Biomedical subjects

M Jiang

Publications and source records attributed to M Jiang.

At least 109 records · Page 6Linked to original sources

PubMed1999

[Clinical study on antibodies against EBV in sera of patients with rheumatoid arthritis].

OBJECTIVE: Study on the relationship between the infection of Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). METHODS: The IgA and IgG antibodies against EBV capsid antigen (IgA/VCA and IgG/VCA respectively), and anti-Z protein IgG antibodies (IgG/Z) in the sera from the patients with RA, systemic lupus erythematosus (SLE), and normal controls were detected by using indirect immunofluoresence and immunobloting techniques. RESULTS: The positive rate of IgA/VCA antibody in the serum of RA patients which was significantly higher than that in SLE patients and normal subjects. The anti IgG/Z antibodies were only found in RA patients with IgA/VCA antibody. CONCLUSIONS: The results suggested that activated EB virus may play a role in the pathogenesis of RA. It is a useful laboratory method for the clinical diagnosis of RA.

Adult↗

PubMed1998

Signaling pathways mediated by the TNF- and cytokine-receptor families target a common cis-element of the IFN regulatory factor 1 promoter.

CD40 activation of B cells is strongly influenced by the presence of cytokines. However, the molecular basis for the interplay between these distinct stimuli is not clearly delineated. IFN regulatory factor 1 (IRF-1) is a transcription factor activated by either CD40 or cytokines. We have found that these different sets of signals target a common cis-acting element in the promoter of this gene, the IRF-1 gamma-activated site (GAS). Targeting of the IRF-1 GAS is not confined to activation via CD40 but extends to other stimuli that mimic the CD40 signaling cascade, like TNF-alpha and EBV. In contrast to induction of STATs by cytokines, the IRF-1 GAS-binding complex activated by CD40, TNF-alpha, or EBV contains Rel proteins, specifically p50 and p65. In this system, simultaneous exposure to CD40L together with either IL-4 or IFN-gamma does not lead to the activation of novel Rel/STAT complexes. Given the importance of IRF-1 in a variety of biologic functions from proliferation to apoptosis, our findings support the notion that modulation of IRF-1 levels may be a critical control point in B cell activation.

B-Lymphocytes↗

PubMed1998

Spine loss and other persistent alterations of hippocampal pyramidal cell dendrites in a model of early-onset epilepsy.

To explore the anatomical substrates for network hyperexcitability in adult rats that become chronically epileptic after recurrent seizures in infancy, the dendritic and axonal arbors of biocytin-filled hippocampal pyramidal cells were reconstructed. On postnatal day 10, tetanus toxin was unilaterally injected into the hippocampus and produced brief but recurrent seizures for 1 week. Later, hippocampal slices taken from these rats exhibited synchronized network bursts in area CA3C. Both the apical and basilar dendritic arbors of CA3C pyramidal cells were markedly abnormal in these epileptic rats. There was a considerable reduction in the density of dendrite spines, although the extent of this loss could vary among dendritic segments. Spine density on terminal segments of the basilar and apical dendrites was reduced on average by 35 and 20%, respectively. In addition, the diameters of these same dendritic segments were markedly reduced. Dendritic spine loss has previously been suggested to indicate a partial deafferentation of epileptic neurons, but this interpretation is difficult to reconcile with the critical role recurrent excitatory synaptic transmission plays in the generation of synchronized network burst. In this study, axonal arbors of CA3C pyramidal cells exhibited normal branching patterns, branching complexity, and varicosity density. This suggests that if deafferentation occurs, synapses other than recurrent excitatory ones are lost. The morphological abnormalities reported here would be expected to significantly alter electrical signaling within dendrites that may contribute importantly to seizures and other behavioral sequelae of early-onset epilepsy.

Action Potentials↗

PubMed1998

Role of mu heavy chain in B cell development. I. Blocked B cell maturation but complete allelic exclusion in the absence of Ig alpha/beta.

