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Background The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin–eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. Methods We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. Results Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p p = 0.004 and p p = 0.002). This association was not seen in Asian patients. Conclusions This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

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近年经皮冠状动脉介入治疗（PCI）相关抗栓领域取得了许多关键性的进展。以TWILIGHT等研究为代表的降阶治疗探索是目前PCI术后抗血小板策略研究的主流方向之一，而在合并心房颤动PCI患者中，联合新型口服抗凝药物的双联或短程三联抗栓方案的有效和安全性已获多项新研究的印证。比伐芦定新的研究结果将更新直接PCI抗凝的循证证据。新的缺血与出血风险评估标准使抗栓降阶策略的选择更加有章可依。相信更多有益的抗栓治疗探索必将造福国内PCI患者。.

ObjectiveEndoscopic mucosal biopsies of primary gastric cancers (GCs) are used to guide diagnosis, biomarker testing and treatment. Spatial intratumoural heterogeneity (ITH) may influence biopsy-derived information. We aimed to study ITH of primary GCs and matched lymph node metastasis (LNmet).DesignGC resection samples were annotated to identify primary tumour superficial (PTsup), primary tumour deep (PTdeep) and LNmet subregions. For each subregion, we determined (1) transcriptomic profiles (NanoString ‘PanCancer Progression Panel’, 770 genes); (2) next-generation sequencing (NGS, 225 gastrointestinal cancer-related genes); (3) DNA copy number profiles by multiplex ligation-dependent probe amplification (MLPA, 16 genes); and (4) histomorphological phenotypes.ResultsNanoString profiling of 64 GCs revealed no differences between PTsup1 and PTsup2, while 43% of genes were differentially expressed between PTsup versus PTdeep and 38% in PTsup versus LNmet. Only 16% of genes were differently expressed between PTdeep and LNmet. Several genes with therapeutic potential (eg IGF1, PIK3CD and TGFB1) were overexpressed in LNmet and PTdeep compared with PTsup. NGS data revealed orthogonal support of NanoString results with 40% mutations present in PTdeep and/or LNmet, but not in PTsup. Conversely, only 6% of mutations were present in PTsup and were absent in PTdeep and LNmet. MLPA demonstrated significant ITH between subregions and progressive genomic changes from PTsup to PTdeep/LNmet.ConclusionIn GC, regional lymph node metastases are likely to originate from deeper subregions of the primary tumour. Future clinical trials of novel targeted therapies must consider assessment of deeper subregions of the primary tumour and/or metastases as several therapeutically relevant genes are only mutated, overexpressed or amplified in these regions.

The aim of this study was to investigate the expression of long non-coding RNA (lncRNA)-ATB in laryngeal carcinoma (LNCa) and its relationship with the prognosis.The expression of lncRNA-ATB was examined in laryngeal carcinoma tissue specimens, as well as in normal ones by quantitative real-time polymerase chain reaction (qRT-PCR), and the interplay between lncRNA-ATB levels and clinical indicators was analyzed. In addition, the diagnostic value of lncRNA-ATB for LNCa was assessed by receiver operating characteristic (ROC) curve analysis. The patients were followed up for 5 years and the survival analysis was conducted by Kaplan-Meier test. Finally, the Cox regression model was used to analyze the factors affecting the prognosis of patients.LncRNA-ATB expression was markedly enhanced in laryngeal carcinoma tissue samples compared to the corresponding normal ones, which was relevant to T grade and clinical stage. For the diagnosis of laryngeal carcinoma using lncRNA-ATB, the area under the ROC curve (AUC) was 0.8672, the diagnostic threshold was 3.895, and the sensitivity and specificity were 83.02% and 76.42%, respectively. In addition, the overall survival rate of patients with high expression of lncRNA-ATB was markedly lower than those in low expression group. Meanwhile, T grade, clinical stage and lncRNA-ATB are found as three independent factors influencing the prognosis of LNCa.LncRNA-ATB was highly expressed in laryngeal carcinoma tissues, which was not conducive to the prognosis of patients. Therefore, this molecular marker has potential to become a new biomarker for the diagnosis and prognosis prediction of patients with LNCa.

