Search

BackgroundLupus low disease activity state (LLDAS) attainment has been reported to be associated with reduced damage accrual, flare, and mortality, as well as improved quality of life, in cohorts of SLE patients with established disease. Whether these associations are present in recent-onset disease is less well known.ObjectivesTo evaluate the associations of LLDAS attainment with outcomes in patients with recent onset SLE.MethodsData from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected prospectively between 2013 and 2020 using standard templates. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golder et al., 2019 [1]. An inception cohort was defined based on duration since SLE diagnosisResultsThe study cohort included 4,106 patients of whom 680 (16%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the non-inception cohort, inception cohort patients were significantly younger, had higher disease activity (SLEDAI-2K and physician global assessment), used more glucocorticoids and immunosuppressants but had less organ damage at enrolment and only 88 (13.6%) patients accrued damage during a median 2.2 years follow-up (Table 1).Table 1.Non-inception cohortInception cohortp-valuen=3426n=680Age at enrolment (years), median [IQR]40 [31, 51]33 [25, 44]Age at diagnosis (years), median [IQR]28 [21, 38]33 [25, 43]SLE duration at enrolment (years), median [IQR]10 [5, 16]1 [0, 1]Study duration (years), median [IQR]2.5 [1.0, 5.4]2.2 [0.9, 3.7]Females, n (%)3155 (92.1%)623 (91.6%)0.68Asian ethnicity, n (%)3037 (89.1%)595 (88.1%)0.49Prednisolone (PNL) use - ever, n (%)2865 (83.6%)620 (91.2%)Time adjusted mean (TAM)-PNL, median [IQR]5.0 [2.2, 8.6]6.2 [3.2, 10.3]Cumulative PNL (g), median [IQR]3.4 [0.5, 9.7]3.8 [1.1, 8.5]0.26Anti-Malarial use - ever, n (%)2669 (77.9%)569 (83.7%)Immunosupressant use -ever, n (%)2367 (69.1%)521 (76.6%)AMS (TAM-SLEDAI-2K), median [IQR]2.8 [1.2, 4.6]3.1 [1.6, 5.0]0.002TAM-PGA, median [IQR]0.4 [0.2, 0.7]0.4 [0.3, 0.8]Mild/moderate/severe flare ever, n (%)1789 (52.2%)391 (57.5%)0.012Organ damage accrual, n (%)629 (20.8%)88 (13.6%)LLDAS at baseline, n (%)1730 (50.5%)195 (28.7%)LLDAS-ever (at least once), n (%)2637 (78.2%)492 (73.9%)0.014≥50% time in LLDAS (LLDAS-5), n (%)1612 (50.6%)256 (41.1%)Significantly fewer inception cohort patients were in LLDAS at enrolment than the non-inception cohort (29% vs. 51%, pConclusionLLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed, due to low rates of damage accrual in the first years after SLE diagnosis.References[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.AcknowledgementsWe thank all patients participating in the Asia Pacific Lupus Collaboration (APLC) cohort, and all data collectors for their ongoing support for APLC research activities.The APLC has received unrestricted project grants from AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, and UCB to support data collection contributing to this work.Disclosure of InterestsVera Golder: None declared, Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra and Zeneca, Sanofi, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Yes. Clinical trials and/or research grants from Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche,Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca,Astellas, Gilead, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson, Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Yes. Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., Masayoshi Harigai Speakers bureau: MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: MH is a consultant for AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: MH has received research grants from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, BMDB Basnayake: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Advisory Board member for Pfizer, Eli-Lilly, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K, Sang-Cheol Bae: None declared, Sean O’Neill Paid instructor for: Advisory board member for GSK, Fiona Goldblatt: None declared, Shereen Oon: None declared, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis – co-chair for NSW and steering committee member for ARISE meeting Feb 2021Janssen Pharmaceuticals – advisory board, Grant/research support from: Novartis, Employee of: Eli Lilly, Kristine Ng Speakers bureau: speaker fees and advisory board (Abbvie, Novartis, Janssen), Annie Law: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, C.S. Lau Shareholder of: Pfizer, Sanofi and Janssen, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Consultant of: AH is on the advisory board for Abbvie and GSK, Grant/research support from: AH has received research support from AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen

Objective To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Methods This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate 3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Results Patients ( N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p Conclusion Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

AA2219-T87 alloy was self-reacting friction stir welded at different traverse speeds. Joints produced at low traverse speed exhibit tunnel defects. The tunnel defects can be avoided by higher trave...

We show how buy-and-hold investors can move from horizon uncertainty to profit opportunity. The analysis is conducted under a risk-averse framework rather than the standard Markowitz formulation in the case of i.i.d. asset processes. We make this practical achievement by considering a threshold stopping rule as the strategy to determine when to exit the market. The resulting investment horizon is random and can be correlated with the market. Under this setting, we first provide an analytical approximation to optimal weights, and then identify a class of reference variables associated with the stopping rule that leads to ex-ante improvements in portfolio allocation, vis-a-vis the fixed exit time alternative. The latter conclusion is based on a generalization of the Sharpe ratio, adjusted for horizon uncertainty. The obtained investment suggestion is simple and can be implemented empirically.

