Biomedical subjects

Yan Yang

Publications and source records attributed to Yan Yang.

At least 109 records · Page 6Linked to original sources

PubMed2003

Synleurin, a novel leucine-rich repeat protein that increases the intensity of pleiotropic cytokine responses.

We have identified and characterized a novel single span transmembrane leucine-rich repeat protein, synleurin, that renders cells highly sensitive to the activation by cytokines and lipopolysaccharide (LPS). The major part of the extracellular domain consists of a leucine-rich repeats (LRR) cassette. The LRR central core has 12 analogous LRR repeating modules arranged in a seamless tandem array. The LRRs are most homologous to that of chondroadherin, insulin-like growth factor binding proteins, platelet glycoprotein V, slits, and toll-like receptors. Synleurin expression was detected at low levels in many tissues, including smooth muscle, brain, uterus, pancreas, cartilage, adipose, spleen, and testis. When synleurin is ecotopically expressed in transfected cells, the cells exhibit amplified responses to bFGF, EGF, PDGF-B, IGF-1, IGF-2, and LPS. Synleurin gene (slrn) maps to human chromosome at 5q12. The name synleurin reflects its synergistic effect on cytokine stimulation and its prominent leucine-rich repeats.

Amino Acid Sequence↗

PubMed2003

Involvement of serum response factor isoforms in myofibroblast differentiation during bleomycin-induced lung injury.

Serum response factor (SRF) is a transcription factor essential for smooth muscle (SM) myogenesis. Its role in myofibroblast differentiation is, however, unknown. We studied the expression and the localization of SRF in bleomycin-induced pulmonary fibrosis, where myofibroblasts are abundant. We found that SRF levels were upregulated in bleomycin-exposed mouse lungs mainly due to de novo synthesis of SRFDelta5, a less myogenic SRF isoform. Before myofibroblast differentiation, SRF/SRFDelta5 was immunolocalized mostly in the cytoplasm of scattered fibroblasts at lesion sites. With the development of myofibroblasts, however, SRF/SRFDelta5 was found in myofibroblast nuclei. cDNA array analysis showed that SRFDelta5 and SRF induced expression of transforming growth factor-beta1, a critical factor in myofibroblast differentiation. This was accompanied by de novo expression of several inflammatory cell-specific mRNAs. The latter was confirmed by reverse transcriptase-polymerase chain reaction. Treatment of lung fibroblasts with tumor necrosis factor-alpha, which is produced early in the bleomycin model, induced SRFDelta5 expression and SRF/SRFDelta5 cytoplasmic accumulation, whereas addition of transforming growth factor-beta1 caused SRF/SRFDelta5 nuclear translocation followed by SM alpha-actin synthesis. Interleukin-4, another cytokine involved in myofibroblast differentiation, did not affect SRF or induce SRFDelta5 expression. Our studies therefore suggested a new mechanism whereby SRF and SRFDelta5 contribute to the emergence of myofibroblasts in lung injury and fibrosis.

Animals↗

PubMed2003

Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold.

The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. Despite its clinical relevance, the potential of ECT to identify mouse epilepsy models in genetic studies has not been thoroughly assessed. We adopted the ECT test to screen the progeny of ethylnitrosourea treated male C57BL/6J mice. In a small-scale screen, several mutant lines conferring a low threshold to ECT minimal clonic seizures were mapped to the telomeric region of mouse chromosome 2 in independent founder families. This high incidence was suggestive of a single spontaneous event that pre-existed in the founders of mutagenized stock. Genetic and physical mapping led to the discovery that several lines shared a single mutation, Szt1 (seizure threshold-1), consisting of a 300 kb deletion of genomic DNA involving three known genes. Two of these genes, Kcnq2 and Chrna4, are known to be mutated in human epilepsy families. Szt1 homozygotes and heterozygotes display similar phenotypes to those found in the respective Kcnq2 knockout mutant mice, suggesting that Kcnq2 haploinsufficiency is at the root of the Szt1 seizure sensitivity. Our results provide a novel genetic model for epilepsy research and demonstrate that the approach of using ECT to study seizures in mice has the potential to lead to the identification of human epilepsy susceptibility genes.

Animals↗

PubMed2003

Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease.