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer, with an unfavorable prognosis of 5-year survival rates. It is of great clinical significance to further search for more efficacious and novel targets for diagnosis and therapeutic strategies. This study aimed at clarifying the role of long non-coding RNA (lncRNA) NORAD in proliferation, invasion and migration and tumor growth of NSCLC.In this study, mRNA levels of lncRNA NORAD were examined by RT-PCR. CCK-8 assay was applied to test cell viability. Furthermore, wound healing assay and transwell assay were performed to detect the migration and invasion of A549 cells, respectively. Immunohistochemistry was applied to assess the levels of CXC chemokine receptor (CXCR) 4 and CXC chemokine ligand (CXCL) 12. Mice models of NSCLC in vivo were exploited to further examine the potential role of NORAD in tumor growth. Key proteins related to Ras homolog gene family member A (RhoA) GTPase/Rho-associated kinase (RhoA/ROCK) pathway were determined by Western blot.NORAD has elevated the levels in NSCLC tissues and cells. NORAD interference dramatically inhibited tumor growth and suppressed A549 cell proliferation, migration and invasion by downregulating CXCR4 and CXCL12 expression. RhoA/ROCK signaling pathway was activated in NSCLC.This study revealed that the downregulation of lncRNA NORAD could slow down the progression of NSCLC by regulating CXCR4 and RhoA/ROCK signaling pathway.

Satb1 regulates chromatin structure and gene expression, and is aberrantly expressed in many tumors. However, there is still no report about Satb1 functions in peripheral nerve injury until now. In this study, we explored the regulatory effect of Satb1 on Schwann cells.MTT assay, transwell assay, and flow cytometry assay were respectively used to determine Schwann cell viability, migration, and apoptosis. The mRNA and phosphorylation levels of Satb1 and SHIP1 were assessed by RT-PCR and Western blotting analysis, respectively. The correlation between Satb1 and SHIP1 was examined by ChIP assay. The expressions of PI3K/AKT pathway related factors were detected by Western blotting.In the present study, we found that knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis. Conversely, over-expression of Satb1 promoted cell viability, migration, and inhibited apoptosis. Satb1 inhibited SHIP1 expression by recruiting HDAC1. Furthermore, results showed that Satb1 activated the PI3K/AKT signaling pathway by inhibiting the expression of SHIP1. SHIP1 showed significant reversal effects on the regulatory roles of Satb1 in Schwann cells. Over-expression of Satb1 and SHIP1 inhibited cell viability, migration, and promoted apoptosis.Our study demonstrated that the Satb1 knock-out could inhibit the activation of PI3K/AKT pathway by up-regulating SHIP1, thus inhibiting cell viability and migration, and promoting Schwann cell apoptosis.

A prospective study. To evaluate the effect of the surgery to reconstruct thoracic breathing in patients with high cervical spinal cord injury (CSCI). China Rehabilitation Research Center, Beijing, China. The posterior ribs (from the fifth to the eighth) were suspended on the inferior angle of the scapula on each side using titanium cables, as well as muscles and myofascial tissue in the subscapular area. After the surgery, the patients were trained for synchronous contraction of the trapezius and diaphragm muscles, and electromyography (EMG) was performed to evaluate the synchronization. The clinical symptoms and pulmonary function were assessed within 1 week before surgery and at 2, 12 and 24 postoperative weeks. Six patients with complete high CSCI received rib suspension surgery 84±26.7 days after spinal cord injury. Before the surgery, all of the patients presented with weakened cough, retention of respiratory secretions and dyspnea, while these symptoms alleviated postoperatively. The vital capacity (VC) was enhanced to be 1680±282 ml at 2 weeks after the surgery, compared with 1085±92 ml (P=0.013). The EMG showed a synchronous muscle electrical activity between the trapezius muscles and diaphragm during deep breaths. The rib suspension surgery partially restored the thoracic breathing of the patients with high CSCI, thereby improving VC, cough and expectoration.