Supplemental material, LUP887799 Supplementary material for Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus by R Kandane-Rathnayake, J R Kent, W Louthrenoo, S -F Luo, Y -JJ Wu, A Lateef, V Golder, S Sockalingam, S a Navarra, L Zamora, L Hamijoyo, Y Katsumata, M Harigai, M Chan, S O’Neill, F Goldblatt, C S Lau, A Hoi, M Nikpour and E Morand in Lupus

Background Total joint replacement (TJR) is a major surgical procedure aiming to replace damaged natural joints with artificial prosthesis to restore function and alleviate pain. Total knee replacement (TKR) and total hip replacement (THR) are two common replacement procedures, mainly as a result of osteoarthritis, rheumatoid arthritis, trauma, fracture and infection. Whether gout associates with a greater risk of TJR independent of these primary risk factors is controversial, despite tophaceous or chronic deforming gouty arthritis may lead to joint destruction and subsequent TJR Objectives We carried out a case control study using the National Health Insurance (NHI) database with full coverage of the general population of Taiwan to investigate the burden of TJR in gout patients at diagnosis compared to matched controls. We further followed incident gout patients and their matched controls after diagnosis to compare their subsequent risk for TJR. Methods The Taiwan National Health Insurance database was used to identify 74,729 new diagnosis gout patients in 2005. These were matched 1:1 to 74,729 controls by birth year and sex with people who did not have gout diagnosis or urate-lowering treatment prescription. Odds ratios (ORs) of total hip or knee replacement (THR or TJR) at diagnosis and hazards ratios (HRs) after diagnosis were estimated adjusted for gender, age at diagnosis, comorbidities, co-medications, place of residence, income and occupation. Results Gout was associated with adjusted ORs (95% CIs) of 0.87 (0.54 to 1.40), 1.01 (0.57 to 1.79), 0.93 (0.64 to 1.35) for the THR, TKR and TJR at diagnosis, respectively. The incidence rate of THR or TKR in the patients with gout was 1.60 and 1.76 (per 1,000 person-years) which was higher than matched controls (0.99 and 0.98, respectively). Gout was also associated with an adjusted HR (95% CI) of 1.41 (1.19 to 1.68), 1.37 (1.16 to 1.61) and 1.37 (1.22 to 1.56) for developing THR, TKR and TJR. Conclusions Compared to matched controls people with gout did not have an increased risk of TJR at diagnosis but the risk increased substantially after diagnosis. Whether adequate urate-lowering treatment reduces the risk requires further study. References Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nature reviews. Rheumatology 2015;11:649–62. Roddy E, Zhang W, Doherty M. Are joints affected by gout also affected by osteoarthritis? Ann Rheum Dis 2007;66:1374–7. Disclosure of Interest None declared

Background There is emerging evidence suggesting that offspring born to patients with rheumatic diseases has higher risk of neuropsychiatric diseases. Previous data from Quebec showed children born to women with SLE have an increased risk of autism spectrum disorder (ASD) but data regarding risk of ASD in offspring of mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) mothers have not been reported in other population. Objectives We aimed to examine whether offspring of mothers with SLE and RA in Taiwan has a higher risk of developing ASD using data from a linkage between National Health Insurance (NHI) database and National Birth Registry in Taiwan. Methods We established a birth cohort of all live-births between 2001 and 2012 in Taiwan established using the National Health Insurance database and the National Birth Registry. Children born to mothers with SLE or RA were identified and matched up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of child, gestational age, birth weight, socioeconomic status (place of residence, income level, occupation). A marginal Cox proportional hazard models were used to estimate the relative risk (RR; 95% confidence interval [CI]) for ASD in newborns with affected mothers. Results Of 1,893,244 newborns, 0.08% (n=1,594) were born to mothers with SLE (mean age 30.43±4.37 years old) and 0.04% (n=673) were born to mothers with RA (31.97±4.51 years old). Overall, 5 of 673 (0.74%) RA offspring developed ASD, 7 of 1594 (0.44%) SLE offspring developed ASD and 10,631 of 1,893,244 (0.56%) all infants developed ASD. The incidence of ASD was 140.39 (95% CI, 45.58–327.62) per 100,000 person-years for RA group, 76.19 (95% CI, 30.63–156.97) per 100,000 person-years for SLE group, 89.85 (95% CI, 88.15–91.57) per 100,000 person-years for non-RA group and 89.87 (95% CI, 88.17–91.60) per 100,000 person-years for non-SLE group. The children born to RA and SLE mothers did not have higher risk of ASD with a HR (95% CI) of 1.42 (0.60–3.40) and 0.76 (0.36–1.59) for ASD, respectively. Conclusions Children born to women with SLE and RA do not have higher risk of developing ASD. References Lahita, R.G., Systemic lupus erythematosus: learning disability in the male offspring of female patients and relationship to laterality. Psychoneuroendocrinology, 1988. 13(5): p. 385–96. Vinet, E., et al., Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population-Based Cohort. Arthritis Rheumatol, 2015. 67(12): p. 3201–8. Disclosure of Interest None declared

Titanium dioxide nanostructures have been synthesised by annealing the Pd loaded titanium foil at 680°C under the atmosphere of Ar or Ar–H2 gas mixture. The microstructure and production of titanium dioxide are found to depend critically on the concentration of Pd catalyst and the Ar–H2 atmosphere. The catalyst of Pd and the introduction of 5%H2 gas are the key factor for the formation of the long (about 100 μm in the average) and smooth titanium dioxide nanowires at low temperature. Scanning electron microscope and X-ray diffraction show that they are all rutile phase. The further result shows that the titanium dioxide nanowires possess good crystallinity and high surface photovoltage response.

Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.