Cell cycle events play a major role in the loss of neurons in advanced Alzheimer's disease (AD). It is currently unknown, however, whether the same is true for the neuronal losses in early disease stages. To explore this issue we analyzed brain autopsy material from individuals clinically categorized with mild cognitive impairment (MCI), many if not most of whom will progress to AD. Immunocytochemistry for three cell cycle-related proteins, proliferating cell nuclear antigen, cyclin D, and cyclin B, was performed on sections from hippocampus, basal nucleus of Meynert, and entorhinal cortex. The results obtained from MCI cases were compared with material from individuals diagnosed with AD and those without cognitive impairment. In both hippocampus and basal nucleus, there was a significant percentage of cell cycle immunopositive neurons in the MCI cases. These percentages were similar to those found in the AD cases but significantly higher than non-cognitively impaired controls. In entorhinal cortex, the density of cell cycle-positive neurons was greater in MCI than in AD. However, we observed large variations in the percentages of immunopositive neurons from individual to individual. These findings lend support to the hypothesis that both the mechanism of cell loss (a cell cycle-induced death) and the rate of cell loss (a slow atrophy over several months) are identical at all stages of the AD disease process. The implication of the findings for human clinical trials is discussed.

Aged↗

PubMed2003

Association of fibrin monomer polymerization function, cerebrovascular risk factors and ischemic cerebrovascular disease in old people.

In order to investigate the association of fibrin monomer polymerization function (FMPF) with traditional cerebrovascular risk factors and ischemic cerebrovascular disease in old people, 1:1 paired case-control comparative study was performed for FMPF and traditional cerebrovascular risk factors on 110 cases of old ischemic cerebrovascular disease and 110 controls matched on age, sex and living condition. The results showed that cerebrovascular risk factors were more prevalent in case group than in control group. In the case group, FMPF was significantly higher than in control group. There was a significant positive correlation between hypertension and fibrin monomer polymerization velocity (FMPV), hypertension and fibrinogen (Fbg), alcohol consumption and Fbg, but no significant correlation between diabetic mellitus, smoking and FMPF was found. Among the parameters of blood lipids, there were significant positive correlations between total cholesterol (TC) and parameters of FMPF to varying degrees, triglycerides (TG) and FMPV, TG and Fbg. Our results also showed there were significant linear trends between TC and FMPV (P < 0.001), TC and Fbg (P = 0.0087), TG and FMPV/Amax (maximum absorbance) (P = 0.0143) respectively. Multiple logistic regression analysis revealed that FMPF in case group remained significantly higher than control group after adjustment of all risk factors that were significant in univariate analysis. It was concluded that there is a possible pathophysiological link between FMPF and cerebrovascular risk factors. An elevated FMPF is associated with ischemic cerebrovascular disease and an independent risk factor of this disease. In old people, detection of FMPF might be a useful screening to identify individuals at increased cerebrothrombotic risk.

Aged↗

PubMed2003

Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex.

The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K(C4), in the ninth intron. The remainder does not. The C4 serum proteins are highly polymorphic and their concentrations vary from 100 to approximately 1000 microg/ml. There are two distinct classes of C4 protein, C4A and C4B, which have diversified to fulfill (a) the opsonization/immunoclearance purposes and (b) the well-known complement function in the killing of microbes by lysis and neutralization, respectively. Many infectious and autoimmune diseases are associated with complete or partial deficiency of C4A and/or C4B. The adverse effects of high C4 gene dosages, however, are just emerging, as the concepts of human C4 genetics are revised and accurate techniques are applied to distinguish partial deficiencies from differential expression caused by unequal C4A and C4B gene dosages and gene sizes. This review attempts to dissect the sophisticated genetics of complement C4A and C4B. The emphases are on the qualitative and quantitative diversities of C4 genotypes and phenotypes. The many allotypic variants and the processed products of human and mouse C4 proteins are described. The modular variation of C4 genes together with the serine/threonine nuclear kinase gene RP, the steroid 21-hydroxylase CYP21, and extracellular matrix protein TNX (RCCX modules) are investigated for the effects on homogenization of C4 protein polymorphisms, and on the unequal genetic crossovers that knocked out the functions of CYP21 and/or TNX. Furthermore, the influence of the endogenous retrovirus HERV-K(C4) on C4 gene expression and the dispersal of HERV-K(C4) family members in the human genome are discussed.

Animals↗

PubMed2003

Relationship between complement components C4A and C4B diversities and two TNFA promoter polymorphisms in two healthy Caucasian populations.