To observe the efficacy and safety of bivalirudin use in Chinese patients with coronary heart disease (CHD) during the peri-percutaneous coronary intervention(PCI) period.A total of 3 271 patients who underwent PCI and received periprocedural bivalirudin treatment between July 2013 and October 2015 from 88 centers of China were involved in this study. The primary outcome was 30-day net adverse clinical events (NACE a composite of major adverse cardiac or cerebral events (MACE, all-cause death, reinfarction, urgent target vessel revascularization, or stroke) or bleeding), the secondary outcome was stent thrombosis at 30 days.The mean age of enrolled patients was (65.12±12.44) years old, 27.4%(889/3 244) of them were female. Percent of stable coronary disease (SCD), non-ST segment elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) was 5.0%(162/3 248), 44.6%(1 450/3 248) and 50.4%(1 636/3 248) respectively. Radial access was performed in 89.5% (2 879/3 271) patients, and 9.7% (316/3 271) and 34.1% (1 115/3 271) patients also received ticagrelor and tirofiban medication. 69.3% (2 266/3 271) patients received post-procedural bivalirudin infusion, in which 46.3% (1 050/2 266) was treated at PCI-does, with a median duration of 2.5(1.0, 4.0) h. During the 30-day follow-up, NACE occurred in 3.45% (103/2 988) patients, the incidence of MACE, death was 2.17% (65/2 994) and 1.03% (31/3 017), respectively and bleeding events were recorded in 1.37% (41/2 996) patients. Four cases (0.13%) of stent thrombosis (3 acute stent thrombosis) were recorded.Peri-PCI Bivalirudin use is safe and related with low bleeding risk in Chinese CHD patients.

Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival. We explored whether electrolyte-reduced water (ERW) could palliate HD-evoked erythrocyte impairment and anemia. Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic HD patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or ERW treatment (n=15) during an HD course. The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after HD without any treatment. HD resulted in decreased plasma VC, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb. Antioxidants treatment significantly palliated single HD course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order VCERWVE-coated dialyzer. However, ERW had no side effects of oxalate accumulation easily induced by VC. Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients.

We have made a panel of murine anti-DP monoclonal antibodies for serological typing of HLA-DP polymorphisms; they can be used in microcytotoxicity (for 7 epitopes) and binding assays (for 8 epitopes). The antibodies detect polymorphic differences in both alpha and beta chains. As immunogens we sometimes used B-lymphoblastoid lines or purified DP molecules but mostly used mouse fibroblast transfectants expressing DP molecules. The DP beta genes were made from a cloned DPB1*0201 gene by replacing its major area of polymorphism with matching stretches of DNA amplified from other alleles; cloned DPA1*01 and DPA1*02 genes were used for transfection along with the beta chain genes. The monoclonal antibodies showed reaction patterns that correlated with the presence of particular amino-acid sequence motifs; thus none of the antibodies is allele-specific. They bind instead to epitopes which are found on a number of different HLA-DP types. We have constructed frequency tables so that the epitope (motif) data can be interpreted as the most likely genotype in each case. The basic assumption to justify this work is that HLA-DP matching or mismatching will likely influence transplant outcome, particularly in bone marrow transplantation. The present challenge is to define permissive and nonpermissive combinations of HLA-DP; it may be that matching for epitopes, rather than for full alleles, will help to resolve this issue.

The aim of this study was to test natural teeth stability under various simulated types and degrees of alveolar vertical bone loss, as well as to assess the role that the surrounding bone played for maintaining tooth stability. A three-dimensional finite element model of the human maxillary central incisor with surrounding tissue, including periodontal ligament, enamel, dentin, pulp, and alveolar bone, was established. One side and multiple vertical bone loss were simulated by means of decreasing the surrounding bone level apically from the cemento-enamel junction in 1 mm steps incrementally downward for 10 mm. Natural frequency values of the incisor model with various types and degrees of bone loss were then calculated. The results showed that, with one-sided bone resorption, the model with labial bone loss had the lowest natural frequency decreasing rates (8.2 per cent). On the other hand, in cases of multiple bone loss, vertical bone resorption at the mesial and distal sides had more negative effects on tooth stability compared to vertical bone losses on facial and lingual sides. These findings suggest that the natural frequency method may be a useful, auxiliary clinical tool for diagnosis of vertical periodontal diseases.

Among older women in East Asia, and Taiwan in particular, there is little research on quality of life and the health care they receive to address the symptoms of menopause. This study evaluated factors which influence quality of life among post middle-age women in Taiwan.This cross-sectional study recruited 1250 women between 43 and 77 years of age during the year 2002. The factors investigated were demographics, menstruation status, menopausal symptoms, osteoporosis status, and use of hormone replacement therapy (HRT). SF-36 was used to assess the health-related quality of life of these women. Correlation, multiple regression and path analysis were used to test for direct and indirect relationships among the variables.There are statistical significances between menopause symptoms and quality of life across different age groups. Path analysis shows a direct positive effect of HRT and a direct negative effect of climacteric symptoms on both physical and mental components of quality of life. Age, marital status, education and osteoporosis also have direct and indirect effects, some positive and others negative, on the components of quality of life.When developing programs to enhance health in post middle-age women, consideration should be given to symptom relief as well as quality of life.