Summary Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE). Several genome-wide scan studies have suggested chromosome 1q as a genetic susceptibility locus for SLE. This study investigated the association of apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10 and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic polymorphisms with SLE susceptibility and clinical characteristics in Taiwan. This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL-10, located on 1q31–32, emerged as a significant susceptibility gene locus in Taiwanese SLE (T4 statistic = 0·01). IL-10 CA21 allele was the most common allele of 15 identified in Taiwanese, displaying skewed distribution of susceptibility in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a negative significant association with ascites and IL-10 CA25 allele increased the occurrence of the anti-cardiolipin IgM antibody. This study identified five alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in Taiwanese patients. FasL and PARP alleles displayed no skewing distribution between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17 allele demonstrated a high discoid rash presentation (T4 statistic 0·01 and 0·03, respectively) and PARP CA12 allele displayed a significant association with anti-cardiolipin IgM antibody production (T4 statistic 0·02). IL-10, FasL and PARP microsatellite polymorphisms exhibited significant associations with SLE susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23–42 is an important genetic locus for further SLE subphenotype susceptibility study.

Systemic lupus erythematosus (SLE) in the elderly is uncommon and rarely reported with disease onset at age 65 and older. The aim of this study is to retrospectively analyze the influence of age at disease onset on the clinical features and prognosis of SLE. From 1988 to 1998, we encountered 21 lupus patients with disease onset at age 65 and older (all are included in group A). For comparison, 21 lupus patients with disease onset between 50 ± 64 years of age (group B)and 152 lupus patients with disease onset before 50 years of age (group C) were obtained by a simple random sampling method from the hospital registry. Clinical features as included in the 1982 ARA revised criteria for classification of SLE and survival rate were analyzed and compared among these three groups. Group A had a smaller female to male ratio, longer duration from disease onset to diagnosis, less malar rash, more discoid lupus, and shorter survival rate that group C. There was no statistically significant difference in clinical features and survival between groups A and B, as well as between female and male patients of these two groups. The main cause of death in group A was septic shock. In conclusion, the clinical features and prognosis of SLE were influenced by the age at disease onset. However, clinical features and prognosis of SLE were similar in both late-onset lupus groups.

Nationwide data on the epidemiology of dermatomyositis (DM) and polymyositis (PM) were limited.This study was to estimate the incidence, occurrence of cancer and mortality of DM and PM in Taiwan.Both the register of critical illness of the Taiwan National Health Insurance Research Dataset and the National Death Registry of Taiwan were used to calculate estimates of the incidence, cancer association, and mortality of DM and PM between 2003 and 2007.A total of 803 DM and 500 PM cases were identified between 2003 and 2007. Mean age at diagnosis was 44·0 ± 18·3 years for DM and 49·2 ± 15·9 years for PM. The overall annual incidences of DM and PM were 7·1 (95% CI 6·6-7·6) and 4·4 (95% CI 4·0-4·8) cases per million population. The incidence of both DM and PM increased with age and reached a peak at age 50-59 years. One hundred and eleven (13·8%) patients with DM and 31 (6·2%) patients with PM had cancers. The diagnosis of most cancers was made after the diagnoses of DM (n = 71; 64·0%) and PM (n = 21; 67·7%). Overall, the standardized incidence ratios (SIR) for cancer were 5·36 (4·12-6·87) and 1·80 (1·10-2·79) among patients with DM and PM; however, during the first year, SIRs for cancer were 24·55 (95% CI 18·62-31·79) and 9·17 (95% CI 14·82-15·93) in patients with DM and PM, respectively. The most common types of cancer were nasopharyngeal cancer for men and breast cancer for women. Patients with DM and PM had standardized mortality ratios of 7·68 (6·41-9·01) and 5·29 (4·28-6·48).This study reports robust estimates of important aspects of the epidemiology of both DM and PM in Taiwan. This highlights the rarity of these diseases, and their associated cancer risks and increased mortality.

Many cancers are chemotherapy-resistant. Chemotherapy combined with immunotherapy offers a potential avenue for the treatment of chemotherapy-resistant cancers. In this study, we investigated the apoptotic pathways induced by combined interferon-gamma/adriamycin treatment in Hep G2 cells. Our data showed that Hep G2 cells treated with combined interferon-gamma/adriamycin enhanced cell apoptosis in comparison with that of cells treated with adriamycin. Interferon-y increased TNFR-1, CSE1L/CAS (cellular apoptosis susceptibility protein), Bax, and Bad levels. Adriamycin increased p53 and Bax, but not TNFR- 1 and CAS levels. Interferon-y did not increase p53 accumulation; nevertheless it enhanced adriamycin-induced p53 accumulation. Overexpression of IRF-1 augmented the combined interferon-gamma/adriamycin-induced p53 accumulation. Interferon-gamma co-treatment increased the stability of p53 protein induced by adriamycin. Our data suggest that TNF-gamma may greatly enhance the combined interferon-gamma/chemotherapeutic drug-induced apoptosis of cancers. Our findings also indicate that CAS, TN-FR-1, p53, Bax, and Bad may be the targets for the interferon-y-based chemo-immunotherapy of the chemotherapy-resistant cancers.