The RP-C4-CYP21-TNX (RCCX) modules and the tumor necrosis factor (TNF) gene cluster are probably the most polymorphic genomic regions in the human central major histocompatibility complex (MHC). Using definitive methods for genotypic and phenotypic analyses of complement components C4A and C4B, determination of the RCCX length variants, and SSP-PCR/RFLP analyses of TNFA promoter polymorphisms at positions -308 and -238, we studied the complex relationships between the C4 and TNFA polymorphisms in two normal Caucasian populations. The patterns of the RCCX modular structures and the allelic frequency of -308A TNFA (TNF2) were similar between the Budapest (n = 125) and the Ohio (n = 80) Caucasians. However, the frequency of the -238A allele was significantly higher in the Ohio (11.3%) than in the Budapest (1.6%) study population (p < 0.0001). Marked features were found in the RCCX length variants in the TNF2 carriers and noncarriers. Strong associations were found between the C4AQ0 B1 haplotype from the monomodular short (mono-S) RCCX structure and the TNF2 allele, and between the C4A6 B1 haplotype from the bimodular long-short (LS) structure of the RCCX and the TNFA -238A allele. However, 36%-46% of the TNF2 carriers did not associate with a mono-S in both study cohorts, and 57.1% of the TNFA -238A carriers in Ohio did not associate with C4A6, which has a defective complement C5 convertase activity. The carriers of TNF2 allele had significantly lower C4A serum concentration (0.17 +/- 0.08 g/l) than noncarriers (0.23 +/- 0.09 g/l) (p < 0.001). The lowest C4A serum levels were found in TNF2 carriers with mono-S structures (0.14 +/- 0.06 g/l). In essence, our results demonstrated the heterogeneities of the TNFA promoter polymorphisms, and the linkage disequilibrium of TNFA -308A and -238A alleles with complement C4A deficiency and impaired C4A protein function, respectively.

Blotting, Southern↗

PubMed2003

Tissue inhibitor of metalloproteinase-3 downregulation in lymphangioleiomyomatosis: potential consequence of abnormal serum response factor expression.

Pulmonary lymphangioleiomyomatosis (LAM) is characterized by abnormal smooth muscle-like cell proliferation leading to tissue destruction and cyst formation. We demonstrate that serum response factor (SRF), a critical smooth muscle transcription factor, is overexpressed in LAM cells. To determine whether abnormal SRF levels might have a pathogenic role in LAM, we transfected SRF into mouse lung fibroblasts and performed a cDNA array analysis. High SRF level upregulated the expression of matrix metalloproteinase (MMP)-2 and MMP-14, two MMPs previously shown to be increased in LAM. In addition, SRF down-regulated tissue inhibitor of metalloproteinase (TIMP)-3, one of their inhibitors. TIMP-3 inhibition was further confirmed by reverse transcriptase/polymerase chain reaction, immunoblotting, and immunostaining of human lung fibroblasts transfected with SRF fused to DsRed2 (a red variant of green fluorescent protein). To determine the in vivo significance of our findings, we immunostained 12 LAM cases for TIMP-3. In eight of them, TIMP-3 was ubiquitously present in normal lung parenchyma, but it was absent in LAM lesions. In the remaining cases, including two out of five normal control lungs, the antibody immunoreacted exclusively with elastin, probably due to suboptimal tissue processing. Because timp-3-null mice develop spontaneous emphysema, our findings suggest that SRF-mediated TIMP-3 inhibition might contribute to the tissue damage seen in LAM.

Animals↗

PubMed2003

Experimental study on therapeutic effect of in vivo expression of Cell I-Hep II recombinant polypeptide of fibronectin on murine H22 hepatocellular carcinoma.