To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1-2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan.

To investigate the associations of cytochrome p450 1A1 (CYP1A1) gene polymorphisms with susceptibility to psoriatic arthritis in Taiwan.CYP1A1 gene polymorphisms were determined in 52 patients with psoriatic arthritis and in 90 healthy controls by polymerase chain reaction/restriction fragment length polymorphism.The genotype frequency of CYP1A1 4889A/G was significantly increased in patients with psoriatic arthritis in comparison with healthy controls. The phenotype frequency of CYP1A1 4889G was also significantly increased in patients with psoriatic arthritis. The genotype frequency of CYP1A1 4887C/A was significantly higher in patients with psoriatic arthritis than in controls. The allele and phenotype frequencies of 4887A were also significantly increased in patients with psoriatic arthritis. We also found that the association of CYP1A1 4887A with psoriatic arthritis was independent of 4889G but a synergistic effect was present between CYP1A1 4887A and 4889G. The CYP1A1 4889A/G and 4887C/A polymorphisms were not associated with the manifestations and severity of psoriatic arthritis.CYP1A1 4887A and 4889G may be precipitating factors for susceptibility to psoriatic arthritis in Taiwan. An additive effect was found between CYP1A1 4887A and 4889G.

Despite frequent pleuro-pulmonary involvement, spontaneous pneumothorax is rare in patients with systemic lupus erythematosus (SLE). Here, we report a 17-year-old female patient with SLE, complicated by multiple organs involvement. She initially presented with interstitial pneumonitis and pulmonary hemorrhage, followed by spontaneous pneumothorax and CNS involvement. The patient was treated with immunosuppressive agents, including steroid and cyclophosphamide pulse therapies. Spontaneous pneumothorax happened to her once again at a different location during treatment. After aggressive therapy, the disease activity of SLE gradually diminished, and pneumothorax had not recurred during the further follow-up. Therefore, the pneumothorax may occur in SLE patients with high disease activity.

Arginase and nitric oxide synthase (NOS) compete for the same substrate, L-arginine. The reciprocal regulation of arginase and NOS in L-arginine-metabolizing pathways has recently been demonstrated. Since NOS is involved in the inflammation of human arthritides, we hypothesized that this reciprocal regulation might also occur within the inflamed synovium. The present study shows that both serum arginase activity and protein levels were significantly higher in patients with rheumatoid arthritis (RA) than in patients with systemic lupus erythematosus (SLE) or osteoarthritis (OA) or in healthy controls. Arginase protein concentrations in supernatants of monocyte cultures from RA patients were also significantly higher than in those from SLE or OA patients or healthy controls. In RA patients, there was a significant correlation between the serum concentrations of arginase protein and rheumatoid factor (r = 0.82, p0.0001). These data indicate that increased arginase production is seen in RA patients, but not in other immune-related diseases, suggesting that increased arginase production is unique to, and may play an important role in, the pathogenesis of RA disease.

Since the introduction of national health insurance on March 1st 1995 in Taiwan, another 9 items (including appendectomy) were introduced into the Taiwan/prospective payment system (T/PPS). The modified T/PPS was based on those complicated appendectomy cases with secondary diagnosis or second operation where a total fee over 37,500 New Taiwan (NT) dollars was paid by National Health Insurance Bureau (NHIB) according to the real cost. The T/PPS was implemented in October 1997 due to the continuously increasing financial burden of medical expenses on the NHIB. The purpose of this study is (1) to compare the length of stay (LOS) and total medical expense of appendectomy of fee for service (FFS) and T/PPS and (2) to compare the clinical outcome of wound healing after discharge of the two systems by telephone interview. Our study investigated 100 consecutive appendectomy cases under FFS payment system and 99 consecutive appendectomy cases under T/PPS. We retrospectively analyzed LOS, operation time, and hospital cost of different items through chart review and computer data. Our results revealed that the LOS and operation time of T/PPS were significantly shorter than those of FFS (both p0.01). The total hospital cost, fee for room service, treatment, pharmacy, examination and anesthesia in T/PPS were also significantly less than those in FFS (all p0.01, except for anesthesia p0.05). There existed positive correlation between total hospital cost and LOS, operation time, fee for room service, treatment, pharmacy, examination and anesthesia both for T/PPS and FFS. To evaluate the clinical outcome of appendectomy between T/PPS and FFS, we interviewed 73 T/PPS cases and 73 FFS cases by telephone and chart review. Our results revealed that there were no significant differences in frequencies of having painful incision, clear incision wound on the day of discharge, and removal of stitches at hospital (p all0.05). We concluded that compared to FFS, T/PPS can decrease LOS and total hospital cost of appendectomy, and T/PPS's clinical outcome of appendectomy in T/PPS showed no significant difference from that in FFS.