Aim of the study was to explore the influence of hypoxia on multidrug resistance related genes and the potential role of hypoxia-inducible factor-1-alpha (HIF-1alpha) in formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. HepG2 cells were subjected to hypoxia in a cohort of exposed time. A cell model stably expressing HIF-1alpha was established by liposome-mediated transfection of plasmid pcDNA3/HIF-1alpha into HepG2 cells. Apoptosis of HepG2 cells exposed to hypoxia or transfected by plasmid pcDNA3/HIF-1alpha was detected by Flow Cytometry after administration of chemotherapeutic drug (5-Fu). Real-time fluorescent quantitative PCR and Western-blot technique were used to analyze the expressions of multidrug resistance related genes mdr1, MRP1 and LRP at mRNA and protein level, respectively. Apoptosis Index of HepG2 cells exposed to hypoxia stepped down as exposed time extended after administration of 5-Fu. The expression of mdr1, MRP1 and LRP gene and protein revealed a hypoxic time-dependent induction and was synchronous with the alterations of HIF-1alpha in HepG2 cells exposed to hypoxia. The expressions of these multidrug resistance related genes were remarkably increased in HIF-1alpha transfected HepG2 cells as compared to empty vector transfected cells. Apoptosis index of HIF-1alpha transfected cells was obviously less than that of control cells when they were simultaneously exposed to 5-Fu for 24hrs. In conclusion, ambient hypoxia might be one of the causes for the formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. Hypoxia-elicited multidrug resistance related protein expression might be a pathway for resistance of HepG2 cells to chemotherapeutics and HIF-1alpha might be involved in this process.

Analysis of synovial fluid is important in the evaluation and treatment of arthritic conditions. This study measured the acoustic velocity of synovial fluids in patients with degenerative joint diseases, crystal arthropathy, and other inflammatory arthropathies using the ultrasonic pulse-echo method. The measured acoustic velocities of these bio-fluids were then correlated with clinical parameters including the synovial white blood cell count (WBC), clarity, viscosity, string test, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). Results showed that the acoustic velocities were correlated with ESR (p = 0.0016) and CRP (p = 0.0001). The mean acoustic velocity of inflammatory synovial fluids, defined as synovial fluids with WBCs of more than 2000/mm3, was greater than that of synovial fluids with WBCs of less than 2000/mm3 (1550 +/- 4.5 m/s vs 1544 +/- 1.5 m/s, p = 0.007). This study demonstrated that the acoustic velocity of synovial fluid correlates well with severity of inflammation. These findings suggest that measurement of acoustic velocity may be useful in the clinical evaluation and management of arthritic conditions.

Though proximal muscle weakness is characteristic of polymyositis, other agents may also lead to proximal muscle weakness, such as drugs, endocrine diseases, or infections. Here, we report a thirty year-old female suffering from proximal weakness which initially was thought to be a case of polymyositis with high serum creatine phosphokinase level. Very low thyroid hormone levels were found as the history inquiry revealed constipation, hoarseness and cold intolerance. The muscle biopsy showed no obvious inflammation. After thyroxine therapy, her muscle weakness recovered. Up to now, hypothyroid myopathy with muscle mitochondrial abnormalities shown by electron microscopic examination has not been reported in the medical literature in Taiwan. Hypothyroid myopathy, though it is rare, may be misdiagnosed as polymyositis clinically. Therefore, it is recommended that hypothyroid myopathy should be considered in the differential diagnosis of proximal muscle weakness.

Elevated levels of several cytokines including interleukin-1beta (IL-1beta) have been detected in airway fluid of asthmatic patients. Inhalation of IL-1beta induced a bronchial hyper-reactivity to contractile agonists. However, the implication of IL-1beta in the pathogenesis of bronchial hyper-reactivity is not completely understood. Therefore, we investigated the effect of IL-1beta on bradykinin (BK)-induced inositol phosphate [Ins(X)P] accumulation and Ca2+ mobilization, and up-regulation of BK receptor density in canine cultured tracheal smooth-muscle cells (TSMCs). Treatment of TSMCs with IL-1beta potentiated BK-induced Ins(X)P accumulation and Ca2+ mobilization. However, there was no effect on the Ins(X)P response induced by endothelin-1, 5-hydroxytryptamine or carbachol. Treatment with platelet-derived growth factor B-chain homodimer (PDGF-BB) also enhanced the BK-induced Ins(X)P response. These enhancements by IL-1beta and PDGF-BB might be due to an up-regulation of BK B(2) receptor density (B(max)), since [(3)H]BK binding to TSMCs was inhibited by the B(2)-selective agonist and antagonist, BK and Hoe 140, but not by B(1)-selective reagents. The enhancing effects of IL-1beta and PDGF-BB on Ins(X)P accumulation, Ca2+ mobilization and B(max) were attenuated by PD98059 [an inhibitor of activation of mitogen-activated protein kinase (MAPK) kinase, MEK] and cycloheximide (an inhibitor of protein synthesis), suggesting that IL-1beta may share a common signalling pathway with PDGF-BB via protein synthesis. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed the up-regulation of BK receptors induced by IL-1beta, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by IL-1beta might be, at least in part, mediated through activation of the Ras/Raf/MEK/MAPK pathway in TSMCs.