There is good evidence for a signaling role played by Ig heavy chain in the developmental transition through the pre-B cell stage. We have previously described signal-capable or signal-incapable mutants of mu heavy chain in which a signaling defect is caused by failure to associate with the Ig alpha/beta heterodimer. To further characterize the role of Ig heavy chain-mediated signaling in vivo, as well as in B cell development and allelic exclusion, we have created transgenic mice in which the B cells express these signal-capable and signal-incapable mutant mu chains. Failure of mu to signal via Ig alpha/beta results in a block in B cell development in mice expressing the signal-incapable mu. A small number of B cells in these animals do escape the developmental block and are expressed in the spleen and the periphery as B220+ transgenic IgM+ cells. These cells respond to LPS by proliferating but show no response to T-independent-specific Ag. In contrast, B cells expressing the signal-capable B cell receptor show a strong signaling response to Ag-specific stimulus. There is no Ig alpha seen in association with signal-deficient IgM. Thus, the B cell receptor complex is not assembled, and no signal can be delivered. Despite the block in developmental signaling, allelic exclusion is complete. There is no detectable coexpression of transgenic IgM and endogenous murine IgM, nor is there rearrangement of the endogenous heavy chain genes. This suggests that differing signaling mechanisms are responsible for the developmental transition and allelic exclusion and thus allows for separate examination of these signaling mechanisms.

Alleles↗

PubMed1998

Multiple neurological abnormalities in mice deficient in the G protein Go.

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice. Mice with a disrupted alphao gene (alphao-/- mice) lived but had an average half-life of only about 7 weeks. No Goalpha was detectable in homogenates of alphao-/- mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alphao-/- cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts. Loss of alphao was not accompanied by appearance of significant amounts of active free betagamma dimers (prepulse test). At the level of the living animal, Go-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alphao-/- mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all alphao-/- mice turned only counterclockwise. These findings indicate that Go plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of Go in Ca2+ channel regulation by an unknown mechanism.

Abnormalities, Multiple↗

PubMed1998

Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry.

Ca2+ release from its internal stores as a result of activation of phospholipase C is accompanied by Ca2+ influx from the extracellular space. Ca2+ influx channels may be formed of proteins homologous to Drosophila Trp. At least six non-allelic Trp genes are present in the mouse genome. Full-length human, bovine, mouse, and rat cDNAs for Trp1, 3, 4, 6 have been cloned. Expression of these genes in various mammalian cells has provided evidence that Trp proteins form plasma membrane Ca2+-permeant channels that can be activated by an agonist that activates phospholipase C, by inositol 1,4, 5-trisphosphate, and/or store depletion. We have stably expressed human Trp3 (hTrp3) in human embryonic kidney (HEK)293 cells. Measurement of intracellular Ca2+ concentrations in Fura2-loaded cells showed that cell lines expressing hTrp3 have significantly higher basal and agonist-stimulated influxes of Ca2+, Mn2+, Ba2+, and Sr2+ than control cells. The increase in Ca2+ entry attributable to the expression of hTrp3 obtained upon store depletion by thapsigargin was much lower than that obtained by stimulation with agonists acting via a Gq-coupled receptor. Addition of agonists to thapsigargin-treated Trp3 cells resulted in a further increase in the entry of divalent cations. The increased cation entry in Trp3 cells was blocked by high concentrations of SKF 96365, verapamil, La3+, Ni2+, and Gd3+. The Trp3-mediated Ca2+ influx activated by agonists was inhibited by a phospholipase C inhibitor, U73122. We propose that expression of hTrp3 in these cells forms a non-selective cation channel that opens after the activation of phospholipase C but not after store depletion. In addition, a subpopulation of the expressed hTrp3 may form heteromultimeric channels with endogenous proteins that are sensitive to store depletion.

Animals↗

PubMed1998

Bone ingrowth to implant surfaces in an inflammatory arthritis model.