Mammalian spermatozoa interact with the proteins secreted by the epididymis to develop fertility. Transmembrane proteins that possess a disintegrin and metalloprotease (ADAM) domains are shown to be closely related to spermatogenesis and fertilization. Our previous study demonstrated that GP-83, a glycoprotein secreted by the epididymis, was conjugated to mature sperm. In this study, a 2.1-kilobase (kb) GP-83-expressing insert was isolated from a cDNA library of human epididymis by immunoscreening using GP-83-specific antiserum. The 5' end rapid amplification of cDNA ends (RACE) and 3'-RACE of the 2.1-kb insert elucidated two isoforms of GP-83-encoding cDNA sequences, an alpha-form of 3451 base pairs (bp) and beta-form of 2643 bp. Both forms exhibit the same open reading frame of 2262 bp predicting a peptide of 754 amino acid residues. Deduced amino acid sequence revealed signal sequence, prodomain, metalloproteinase, disintegrin, cysteine-rich, epidermal growth factor-like, transmembrane, and cytoplasmic domains. The GP-83-encoding sequence was recognized as human ADAM7 due to significant homology to other ADAM7s. According to the DNA sequences elucidated in the Human Genome Project, h-ADAM7 was located at chromosome 8p22. Ex vivo expression confirmed that h-ADAM7 cDNA did encode GP-83. Northern blot analysis revealed two transcripts of 4 kb and 3 kb in the epididymis, but not in testis or other major tissues. These results indicate that the GP-83-encoding gene is a human epididymis-associated ADAM7 gene (human ADAM7, h-ADAM7) and may be involved in the sperm-egg interaction.

To investigate the association of tumor necrosis factor (TNF) promoter polymorphisms with rheumatoid arthritis (RA) in Taiwan.TNF promoter polymorphisms at positions -238, -244, -308, -376, -857, and -863 were determined in 97 patients with RA and 97 healthy controls using the PCR-RFLP method.The phenotypic frequency of TNF-308A was significantly lower in patients with RA than in healthy controls. This finding can only be found in HLA-DR4 negative patients, not in DR4 positive RA patients and controls. The TNF promoter polymorphisms at positions -238, -244, -308, -376, -857, and -863 were not related to the clinical manifestations of RA patients.TNF-308A itself or a neighboring gene may be a protective factor for the development of RA in the HLA-DR4 negative population in Taiwan. TNF promoter polymorphisms were not associated with the clinical manifestations of patients with RA in Taiwan.

To investigate the role of HLA-DQA1 genotypes and their interaction with HLA-DRB1 in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, HLA-DQA1 was determined in 71 patients with RA and 108 healthy controls by SSP-PCR method. HLA-DRB1 and HLA-DQA1 were simultaneously detected in 55 RA patients and 101 healthy controls. PCR/SSOP method was used to determine the HLA-DRB1 genotypes, and the subtypes of HLA-DR4 were determined by cloning and sequencing. The phenotypic frequency of HLA-DQA1*0301 was significantly lower in RA than in controls, and, in contrast, the HLA-DQA1*0302 and DQA1*0303 were significantly higher in RA than in controls. The associations of DQA1*0301, *0302, and *0303 with RA were independent of DR4 and DRB1*0405. Moreover, the interactions between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303 could enhance the development of RA. We also found that the prevalence of bone erosion and seropositivity of rheumatoid factor (RF) were significantly higher in HLA-DQA1*0303 positive RA patients than in healthy controls. HLA-DQA1*0302 and DQA1*0303 are the risk factors for susceptibility to RA, while HLA-DQA1*0301 is a protective factor. A synergistic effect for the susceptibility to RA can be found between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303. We also found that the HLA-DQA1*0303 was related to bone erosion and seropositivity of RF in RA patients.