Bacterial lipopolysaccharide (LPS) was found to induce inflammatory responses and to enhance bronchial hyperreactivity to several contractile agonists. However, the implication of LPS in the pathogenesis of bronchial hyperreactivity was not completely understood. Therefore, in this study, we investigated the effect of LPS on mitogen-activated protein kinase (MAPK) activation associated with potentiation of bradykinin (BK)-induced inositol phosphates (IPs) accumulation and Ca(2+) mobilization in canine cultured tracheal smooth muscle cells (TSMCs). LPS stimulated phosphorylation of p42/p44 MAPK in a time- and concentration-dependent manner using a Western blot analysis against a specific phosphorylated form of MAPK antibody. Maximal stimulation of the p42 and p44 MAPK isoforms occurred after 7 min-incubation and the maximal effect was achieved with 100 microg ml(-1) LPS. Pretreatment of TSMCs with LPS potentiated BK-induced IPs accumulation and Ca(2+) mobilization. However, there was no effect on the IPs response induced by endothelin-1, 5-hydroxytryptamine, and carbachol. In addition, pretreatment with PDGF-BB enhanced BK-induced IPs response. These enhancements by LPS and PDGF-BB might be due to an increase in BK B(2) receptor density (B(max)) in TSMCs, characterized by competitive inhibition of [(3)H]-BK binding using B(1) and B(2) receptor-selective reagents. The enhancing effects of LPS and PDGF-BB were attenuated by PD98059, an inhibitor of MAPK kinase (MEK), suggesting that the effect of LPS may share a common signalling pathway with PDGF-BB in TSMCs. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by LPS and PDGF-BB, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by LPS might be, at least in part, mediated through activation of Ras/Raf/MEK/MAPK pathway in TSMCs.

1. Extracellular purine and pyrimidine nucleotides have been implicated in the regulation of several cellular functions including mitogenesis. In this study, experiments were conducted to characterize the P2Y receptor on C(6) glioma cells responsible for stimulating cell proliferation associated with mitogen-activated protein kinase (MAPK) activation. 2. UTP and ATP produced a similar effect on [(3)H]-thymidine incorporation in a time- and concentration-dependent manner, suggesting the involvement of P2Y(2) receptor in mediating proliferation of C(6) glioma cells. 3. In response to UTP, both p42 and p44 MAPK were activated in a time- and concentration-dependent manner using Western blot analysis with an anti-phospho-p42/p44 MAPK antibody. The phosphorylation reached maximal levels after 5 min and declining by 30 min. 4. Pretreatment with pertussis toxin (PTX) did not change these responses to UTP. Both DNA synthesis and phosphorylation of MAPK in response to UTP were attenuated by tyrosine kinase inhibitors, genistein and herbimycin A, protein kinase C (PKC) inhibitors, staurosporine and GF109203X, and removal of Ca(2+) by addition of BAPTA/AM plus EGTA. 5. UTP-induced [(3)H]-thymidine incorporation and p42/p44 MAPK phosphorylation was completely inhibited by PD98059 (an inhibitor of MEK1/2). Furthermore, we showed that overexpression of dominant negative mutants of Ras (RasN17) and Raf (Raf-301) completely suppressed MEK1/2 and p42/p44 MAPK activation induced by ATP and UTP. 6. These results conclude that the mitogenic effect of UTP mediated through a P2Y(2) receptor that involves the activation of Ras/Raf/MEK/MAPK pathway. UTP-mediated MAPK activation was modulated by Ca(2+), PKC, and tyrosine kinase associated with cell proliferation in cultured C(6) glioma cells.

The term chondrocalcinosis is often used to describe the radiological or pathological features of calcified joint cartilage, and it usually indicates the deposition in cartilage of calcium pyrophosphate dihydrate. The prevalence of chondrocalcinosis increases with age, with dramatic increases occurring in the decades past age 60. In younger patients with chondrocalcinosis, either clinical evidence of associated metabolic diseases leading to the chondrocalcinosis or familial disease occurrence usually can be detected. We report a 42-year-old Chinese woman with ankylosing spondylitis and arthritis involving multiple peripheral joints. Severe chondrocalcinosis was detected incidentally in this patient, however, subsequent studies revealed no associated metabolic disease or familial susceptibility and the clinical features of this patient were different from those of ankylosing chondrocalcinosis (pseudoankylosing spondylitis). The cause of chondrocalcinosis in this patient remains unknown, but joint damage and repair could have been initiating or aggravating factors of the chondrocalcinosis.

Suppurative coxitis induced by salmonella is rarely reported in the literature. Furthermore, reconstruction with a total hip arthroplasty (THA) in such patients has never been reported. However, in this study, we present 4 cases; 2 normal male patients and 2 female patients with underlying systemic lupus erythematosus (SLE). The ages range from 26 to 61 years. All 4 cases revealed growth of group B salmonella from the cultures of synovial fluid. They all received THA after the infections were eradicated. The functional assessment of pain, range of motion, walking ability together with the radiographic assessment were used according to the new hip score system. After a minimum follow-up of 2 years, all of the reconstructed hips showed good to excellent results since no infections recurred during this period. Although the long-term results are uncertain, the short-term clinical advantage of THA in the treatment of quiescent salmonella coxitis is encouraging.

Acute myocardial infarction is an important and sometimes fatal complication of systemic lupus erythematosus (SLE). We describe a case of acute myocardial infarction in a 23-year-old woman with SLE. Angiography revealed coronary ectasia in the left main and proximal circumflex coronary arteries, as well as a stenotic lesion in the left anterior descending artery. The possible pathophysiology is discussed.