AIM: To investigate the inhibitory effect of in vivo expression of expressing plasmid pCH510 of recombinant fibronectin polypeptide (CH50) on hepatocellular carcinoma and the improved therapeutic effect of pCH510 in combination with chemotherapeutic agents and Hsp70-H22 hepatocarcinoma antigen peptide on tumor. METHODS: Mice were inoculated with H22 hepatocarcinoma cells. The chemotactic effect of the expression of plasmid pCH510 on immunocytes was observed after in vivo transfection, tissue slicing and HE staining. Inhibitory effect of transfection with pCH510 on murine tumor originated from different inoculative doses was observed. The inhibitory effect of immediate transfection with pCH510 after chemotherapy on tumor was compared with that of transfection 5 days after chemotherapy. The change of function and amount of mouse peritoneal macrophages and the peripheral blood immunocytes resulted from administration of chemotherapeutic agents were detected. The peptides mixture was prepared from H22 hepatocarcinoma cells. pCH510 + Hsp70-H22 antigen peptides were injected into tumor-bearing mice with or without chemotherapy, to observe the inhibitory effects on tumor. RESULTS: At the tumor tissue site injected with pCH510, there were a great number of immunocytes which mainly were macrophages, lymphocytes and neutrophils. Transfection of plasmid pCH510 inhibited significantly the murine tumor induced by different inoculative doses. The inhibitory effect was negatively correlated with the inoculative dose. The therapeutic effect was not improved by immediate transfection with pCH510 after chemotherapy, but was significantly improved by transfection with pCH510 5 days after chemotherapy. Chemotherapeutic agent decreased the number of immunocytes and suppressed their activation in vivo. After injection of drug, the amount of immunocytes was the lowest from d 1 to d 3 and returned to normal level on the 10(th) day. Transfection with plasmid pCH510 alone could inhibit tumor induced by the inoculation with 10(4) H22 cells. The tumor originated from the inoculation with 10(5) H22 cells was inhibited by pCH510+Hsp70-H22 antigen peptides and that from the inoculation with 10(6) H22 cells was inhibited by pCH510+Hsp70-H22 antigen peptides in combination with chemotherapeutic agents. CONCLUSION: In vivo expression of pCH510 recruits immune cells, inhibits tumor growth, and enhances the efficacy of chemotherapy. But the proper timing of combining chemotherapy with pCH510 must be taken into great account. The synergism of pCH510 and Hsp70-H22 peptides can improve the efficacy, which could be further enhanced if they are used following chemotherapy. Chemotherapeutic agent + pCH510 + Hsp70-H22 peptides is a promising therapeutic approach of combination treatment of tumor.

Animals↗

PubMed2003

Anti-aging effect of astragalosides and its mechanism of action.

AIM: To study the anti-aging effect of astragalosides (AST) and its mechanism of action. METHODS: Rotating rod test and step-down type passive avoidance test were performed to determine the effects of AST on motor and memory of D-galactose (D-gal)-induced senescent mice and the middle-aged mice. The proliferative response of splenocytes induced by Con A or LPS, IL-2 production of splenocytes induced by ConA of D-gal-treated mice and the middle-aged mice were also measured. RESULTS: AST (40 mg.kg(-1).d(-1), ig, for 10 weeks) was found to ameliorate age-related alternations in both motor response and memory, enhance the deteriorated cellular immunity in D-gal-treated mice and the pre-aged (17-month-old) mice. CONCLUSION: AST has an anti-aging effect on D-gal-induced senescent mice and has the effect of delaying senility of the middle-aged mice, which was related to its improvement of brain function and immunomodulatory effects.

Aging↗

PubMed2003

[The relationship between occupational stress and cardiovascular disease risk factor].

OBJECTIVE: To explore the relationship between the occupational stress and cardiovascular disease risk factors. METHODS: The subject was 93 male freight train dispatchers, the occupational stressors, personalities, and occupational strain response were measured by using questionnaires. Blood pressure, heart rate, the concentrations of the cholesterol, triglyceride, and glycosylated hemoglobin in blood serum were also measured. RESULTS: Social support score were significantly positively related to systolic pressure (r = 0.22) and diastolic pressure (r = 0.30) (P < 0.05), while job satisfaction negatively related to them and concentration of triglyceride (r = -0.37, -0.47 and -0.28 respectively, P < 0.05, P < 0.01), and self-esteem negatively to systolic pressure (r = -0.21, P < 0.05). The differences in diastolic pressure [(78.5 +/- 13.1), (83.6 +/- 8.2), (88.1 +/- 12.3), (85.8 +/- 9.8) mm Hg, P < 0.05] among groups of social support score, body mass index (BMI) (P < 0.01) among groups of job difficulty the differences in systolic pressure [(124.9 +/- 14.4), (129.7 +/- 13.1), (118.4 +/- 16.4), (133.5 +/- 23.1) mm Hg] and diastolic pressure [(85.5 +/- 11.3), (87.0 +/- 9.8), (80.1 +/- 10.1), (88.9 +/- 12.0) mm Hg] and cholesterol level in serum [(4.96 +/- 1.18), (5.39 +/- 0.85), (5.00 +/- 1.15), (4.34 +/- 0.91) mmol/L] among groups of vulnerability to stress (P < 0.05), as well as the difference in systolic pressure and glycosylated hemoglobin level in serum among groups of competition score (P < 0.05) were all statistically significant. Stepwise regression analysis showed that job time demands and negative coping affected the change of cholesterol (R(2) > 0.05); the job relation decision latitude, social support, job difficulty, personality (self-esteem and anxiety trait) and negative coping were the predictors of smoking (R(2) > 0.05). Heart rate was related to home income and competition factor of Type A Behavior (R(2) = 0.06). CONCLUSION: The psychosocial stress aspects of work may be related to some cardiovascular risk factors.