Familial Mediterranean fever is a rare disease characterized by cyclic attacks of fever, serositis and strong family background. Here we report a 22-year-old man who suffered from recurrent fever accompanied by chest and abdominal pain for more than 10 years. The attack frequency was about once per 2-3 weeks. Although he consulted many clinics and even received appendectomy at the age of 15, no definite diagnosis was given. During the admission, many laboratory examinations failed to show any abnormality except mild leukocytosis and elevated C-reaction protein. Image studies including chest X ray and abdominal CT scan showed negative result but, interestingly, Gallium-67 scan showed a hot spot in right lower chest and right lower abdomen. After prophylaxis with colchicine 1.0 mg per day, he has enjoyed more than 2 years without the above symptoms.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major agents responsible for hepatitis in Taiwan. The purpose of this study was to assess the serum alanine aminotransferase (ALT) activity in relation to HBV and HCV infection among drug abusers. This survey included 769 male drug abusers aged 14-59 years, from the Kaohsiung Narcotic Abstention Institute and Kaohsiung Prision. The prevalence of HBsAg seropositivity was 21.5%, and anti-HCV seropositivity was 27.2%, respectively. Drug abusers with HBsAg or anti-HCV had higher serum AST and ALT levels than those without HBsAg and anti-HCV. The prevalence of raised ALT and AST (or =45 IU/liter) in the HCV-positive group was more significant than in the negative group, while that of the HBsAg-positive group did not reach statistical significance. Among the HCV-positive group, ALT levels are more closely associated with HCV infection than AST levels. Our results indicated that HCV infection plays an important role in the etiology of raised ALT activity among drug abusers, while HBV infection plays a minor role. ALT screening still remains a simple and valuable method in the early recognition of HCV infection.

This study is designed to investigate the synthesis of maturation-related wheat germ agglutinin (WGA) binding glycoproteins in the human corpus epididymal epithelial cells by in vitro culture. Epithelial cells were isolated from the corpus of human epididymides and cultured with RPMI 1640 medium supplemented with 10% fetal calf serum in type IV collagen-coated dishes at 37 degrees C. The epithelial nature, presence of fibroblasts, WGA-binding sites, and existence of GP-83 were determined by an indirect immunocytochemical and histochemical staining technique. Proteins in the cultured cells were analyzed by SDS-PAGE and autoradiography. After culturing for 10 days, the cells were shown to be positive with epithelial cell-specific keratins but devoid of fibroblasts. WGA-binding granules and positive binding sites of GP-83 were also detected in the cytoplasm. Immunoblots of cell extracts probed with the anti-GP-83 antibody from seminal fluid revealed the sperm maturation-related glycoprotein GP-83. The results indicate that WGA-binding proteins may be synthesized by the corpus epididymal epithelial cells of human and GP-83 may play an important role in sperm maturation. This culture model may be suitable for the investigation on the biosynthesis and physiology of human epididymal principal cells in vitro.

The purpose of this study was to determine the correlation between the prevalence of hepatitis C virus (HCV) infection with duration of drug use and other risk factors among drug users. This survey covered 899 male drug users from Kaohsiung Narcotic Abstention Institute and Kaohsiung prison. The prevalence of positive anti-HCV was 67.2% among intravenous drug users (IVDU) and 14.7% among non-intravenous drug users (non-IVDU). Among intravenous (IV) drug users, age and duration of drug use were independently related to HCV seropositivity. Seroprevalence rate for HCV in the IVDU group increased with increasing duration of injection use within the first seven years of drug use. However, the steepest trajectory in seroprevalence of HCV infection occurred within the first four months. Due to the high rate of HCV infection among drug users, investigation of risk behaviors should be routine in such a group. A high frequency of HCV infection was also found among short-term injectors, which indicated that early risk reduction intervention was an important measure in moderating HCV infection.

OBJECTIVE. To investigate the relation of HLA-DMA and DMB alleles to the development of systemic lupus erythematosus (SLE).We studied HLA-DMA and DMB alleles in 108 patients with SLE and 138 healthy controls using the amplification created restriction site method.The phenotypic frequency of HLA-DMA*0104 was significantly higher in patients with SLE than in healthy controls. The HLA-DMA and DMB alleles were not related to clinical manifestations and various laboratory tests in patients with SLE.HLA-DMA*0104 may be associated with the susceptibility of SLE.