Serum from atopics hypersensitive to the American cockroach were examined for their specific IgE to American and German cockroaches by the fluoroallergosorbent test (FAST). Of 44 sera tested, 86.4% (38/44) contained IgE to American and German cockroaches, and 13.6% (6/44) were found to be positive for American cockroach alone by FAST. Nine individual sera containing IgE antibodies to both cockroaches were used to analyze the cross-reacting allergens in the crude American and German cockroach extracts by FAST inhibition and immunoblotting. FAST-inhibition studies showed various degrees but similar inhibition of binding of human IgE to solid-phase American cockroach extract. Proteins from both cockroach extracts were separated on SDS-PAGE followed by immunoblotting, and the results showed considerable heterogeneity in the IgE-binding patterns with each of the cockroach extracts for the same nine individual sera. Components with apparent molecular weights of 60, 52, 49, 38, and 12 kDa from both the American and German cockroaches were able to bind IgE antibody. These results suggest the presence of cross-reactive allergens in the American and the German cockroaches.

A previous article described the isolation of several lambdagt22A cDNA clones expressing the American cockroach (Periplaneta americana) Cr-PI allergens recognized by both human atopic IgE antibodies and anti-Cr-PI monoclonal antibodies (Wu, C. H., Lee, M. F., and Liao, S. C.(1995) J. Allergy Clin. Immunol. 96, 352-359). This article presents the nucleotide and deduced amino acid sequences of two cDNA clones encoding major allergens of P. americana. Clones C12 and C20 encode proteins of 685 and 631 amino acids with two potential N-glycosylation sites each. The predicted molecular weights for C12 and C20 cloned proteins are 79,300 and 75, 500 with isoelectric point values of 6.26 and 6.63, which are compatible with the determined sizes (Mr 78,000 and 72,000) and isoelectric point value (6.2) of the Cr-PI allergens of P. americana. A high degree of identity (69.1%), including several overlapped predicted central antigenic determinant residues, was found between two allergens. The anti-fusion protein antibody-based enzyme-linked immunosorbent assay was able to detect crude American cockroach extract, Cr-PI, recombinant proteins, and commercial cockroach extracts, which provides further evidence that two allergens share common antigen determinants. Recombinant allergens of clones C12 and C20 both showed 47.4% skin reactivities on 19 cockroach-sensitive asthmatic patients. Unexpectedly, although no sequence similarity was found to other known allergens, two aromatic amino acid-rich allergens were found to have a striking sequence identity to insect storage proteins (20.1-33.9%), insect juvenile hormone-suppressible proteins (30.9-36.4%), and arthropod hemocyanins (29.7-34.6%). Results suggested that two prominent allergens of P. americana are ancestrally related to these insect hemolymph proteins and represent a new group of proteins in the hemocyanin superfamily. These data will now facilitate epitope-mapping studies, and the recombinant allergens may be valuable for diagnostic and therapeutic purposes.

To study the relationship between the inhibiting effect on platelet aggregation and the enhancing effect on epoprostenol (PGI2) released from vascular endothelium with 3,4',5-trihydroxystibene-3-beta-mono-D-glucoside (polydatin, Pol).After having been incubated with Pol, the incubating medium was withdrawn from the bottles with newborn umbilical vein endothelial cells (VEC group, trypsin digesting method) and added to the platelets (washing method). The medium withdrawn from the bottles without VEC was designated as control group. Reduction of platelet aggregation rates (PAR, turbidity method) and changes of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) (radioimmunoassay method) in the supernatant of the aggregated platelets induced by thrombin were scrutinized.PAR in the control group showed no reduction, whereas PAR reduction (-10 +/- 10) and 6-keto-PGF1 alpha increase (108 +/- 30 ng.L(-1)) in the VEC group treated 10 min with Pol 0.41 mmol.L(-1) (vs that of distilled water, ie, 2 +/- 12 and 54 +/- 20 ng.L(-1)) occurred.Increase of PGI2 from VEC by Pol was involved in its (Pol's) inhibition effect of platelet aggregation.

To study the effect of 3,4',5-trihydroxystibene-3-beta-mono-D-glucoside (Polydatin, Pol) on rabbit arterial thrombosis.Rabbit arterial thrombosis was induced by vascular endothelial damage with trypsin.It was showed that the moist weights of the thrombus were 6.6 +/- 1.8 and 4.8 +/- 1.6 mg in Pol 5 and 10 mg.kg-1 groups, respectively, which was lighter than that in control (10.9 +/- 1.9 mg, P0.05, P0.01); the platelet aggregation was inhibited simultaneously. In vitro, Pol 0.30-1.15 mmol.L-1 reduced TXA2 produced in platelets. It did not affect the production of PGI2 in cultured human umbilical vein endothelial cells.Thrombosis was abated by Pol. The selective inhibition of production of TXA2 rather than PGI2, is one of the mechanisms involved.

Pathological observations on brain damage in baby rats with experimental copper deficiency were carried out and the following observations were made: 1. The cerebrum were decreased in size and weight, the cortex became thinner and the corpus striatum atrophic. 2. Vacuolar degeneration and swelling of the mitochondria in the extrapyramidal system within the corpus striatum resulted in axon damage and disintegration of the myelin sheath. 3. Proliferation of endoplasmic reticulum in the dark neurons, swelling and rupture of mitochondria in the light neurons, which can result in necrosis of both types of neurons. The damage due to copper deficiency could not be reversed by copper supplements in diet.