Many studies have shown enhanced bone apposition to implants coated with hydroxyapatite, but the optimum implant texture, especially in abnormal trabecular bone, is unclear. The purpose of this project was to evaluate the histological and mechanical properties of cylindrical implants with three different surface textures that were placed in the cancellous bone of the distal femur of the rabbit after the production of an inflammatory knee arthritis. The three implant surfaces included a beaded surface (Group A), a beaded surface coated with hydroxyapatite (Group B), and a smooth surface coated with hydroxyapatite (Group C). The right knees of 36 rabbits were injected with carrageenan twice a week for 2 weeks. Then bilateral implantations were performed, with 12 rabbits in each group receiving identical implants in the right and left knees. The rabbits were killed 6 weeks after surgery. Mechanical (push-out test) and histomorphometric analyses were performed to determine the quality and quantity of bone ingrowth. In Group A, there was virtually no direct contact (a 20-60-microm clearance) between the bone and the beaded surfaces. Direct contact between the bone and the implant surfaces was seen in Groups B and C. The thickness and number of trabeculae were smaller on the arthritic side than on the control side for all groups but were not different between groups for either the control or the arthritic side. Mechanical testing showed that the shear strength of the interface was weaker on the arthritic side in all groups. The results suggest that inflammatory arthritis induced by carrageenan may influence the quality of local bone (osteopenic changes) and hence compromise the bone apposition and mechanical stability of the interface between the implant and bone.

Animals↗

PubMed1998

Comparison of radiography, computed tomography and magnetic resonance imaging in the detection of sacroiliitis accompanying ankylosing spondylitis.

OBJECTIVE: To compare magnetic resonance (MR) imaging, computed tomography (CT), and radiography in the detection of sacroiliitis accompanying ankylosing spondylitis (AS). DESIGN AND SUBJECTS: Nine volunteers and 24 patients were recruited. Radiography, CT, and MR imaging were completed within a 1-week period in 24 patients with AS. In precontrast MR examination, spin-echo T1, fast spin-echo T2, and gradient echo with rephasing T2* images were obtained without fat saturation using a 0.3-T imager for all volunteers and patients. Postcontrast MR examination was performed using the same precontrast SE T1 sequence for patients with AS. RESULTS AND CONCLUSIONS: MR imaging directly showed the normal cartilage in all 16 sacroiliac joints of the 8 volunteers. In the 24 patients with AS, cartilage abnormalities were observed in 42 sacroiliac joints. More diagnoses of sacroiliitis were made using MR and CT imaging than using radiography (P < 0.001). Therefore, low-field-strength MR can be useful in detecting early sacroiliitis in patients with AS. MR imaging was able to reveal early cartilage changes and bone marrow edema, which could not be found by either CT or radiography.

Adolescent↗

PubMed1998

Stabilization of a channel's open state by a hydrophobic residue in the sixth membrane-spanning segment (S6) of rKv1.4.

We report the effects of mutating a threonine residue at position 529 (T529) in the middle of the S6 segment of rKv1.4 on the voltage-dependence and kinetics of activation and deactivation. Replacing T529 with glycine (no side chain) or with a residue that has a hydrophobic side chain (T529L, T529I, T529V, T529A, or T529F) caused a slowing of deactivation, along with a negative shift in the activation curve and a voltage-dependent slowing of activation. Numerical simulation showed that these effects could be reproduced by decreasing the rate constant for a transition from open to closed states. The degree of slowing of deactivation largely correlated with the degree of increase in 529 side-chain hydrophobicity. Specifically, the 529 mutation-induced alteration in free energy change accompanying deactivation per channel could be accounted for by the increase in free energy needed to transfer the 529 side chain of one subunit from a hydrophobic environment to an aqueous environment. We propose that in the open state, the 529 side chain faces a hydrophobic protein interior. The rate-limiting step in channel deactivation includes a conformational change in one subunit's S6 segment, moving its 529 side chain to face the aqueous lumen of the pore.

Amino Acid Sequence↗

PubMed1998

Assessment of in vitro percutaneous absorption of glycolic acid through human skin sections using a flow-through diffusion cell system.