Blood Pressure↗

PubMed2003

[Effect of occupational stress on mental health].

OBJECTIVE: To study the effect of job psychological demands and job control on mental health and their interaction. METHODS: 93 male freight train dispatchers were evaluated by using revised Job Demand-Control Scale and 7 strain scales. Stepwise regression analysis, Univariate ANOVA, Kruskal-Wallis H and Modian methods were used in statistic analysis. RESULTS: Kruskal-Wallis H and Modian methods analysis revealed the difference in mental health scores among groups of decision latitude (mean rank 55.57, 47.95, 48.42, 33.50, P < 0.05), the differences in scores of mental health (37.45, 40.01, 58.35), job satisfaction (53.18, 46.91, 32.43), daily life strains (33.00, 44.96, 56.12) and depression (36.45, 42.25, 53.61) among groups of job time demands (P < 0.05) were all statistically significant. ANOVA showed that job time demands and decision latitude had interaction effects on physical complains (R(2) = 0.24), state-anxiety (R(2) = 0.26), and daytime fatigue (R(2) = 0.28) (P < 0.05). Regression analysis revealed a significant job time demands and job decision latitude interaction effect as well as significant main effects of the some independent variables on different job strains (R(2) > 0.05). CONCLUSION: Job time demands and job decision latitude have direct and interactive effects on psychosomatic health, the more time demands, the more psychological strains, the effect of job time demands is greater than that of job decision latitude.

Humans↗

PubMed2002

Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia.

OBJECTIVE: To determine the mechanisms of improved gut mucosal acidosis associated with selective inducible nitric oxide synthase (iNOS) inhibition. DESIGN: Prospective, controlled experimental study. SETTING: Animal research laboratory. ANIMALS: Fourteen domestic pigs. INTERVENTIONS: Anesthetized and mechanically ventilated pigs received continuous i.v. endotoxin for 24 h. A selective iNOS-inhibitor (1400 W, n=8) or vehicle (control, n=6) was started at 12 h of endotoxin and infused until the end of the experiment. MEASUREMENTS AND RESULTS: Before as well as at 12 and 24 h of endotoxin, portal venous flow (ultrasound probe), intestinal oxygen (O(2)) extraction, portal venous-arterial carbon dioxide (CO(2)) content difference and ileal mucosal-arterial PCO(2) gap (fiberoptic sensor) were assessed together with video recordings of the villous microcirculation (number of perfused/unperfused villi) using orthogonal polarization spectral imaging via an ileostomy. The gut wall microvascular blood flow (units) and hemoglobin O(2) saturation ( micro Hb-O(2)) were assessed with a combined laser Doppler flow and remission spectrophotometry probe. 1400 W blunted the otherwise progressive rise in the PCO(2) gap without affecting portal venous flow, regional O(2) and CO(2) exchange or the number of unperfused villi. While endotoxin markedly aggravated the heterogeneity of the microvascular blood flow and oxygenation, 1400 W had no further effect. CONCLUSIONS: Given the uninfluenced parameters of the ileal mucosal microcirculation in our model of long-term porcine endotoxemia, selective iNOS inhibition probably improved the PCO(2) gap due to a redistribution of the microvascular perfusion within the gut wall and/or an amelioration of the cellular respiration.

Acidosis↗

PubMed2002

A highly Ca2+-sensitive pool of vesicles is regulated by protein kinase C in adrenal chromaffin cells.

We have used flash photolysis of caged Ca2+ and membrane capacitance measurements to probe exocytosis in chromaffin cells at low concentrations of intracellular Ca2+ ([Ca2+]i) (<10 microM). We observed a small pool of granules that is more sensitive to [Ca2+]i than the previously described "readily releasable pool." Upon activation of PKC, this "highly Ca2+-sensitive pool" is enhanced in size to a greater extent than the readily releasable pool but is eliminated upon expression of a C-terminal deletion mutant (Delta9) of synaptosome-associated protein of 25 kDa (SNAP-25). Thus, in chromaffin cells, PKC enhances exocytosis both by increasing the number of readily releasable vesicles and by shifting vesicles to a highly Ca2+-sensitive state, enabling exocytosis at sites relatively distant from Ca2+ channels.

