BMI, WHR and serum E2, LH:FSH ratio were not changed. Treated by TGF for three months, 6 out of 8 patients had restoration of menstrual cyclicity and double phase BBT. This was accompanied by significant lowering in serum T, logT/E2 and BMI (P < 0.05), serum LH:FSH ratio were not changed. CONCLUSION: Both metformin and TGF can reduce the high concentration of insulin in PCOS patients and induce ovulation, the herbal formula has a better efficacy.

Adolescent↗