UNLABELLED: The percutaneous absorption studies were performed using a flow-through diffusion cell system with skin specimens from 24 healthy women to assess the penetration of glycolic acid (GA). Percentages of GA, based on 14C-labelled activity, found in the skin after application of 4% GA at pH 2.0 or pH 3.8, after 24 h were as follows: stratum corneum (SC)= 2.65+/-1.80 versus 1.13+/-1.14 (P<0.05); viable skin (VS)= 13.46+/-7.44 versus 2.23+/-1.51 (P< 0.05) and effluent fraction (EF) = 12.22+/-9.03 versus 1.42+/-0.77 (P < 0.05), respectively. The applications of 4-60%, GA at their native pH resulted in an increased penetration of GA through the skin. For example, application of 20% GA, pH 1.9, resulted in the following values: SC = 2.69+/-2.26 (P > 0.05); VS = 4.88+/-4.05 (P > 0.05) and EF = 30.69+/-13.25 (P < 0.05). Duration of application also affected the extent of penetration of drug. For example, application of 20% GA, pH 1.9, for 6 h resulted in the following levels: SC = 1.16+/-0.80 (P < 0.05); VS = 4.07+/-1.78 (P > 0.05) and EF = 6.12+/-4.95 (P < 0.05). IN CONCLUSION: (i) absorption of GA in human skin are pH-, strength- and time-dependent; and (ii) the in vitro method appears to provide an appropriate model to reflect in vivo absorption of GA through human skin.

Administration, Cutaneous↗

PubMed1998

Determination of a common genetic variant of luteinizing hormone using DNA hybridization and immunoassays.

OBJECTIVE: An immunologically anomalous form of LH, due to two point mutations in codons 8 and 15 of the LH beta gene, has previously been described. LH status, i.e. the discrimination between wild-type (WT) and variant (V) LH, is usually determined by immunoassays, which can be unreliable at low serum concentrations of LH. A DNA hybridization assay was therefore developed to score the LH genotype in all subjects, independent of their serum LH concentrations. To evaluate the performance of the hybridization method, and to expand our observations of the worldwide occurrence of the V-LH, we determined its frequency in additional populations. To confirm the connection between the anomalous immunoreactivity and the V-LH beta gene, we also sequenced the LH beta subunit gene of a homozygous person. DESIGN: According to the ratio of two immunoassays, one detecting only WT-LH and the other detecting equally WT and V-LH, individuals can be classified as homozygotes for the V-LH beta allele, heterozygotes or WT. DNA samples from persons with known LH status, according to the immunoassays, were used for the development and evaluation of a new allele-specific DNA hybridization assay. This assay, and PCR and restriction fragment length polymorphism analysis, were used to determine the frequency of the V-LH beta allele in DNA samples obtained from eight populations. PATIENTS: Ambulatory adult men and women, apparently healthy and with no endocrine disorders. RESULTS: The LH genotyping by immunoassays and by the new hybridization method gave identical results with all samples analysed (n = 25). The V-LH beta subunit was observed to always have the two point mutations, and to be identical with the ones previously reported. The V-LH beta carrier frequency in the DNA samples collected from various populations varied between 0 and 53.5%. CONCLUSIONS: The immunoassay technique and the hybridization assay can be used as alternatives to determine the LH status. A great variation in carrier frequency of the V-LH beta allele is observed in different populations.

Adult↗

PubMed1998

Isolation of lipolytic substances caffeine and 1,7-dimethylxanthine from the stem and rhizome of Sinomenium actum.

We attempted to isolate lipolytic substances from the stem and rhizome of Sinomenium actum Rehder et Wilson by using high-performance liquid chromatography (HPLC). S-I and S-II were isolated from the fractions showing lipolytic activity. S-I and S-II were identified as caffeine and 1,7-dimethylxanthine, respectively, by direct comparison with authentic samples. Caffeine (S-I) dose-dependently stimulated lipolytic activity in isolated fat cells of rats, at concentrations of 500 to 1000 microM. 1,7-Dimethylxanthine (S-II) also stimulated lipolytic activity at concentrations of 500 to 1000 microM. Furthermore, we found that caffeine and 1,7-dimethylxanthine enhanced catecholamine-induced lipolysis at lower concentrations of 0.1 to 1 microM.

Animals↗

PubMed1998

Differential effects of bupivacaine on cardiac K channels: role of channel inactivation and subunit composition in drug-channel interaction.