Animals↗

PubMed2002

Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex.

Human populations are endowed with a sophisticated genetic diversity of complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of the major histocompatibility complex class III region. We applied definitive techniques to elucidate (a) the complement C4 polymorphisms in gene sizes, gene numbers, and protein isotypes and (b) their gene orders. Several intriguing features are unraveled, including (1) a trimodular RCCX haplotype with three long C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long (L) and one short (S) C4 genes organized in LSL configurations, (3) a quadrimodular haplotype with four C4 genes organized in a SLSL configuration, and (4) another quadrimodular structure, with four long C4 genes (LLLL), that has the human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in the Japanese population. Long-range PCR and PshAI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are C4A. In four informative families, an astonishingly complex pattern of genetic diversity for RCCX haplotypes with one, two, three and four C4 genes is demonstrated; each C4 gene may be long or short, encoding a C4A or C4B protein. Such diversity may be related to different intrinsic strengths among humans to defend against infections and susceptibilities to autoimmune diseases.

Arthritis, Juvenile↗

PubMed2002

Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins.

The complex genetics of human complement C4 with unusually frequent variations in the size and number of C4A and C4B, as well as their neighboring genes, in the major histocompatibility complex has been a hurdle for accurate epidemiological studies of diseases associated with C4. A comprehensive series of novel or improved techniques has been developed to determine the total gene number of C4 and the relative dosages of C4A and C4B in a diploid genome. These techniques include (1) definitive genomic restriction-fragment-length polymorphisms (RFLPs) based on the discrete duplication patterns of the RCCX (RP-C4-CYP21-TNX) modules and on the specific nucleotide changes for C4A and C4B isotypes; (2) module-specific PCR to give information on the total number of C4 genes by comparing the relative quantities of RP1- or TNXB-specific fragments with TNXA-RP2 fragments; (3) labeled-primer single-cycle DNA polymerization procedure of amplified C4d genomic DNA for diagnostic RFLP analysis of C4A and C4B; and (4) a highly reproducible long-range-mapping method that employs PmeI-digested genomic DNA for pulsed-field gel electrophoresis, to yield precise information on the number of long and short C4 genes in a haplotype. Applications of these vigorously tested techniques may clarify the roles that human C4A and C4B gene-dosage variations play in infectious and autoimmune diseases.

Alleles↗

PubMed2002

The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes.

The disease course of a complete C4-deficient patient in the U.S. was followed for 18 years. The patient experienced multiple episodes of infection, and he was diagnosed with systemic lupus erythematosus at age 9 years. The disease progressed to WHO class III mild lupus nephritis and to fatal CNS vasculitis at age 23 years. Immunochemical experiments showed that the patient and his sibling had complete absence of C4A and C4B proteins and were negative for the Rodgers and Chido blood group Ags. Segregation and definitive RFLP analyses demonstrated that the patient and his sibling inherited two identical haplotypes, HLA A2 B12 DR6, each of which carries a defective long C4A gene and a defective short C4B gene. PCR and DNA sequencing revealed that the mutant C4A contained a 2-bp insertion in exon 29 at the sequence for codon 1213. The identical mutation was absent in the mutant C4B. The C4B mutant gene was selectively amplified by long range PCR, and its 41 exons were completely sequenced. The C4B mutant had a novel single C nucleotide deletion at the sequence for codon 522 in exon 13, leading to frame-shift mutation and premature termination. Thus, a multiplex PCR is designed by which known mutations in C4A and C4B can be elucidated conveniently. Among the 28 individuals reported with complete C4 deficiency, 75-96% of the subjects (dependent on the inclusion criteria) were afflicted with autoimmune or immune complex disorders. Hence, complete C4 deficiency is one of the most penetrant genetic risk factors for human systemic lupus erythematosus.

Adult↗

PubMed2002

Theory of wave propagation along a waveguide filled with moving magnetized plasma.

Making use of the transformation of constitutive relations for electromagnetic waves and the transformation of the wave vector in Minkowski space, we have worked out the theory of wave propagation along a waveguide filled with moving magnetized plasma (MMPW). The dispersion equations of the wave propagation in a circular MMPW are given in this paper, along with a detailed discussion of their behaviors. Numerical calculations show that there are many interesting and important features of the wave propagation along an MMPW compared with that in a stationary magnetized plasma-filled waveguide (MPW).

Journal Article↗