There is as yet no suitable routine laboratory test for a blood transfusion service to detect bacterial contamination in platelets. This study evaluates the effectiveness and the applicability of short-term bacterial culture for such a purpose.Samples from 5-unit platelet pools were inoculated into an aerobic culture bottle, then monitored for 48 h at 35 degrees C in an automated monitoring and detection system.26,210 whole-blood-derived platelet components were tested, of which 14 (0.053%) platelet units were found to be contaminated. In addition, nine of the associated red cell units and 4 fresh-frozen plasma units grew the same organisms on culture.Short-duration bacterial culture by an automated system is effective and suitable for routine screening in a regional transfusion center.

The purpose of this study was to determine the risk factors for hepatitis C virus (HCV) infection among drug abusers in southern Taiwan. This survey included 935 drug abusers from Kaohsiung Narcotic Abstention Institute and Kaohsiung prison. The prevalence of anti-HCV antibody was 29.1% among male drug abusers and 19.4% among female drug abusers. The seroprevalence of anti-HCV antibody was 66.4% among intravenous drug abusers and 14.4% among nonintravenous drug abusers. Intravenous drug use, a history of hepatitis, having tattoos, and age were independently related to HCV seropositivity among drug abusers. The prevalence of anti-HCV antibody concentrations significantly increased (10.8-fold) with intravenous drug abuse and with having tattoos (1.7-fold). These findings suggest that hepatitis C virus is mainly transmitted by the parenteral route among drug abusers in southern Taiwan. Due to the high rate of HCV infection among drug abusers, investigation of high-risk behavior should be routine in this group. To prevent HCV infection, emphasis on the use of sterile needles and aseptic procedures in tattooing is important in Taiwan.

Overproduction of interleukin-10 (IL-10) may play an important role in the development of systemic lupus erythematosus (SLE) or lupus nephritis. There is also a polymorphic dinucleotide repeat in the human IL-10 promoter region (IL-10PR). Our aim was to study whether or not the IL-10PR alleles contributed to the susceptibility to SLE or lupus nephritis. One hundred SLE patients and 103 healthy controls were studied for IL-10PR by PCR and electrophoretic analysis. The distribution of IL-10PR alleles, genotypes and the sum of both alleles (SBA) from different groups or subgroups were analyzed. SLE patients showed no difference in the distribution of IL-10PR alleles, genotypes and SBA, as compared to healthy controls. Lupus nephritis patients (N = 49) also showed no difference in IL-10PR alleles, genotypes and SBA, as compared to SLE patients without nephritis (N = 51). Of 49 lupus nephritis patients, ten developed end-stage renal disease (ESRD) and four of them were found to suffer from rapid progressive renal failure (RPRF). Patients with RPRF presented much smaller SBA than other ESRD patients (p = 0.005). Lupus nephritis patients carrying small SBA (18) suffered from a higher prevalence of RPRF than lupus nephritis patients without small SBA (50% V.S. 0%, p0.001, relative risk 82). Our data provide the first evidence of a strong association between IL-10PR and severe progression of lupus nephritis in human patients. In the future, a prospective genetic analysis of IL-10PR for patients with lupus nephritis is recommended. It might be helpful for physicians to identify the lupus nephritis subgroup with a high risk of developing RPRF early, because this might lead to a better therapy and prognosis for these patients.

To investigate the correlation of T cell receptor (TCR) genes to rheumatoid arthritis (RA) in Taiwan, synovial fluid and peripheral blood were examined simultaneously in 14 patients with RA, and peripheral blood only was examined in 15 healthy controls. RNA was extracted from T cell in synovial fluid and peripheral blood, and cDNA was synthesized using the reverse transcription method. Then, TCR-V alpha and V beta gene families were determined using the polymerase chain reaction and slot blot methods. The numbers of TCR-V alpha and V beta families, especially V beta, were decreased in rheumatoid synovial fluid compared with numbers found in the peripheral blood of the same RA patients. TCR-V beta 7 and V beta 8 could be found in the synovial fluid of all patients with positive HLA-DR4. However, there was no significant difference in the numbers of TCR-V alpha and V beta families in peripheral blood of RA patients and the peripheral blood of healthy controls. In conclusion, restricted heterogeneity of TCR-V gene, especially V beta, can be found in synovial fluid of patients with RA. TCR-V beta 7 and V beta 8 may be related to the pathogenesis of HLA-DR4 positive RA patients in Taiwan.