INTRODUCTION: We examined the effects of a nonspecific ion channel blocker, bupivacaine, on K channels encoded by hERG, rKv1.4, rKv4.3, and hKvLQT1 along with hIsK. Their native counterparts in the heart are important for the function of I(Kr), I(to) and I(Ks) and, thus, play an important role in repolarization. METHODS AND RESULTS: To elucidate the mechanisms and sites of bupivacaine's actions, we correlated the voltage and time dependencies of drug effects with those of channel gating. We also studied the effects of altering the C-type (hERG) or N-type (rKv1.4) inactivation process or the subunit composition (hKvLQT1 with or without hIsK) on bupivacaine's actions. The results suggest that, except for hKvLQT1 co-expressed with hIsK, bupivacaine binding occurred at depolarized voltages coinciding with channel activation. With hKvLQT1 co-expressed with hIsK, bupivacaine bound preferentially at negative voltages when channels were in the closed state, and unbound at depolarized voltages when channels opened. The C-type inactivation of hERG enhanced, whereas the N-type inactivation of rKv1.4 hindered, bupivacaine's effects. CONCLUSION: We propose that bupivacaine's actions on these K channels can be described as a nonspecific pore blockade in the inner mouth region. However, the apparent binding affinity and voltage dependence of binding can be differentially influenced by the inactivation processes occurring at two ends of the pore (C-type inactivation at the outer end and N-type inactivation at the inner end), or by the interaction between hIsK and hKvLQT1 subunits.

Anesthetics, Local↗

PubMed1998

The abp locus of Streptococcus uberis encodes a protein homologous to polar amino acid and opine binding proteins of gram-negative bacteria.

A gene locus abp was identified immediately upstream of the CAMP factor gene cfu in Streptococcus uberis. An open reading frame capable of coding for a 277-residue protein was identified. On the basis of sequence characteristics, the abp gene product is potentially a polar amino acid and opine binding component of an ATP-binding cassette type (ABC-type) transport system similar to those of Gram-negative bacteria. This membrane protein is likely lipid modified at its amino terminus and was present in five S. uberis strains and one Streptococcus parauberis strain examined.

ATP-Binding Cassette Transporters↗

PubMed1998

Deoxygenation of sickle red blood cells stimulates KCl cotransport without affecting Na+/H+ exchange.

KCl cotransport activated by swelling of sickle red blood cells (SS RBC)is inhibited by deoxygenation. Yet recent studies found a Cl--dependent increase in sickle reticulocyte density with cyclic deoxygenation. This study sought to demonstrate cotransporter stimulation by deoxygenation of SS RBC in isotonic media with normal pH. Low-density SS RBC exhibited a Cl--dependent component of the deoxygenation-induced net K+ efflux, which was blocked by two inhibitors of KCl cotransport, [(dihydroindenyl)oxy]alkanoic acid and okadaic acid. Cl--dependent K+ efflux stimulated by deoxygenation was enhanced 2.5-fold by clamping of cellular Mg2+ at the level in oxygenated cells using ionophore A-23187. Incubating cells in high external K+ or Rb+ minimized inhibition of KCl cotransport by internal Mg2+, and under these conditions deoxygenation markedly stimulated KCl cotransport in the absence of ionophore. Activation of KCl cotransport by deoxygenation of SS RBC in isotonic media at normal pH is consistent with the generalized dephosphorylation of membrane proteins induced by deoxygenation and activation of the cotransporter by a dephosphorylation mechanism. Na+/H+ exchange activity, known to be modulated by cytosolic Ca2+ elevation and cell shrinkage, remained silent under deoxygenation conditions.

Calcimycin↗

PubMed1998

The frequency of an inactivating point mutation (566C-->T) of the human follicle-stimulating hormone receptor gene in four populations using allele-specific hybridization and time-resolved fluorometry.