From 1977 till 1991, the diagnosis of systemic lupus erythematosus was made on 137 children aged 18 years or under in Chang Gung Memorial Hospital. The medical records were reviewed and the clinical data were analysed with emphasis on the morbidity and mortality of this disease. The clinical and laboratory characteristics were similar to the findings from most other reports. Renal failure accounted for 8% of the initial presentation. The non-infectious complications were, in the order of frequencies, hypertension, avascular necrosis of femoral head, cataract, encephalopathy, and venous thrombosis. Sepsis, cutaneous infection and urinary tract infection were the frequently encountered infectious complications. The major causes of death in childhood onset systemic lupus erythematosus were sepsis (42%) and renal failure (30.7%). Forty patients were lost to follow-up. The 5-year survival rate, calculated by life-table, was 76.3%.

A 40-year-old Chinese woman with systemic lupus erythematosus (SLE) developed labile blood pressure 3 years after her onset of high blood pressure. Pheochromocytoma was subsequently found and removed. Postoperatively her hypertension improved without change in her SLE activity. Our case demonstrates pheochromocytoma can be a cause of hypertension in SLE.

3,4,5-Trihydroxystibene-3-beta-mono-D-glucoside (PD) from Polygonum cuspidatum 0.05-0.45 mmol/L increased beat rate of myocardial cells from 100% to 112-220%. This action of PD 0.15 mmol/L was agonized by nisoldipine 0.1, propranolol 10 and phentolamine 1 mumol/L. PD (0.05, 0.15 mmol/L) decreased the lactate dehydrogenase (LDH) amount liberated by myocardial cells, from 98 +/- 11 IU/ml of deprivation of oxygen and glucose (DOG) to 55 +/- 16, 68 +/- 14 IU/ml (P less than 0.01) 6 h after injury of DOG; 77 +/- 9, 80 +/- 6 IU/ml (P less than 0.01) 9 h after injury of DOG. PD 0.15 mmol/L decreased the LDH amount liberated by myocardial cells, from 311 +/- 34 to 231 +/- 42 IU/ml (P less than 0.05) 9 h after injury of chlorpromazine (CPZ). It is suggested that PD can protect myocardial cells injured by DOG and CPZ.

Double diffusion is one of the most simple and widely used immunologic techniques. If performed properly, this test offers the unique advantage of not only enumerating the minimum number of antigen-antibody systems, but also indicating the relationship among various antigens. However, the reaction lines should be interpreted cautiously and over-reading be avoided.

Three myeloma proteins, IgG lambda, IgA lambda and IgM lambda, were identified by protein electrophoresis (PEP), immunoglobulin quantitation and immunoelectrophoresis (IEP). Preparative block electrophoresis was generally carried out as an initial step to separate the myeloma proteins. The myeloma proteins thus separated were then passed through either diethylaminoethyl (DEAE) ion exchange chromatography and recycled in a Sephadex G-200 column, or first through gel filtration and recycled in DEAE. An attempt to bypass the step of preparative electrophoresis in the separation of IgG myeloma protein by passing the serum directly into a DEAE column was proved to be inappropriate. The IgM myeloma protein had a marked tendency to cryoprecipitate and to form euglobulin, and this property was utilized to separate the crude myeloma protein. The purified myeloma protein fractions were concentrated and dialyzed with Ultrafiltration (Amicon) and retested for purity with PEP, double diffusion (DD) and IEP. Some special physiochemical properties which affected the purification procedures are discussed.

A 21-year-old woman had suffered from repeated vasculitis and panniculitis with fever and chills after following mosquito bites since age 7. These manifestations were confirmed with a direct mosquito bite test during her admission to another hospital at age 17. The patient presented to our hospital with progressive dyspnea, productive cough and intermittent fever for one week. In addition to the bilateral infiltrative lesions on chest roentgenography, hepatosplenomegaly with an abnormal liver function test, pancytopenia, and elevated IgE were also detected. Blood and sputum cultures grew no microorganisms. Epstein-Barr virus-IgM, Cytomegalovirus-IgM and Mycoplasma pneumonia antibodies were all negative. Bone marrow aspiration and biopsy revealed histiocytosis with hemophagocytosis. No atypical histiocyte was found. The patient was put on dexamethasone treatment with improvement. Unfortunately, symptoms relapsed two weeks later. A repeated bone marrow aspiration and biopsy revealed a picture similar to the previous one. Despite antibiotic administration and ventilator support, a rapidly deteriorated course terminated in the patient's death by respiratory failure. Mosquito bite allergies were reported to be associated with malignant histiocytosis in Japan. However, atypical histiocytes were not found in our case upon repeated bone marrow aspirations, biopsies and skin biopsies. Mature histiocytes with hemophagocytosis were prominent instead. Reactive histiocytosis was thus favored rather than malignant histiocytosis. Although opportunistic infection cannot be excluded, we propose that a mosquito bite allergy with consequent histiocytic activation by antigen, immune complex or IgE is the possible pathogenetic mechanism for hemophagocytic histiocytosis in this patient.

Twelve human monoclonal immunoglobulins were separated and purified through the use of cryoprecipitation, salt fractionation, electrophoretic separation and gel filtration. Monoclonal cryoglobulin was the easiest form of homogeneous immunoglobulin to isolate. IgG and IgM were generally purified by salt precipitation and ion exchange chromatography followed by G-200 gel filtration. IgA purification required tedious recycling procedures. The purification of IgD posed the most difficulty as it may degrade spontaneously. Monoclonal immunoglobulins differed markedly in their behaviour towards enzymatic digestion, due to a rather wide specificity of enzymes on the Fc fragment. IgG was usually enzyme-sensitive, while some IgA proteins were virtually enzyme-resistant. The Fab fragment usually retained its antigenicity, but Fc or Fc' often split into small peptides. The reductive cleavage of monoclonal proteins usually gave consistent results, and H and L chains were separated in all experiments. However, 5 to 15% of IgA was at times eluated in unreduced form, and the alpha chain was often filtered as a dimer form. L chains were always eluated as a monomer form.