To investigate the relation of HLA-DMA and DMB alleles to the development of rheumatoid arthritis (RA).We studied HLA-DMA and DMB alleles in 153 patients with RA and 138 healthy controls using the amplification created restriction site method and digestion with restriction enzymes.There was no significant difference in frequencies of HLA-DMA and DMB alleles between patients with RA and controls. The HLA-DMA and DMB alleles were not related to extraarticular involvement, seropositivity for rheumatoid factor, or bone erosion. There was also no significant difference in frequencies of HLA-DMA and DMB alleles among DR4-positive and DR4-negative patients and controls.HLA-DMA and DMB do not appear to be associated with the pathogenesis of RA.

To study bone mineral density (BMD) in premenopausal adult female patients with systemic lupus erythematosus (SLE) and its relation with clinical parameters, 56 SLE patients (mean age 31 years, mean disease duration 6.3 years) and 15 normal controls were studied. BMD at the lumbar vertebrae (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA). Classification of BMD was made according to the WHO criteria in 1994. Correlation between BMD and clinical parameters was calculated. It was found BMD in the SLE patients (0.942 +/- 0.136 g/cm2) was lower than in the control group (1.055 +/- 0.080 g/cm2) (P0.01). According to the WHO criteria, 17 patients (30%) had normal BMD, 22 patients (40%) had osteopenia and 17 patients (30%) had osteoporosis. BMD was inversely correlated with disease duration in SLE patients (p0.005). The minimal disease duration for a female SLE patient to develop osteopenia was 3.5 years. In conclusion, SLE patients have lower lumbar BMD than normal controls. SLE patients with longer disease duration have lower BMD. In order to achieve early prevention of osteoporosis, we suggest that female SLE patients with disease duration for more than 3.5 years should take a BMD examination.

The purpose of this study was to investigate the prevalence of hypercholesterolemia among subjects having diabetes and glucose intolerance, according to the guidelines of the National Cholesterol Education Program (Adult Treatment Panel II, ATP II). This survey consisted of 2090 subjects (856 men, 1234 women) aged 30 years or more from the Sun-Ming district of Kaohsiung city. Glucose tolerance status was ascertained for both medical history and a 75-g oral glucose tolerance test according to World Health Organization criteria. Frequency of elevated total cholesterol in female subjects with abnormal glucose tolerance is significantly greater than in those with normal glucose tolerance (NGT). However, only male subjects with undiagnosed NIDDM (UDDM) had a statistically higher rate of hypercholesterolemia than those with NGT. Of UDDM individuals, 68% have total cholesterol level between 200 and 239 mg/dl and two or more risk factors for heart disease or evidence of coronary heart disease or total cholesterolor = 240 mg/dl or high-density lipoprotein (HDL) cholesterolor = 35 mg/dl. Such individuals should have their low-density lipoprotein (LDL) cholesterol measured. Using the ATP II, LDL cholesterol levels warranting dietary treatment for hypercholesterolemia would be expected in 76% of UDDM. Due to the high prevalence of coronary heart disease in diabetic patients, investigation of blood lipid levels and coronary heart disease risk factors should be routine in these patients, and treatment strategies should include management of lipid disorders and the many other risk factors. A high frequency of dyslipidemia was found among UDDM group in our study. Early detection of undiagnosed diabetic patients is also very important in decreasing the prevalence of coronary heart disease.

To investigate the role of HLA-DP alleles in the pathogenesis of rheumatoid arthritis (RA).HLA-DPB1 alleles were studied in 144 patients with RA and 144 healthy controls using the polymerase chain reaction/sequence specific oligonucleotide probe method.HLA-DPB1*0510 was the the most common allele in patients with RA and healthy controls in Taiwan. There was no significant difference in frequencies of HLA-DPB1 alleles between patients and controls. The HLA-DPB1 alleles were not associated with seropositivity for rheumatoid factor, extraarticular involvement, or bone erosion in patients. There was also no significant difference in frequencies of HLA-DPB1 alleles among DR4-positive and DR4-negative patients and controls.There was no significant difference in the prevalences of HLA-DPB1 alleles between Taiwanese patients with RA and healthy controls. HLA-DPB1 alleles were not related to the clinical manifestations of patients with RA in Taiwan.

We described a case of acute promyelocytic leukemia with O blood type who received bone marrow transplantation during a second remission from his HLA identical, B blood type sibling. Using PCR genotyping of the ABO group and analysis of the variable number of tandem repeats of the D1S80 locus, we could quickly document the successful early engraftment in this patient. We emphasize that the use of PCR ABO genotyping is a quick and valuable method which could be applied to assess the engraftment and its follow up in those transplant cases with donors of mismatched blood groups.