We have described previously in the Finnish population an inactivating point mutation (566C-->T) in the human FSH receptor (FSHR) gene. In women, this mutation causes hypergonadotropic ovarian failure with arrest of follicular maturation and infertility, whereas in men, there is variable suppression of spermatogenesis, but no absolute infertility. To determine whether the same FSHR mutation occurs in other populations, its frequency was determined in Finland, Switzerland, Denmark, and the Chinese population of Singapore. The mutation was screened for using genomic DNA extracted from whole blood or dried blood spots. Exon 7 of the FSHR gene was first amplified using a pair of biotinylated primers. The PCR products were then immobilized on streptavidin-coated microtitration wells and hybridized using short allele-specific oligonucleotide probes labeled with europium. Time-resolved fluorometry was used for europium signal detection. To test the reliability of this method, 40 isolated DNA samples and 35 dried blood spot samples were blindly tested for the 566C-->T FSHR mutation. The analyses yielded identical results with denaturing gradient gel electrophoresis and allele-specific restriction enzyme digestion of the same samples, thus demonstrating the reliability of the tested method. Automation of this procedure allows the screening of large numbers of samples, which was subsequently carried out to investigate the frequency of the 566C-->T mutation in the study populations. A total of 4981 samples from the above-mentioned 4 countries were analyzed. The frequency of the 566C-->T mutation was 0.96% for all Finnish samples (n=1976), with a strong enrichment of the mutant allele in the northeastern part of the country. Only 1 mutation carrier was identified in the samples from Switzerland (n=1162), whereas none was found in samples from Denmark (n=1094) and the Singapore Chinese (n=540). These results suggest that the 566C-->T mutation of the FSHR gene is enriched in Finland, but is uncommon in other populations.

Alleles↗

PubMed1998

Experimental study on intramuscular injection of eukaryotic expression vector pcDNA3- IL-6 on BXSB mice.

OBJECTIVE: To study the role of IL-6 in systemic lupus erythematosis (SLE). METHODS: We constructed eukaryotic expression vector pcDNA3- IL-6 encoding for IL-6 and injected it intramuscularly into BXSB mice. 22 of the 3.5-month-old male BXSB mice were divided into two groups. One group was injected with the pcDNA3-IL-6 100 micrograms per mouse twice at the interval of 20 days. Another group was injected with plasmid pcDNA3 at the same time as control. The ANA and proteinuria were monitored every 10 days, and the IL-6 activity in serum, IgG, C3 deposition and IL-6 expression in kidney detected at the 40th day. RESULTS: IL-6 encoding plasmid had harmful effects on murine SLE with increased ANA level, proteinuria, IgG, C3 deposition and IL-6 expression in kidney, but there was no difference of serum GPT levels between the two groups. CONCLUSION: Excessive production of IL-6 could play an important pathogenic role in SLE. Blocking or reducing IL-6 secretion might be a new therapy for SLE.

Animals↗

PubMed1998

HLA-DRB1 genes in 5 rheumatic disease multi-case families.

OBJECTIVE: To detect HLA-DRB1 (DR1-10) alleles in 5 families with multi-case rheumatic diseases, and to study the possible influence of DRB1 genes in the pathogenesis of rheumatic diseases. METHODS: Sequence-Specific Primer PCR (PCR-SSP) method was used to examine HLA-DRB1 alleles. Totally 36 members of 5 families and 166 healthy people were involved in this study. The results were assessed by Chi-square test. RESULTS: The HLA-DRB1 allele frequency in the patients and their relatives was similar. No significant difference was found. But DR4 allele frequency in the patients (90.9%) and their relatives (68%) was much higher than that in normal controls (16.8%) and the difference was statistically significant (P < 0.0001). In family 4, two RA patients have different DRB1 alleles, while in family 5, two patients have the same DRB1 alleles, one developed SLE and the other developed RA. CONCLUSIONS: DR4 is closely related to rheumatoid arthritis. The nelatives of RA patients may be at greater risk to develop RA than individuals without family history. Some patients had the same DRB1 allele but developed different rheumatic diseases. This suggested that there might be some common pathways in genetic predisposing of rheumatic diseases. On the other hand, only a few patients with the same DRB1 allele developed rheumatic diseases during their life, so other factors besides DRB1 gene might also be involved in the pathogenesis of rheumatic diseases.

Adolescent↗