Immunoelectrophoresis is a combined technique of electrophoresis and double diffusion. The test has been widely used to enumerate and analyze the antigenic components in mixtures, and it is indispensable in the study of monoclonal gammopathy. The interpretation of reaction lines needs basic immunochemical knowledge about immunoglobulin and principles of immunoprecipitation. When properly performed, immunoelectrophoresis will, in most instances, confirm the diagnosis and establish the class and type of M protein. However, the reaction lines should be interpreted cautiously, and the immunoelectrophoretic pattern must be correlated with that of electrophoresis and also with the immunoglobulins levels. The basic immunoelectrophoretic patterns of most frequently encountered monoclonal gammopathies are presented and some of the difficult problems are discussed in this report.

The effect of ethanol on kinetic stages of natural killer (NK) cell activity was studied in vitro. Peripheral blood mononuclear cells (MNC) were either co-cultured or pre-incubated with various ethanol concentrations and assayed for NK cell activity with a "4-hour chromium release assay" and a "single cell cytotoxicity assay in agarose" simultaneously. Direct addition of ethanol to the assay system resulted in a dose-dependent inhibition of NK cell activity. The percentage of lysed conjugated target cells was suppressed from a control value of 21.2% to 17.0%, 15.1%, 11.8% and 10.0% with an ethanol concentration of 0.125%, 0.25%, 0.5% and 1.0%, respectively. NK cell recycling was also inhibited. A 24-hour pre-incubation with ethanol, however, resulted in NK cell activity enhancement. The enhancement was around 20% with a 0.25% ethanol concentration and around 45% with a 0.5% and a 1.0% ethanol concentrations. The enhancing effect was noted mainly at the cytolysis stage after binding of effector cell with target cells.

We present the first report of neonatal lupus erythematosus from Taiwan. A female baby, born to a mother with documented systemic lupus erythematosus (SLE), developed cutaneous lupus lesions after phototherapy for hyperbilirubinemia. She had additional clinical features of hemolytic anemia and thrombocytopenia. Detailed serological and immunogenetic studies were performed. Transplacental passage of both anti-SSA/Ro and anti-SSB/La antibodies were demonstrated and their disappearance at the age of 6 months correlated with regression of clinical symptoms. This patient inherited human leukocyte antigen (HLA) A11, Bw60 Cw3, DR2 and Aw33, Bw57, Cw7, DRw6 from her father and mother, respectively. A long-term follow-up is required for observing whether she will develop SLE in the future.

Multiple myeloma has rarely been reported in patients with ankylosing spondylitis. We observed a patient with a 20-year history of ankylosing spondylitis, who subsequently developed IgA myeloma. This association may not be simply coincidental. It has been proposed that the protracted stimulation of immunocytes by inflammatory lesions on the mucosal surfaces of the gastrointestinal, respiratory, and biliary tracts, where lymphocytes are already committed to IgA production, may be implicated in the pathogenesis of IgA myeloma in some patients. Ankylosing spondylitis is a chronic inflammatory disease, probably resulting from the interaction of a genetic predisposition involving HLA-B27 with an environmental event such as enteric bacterial infection. We propose that ankylosing spondylitis and IgA myeloma occurring concomitantly in our patient implies a possible pathogenetic relationship. In ankylosing spondylitis, persistent reticuloendothelial stimulation, due to chronic subclinical gastrointestinal infection, may lead to IgA-producing plasma cell activation and proliferation, and subsequent IgA myeloma development.

A 35-year-old male uremic patient developed the classical presentation of Reiter's syndrome after 3 years of regular hemodialysis. He had painful swelling of the left knee, sacroilitis, urethritis, balanitis, painless oral ulcers, acute uveitis and positive HLA-B27. Disease activity persisted and was aggravated although immune function studies showed depressed cellular immunity. The clinical course of this patient seemed to contradict our belief that activity of immunologically mediated disease will abate after uremia, but it concurred with the report that Reiter's activity was unchanged in AIDS despite the significant immunodeficiency of AIDS patients.

Simultaneous studies of serum and urinary proteins in 294 adult proteinuric patients are presented. Our data showed that these studies can provide valuable guides for clinical diagnosis. In the group of idiopathic nephrotic syndrome, hypoalbuminemia, hypogammaglobulinemia and hyper-alpha 2 globulinemia were most marked. Urinary protein electrophoresis (PEP) showed a well-selective pattern with albumin and beta globulin as the main constituents. In the other groups of proteinuric patients the hypoalbuminemia and hyper-alpha 2 globulinemia were milder and urinary PEP generally showed non-selective pattern. In the groups of acute glomerulonephritis and lupus nephropathy, C3 was generally decreased; polyclonal gammopathy was frequently encountered and alpha 1 acid glycoprotein was markedly increased. In the cases of chronic glomerulonephritis and diabetic nephropathy and the levels of gamma globulin, C3 and alpha 2 acid glycoprotein were usually within normal limits. Urinary protein selectivity index in this series of adult patients was not a useful diagnostic parameter.