New ABO intron 1 variant alleles.

Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(29-5G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factor-binding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(29­5G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factor­binding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.

An excess of small-scale gravitational lenses observed in galaxy clusters.

Cold dark matter (CDM) constitutes most of the matter in the Universe. The interplay between dark and luminous matter in dense cosmic environments, such as galaxy clusters, is studied theoretically using cosmological simulations. Observations of gravitational lensing are used to characterize the properties of substructures-the small-scale distribution of dark matter-in clusters. We derive a metric, the probability of strong lensing events produced by dark-matter substructure, and compute it for 11 galaxy clusters. The observed cluster substructures are more efficient lenses than predicted by CDM simulations, by more than an order of magnitude. We suggest that systematic issues with simulations or incorrect assumptions about the properties of dark matter could explain our results.

A data-driven patient blood management strategy in liver transplantation.

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.

Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.

BACKGROUND: Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). PATIENTS AND METHODS: CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. RESULTS: The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. CONCLUSIONS: This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM(+)) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.

Drug-induced toxicity and patient reported outcomes in rheumatoid arthritis patients following intensive treated-to-target strategy: does ceasing therapy due to toxicity worsen outcomes in long term?

AIM: While the introduction of the treat-to-target (T2T) strategy has been an important advance in the management of rheumatoid arthritis (RA), the potential for increased toxicity due to use of concurrent drugs could adversely affect patient reported outcomes (PROs). The objective was to determine whether the cessation of therapy due to toxicity affects long-term improvement in PROs in patients treated according to T2T strategy. METHODS: A total of 149 patients from an inception cohort of early RA were included. The occurrence and severity of toxicity were monitored at each visit over 3 years. PROs studied were function (measured using health assessment questionnaire); pain, fatigue and patient global assessment (PtGA) all assessed using a 100 mm visual analogue scale; helplessness and health-related quality of life (HRQoL). For each PRO, effect of drug withdrawal was measured by comparing mean change in PROs among patients with no/temporary vs. permanent withdrawal. In addition, effects of frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression. RESULT: After 3 years, 56 (37.4%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n = 93) achieved significantly greater improvement in function (mean change = -0.54 vs. -0.31, p = 0.033), pain (mean change = -39.82 vs. -5.02, p = 0.018), fatigue (mean change = -29.14 vs. -14.76, p = 0.015) and PtGA (mean change = -29.64 vs. -17.00, p = 0.018) compared with their counterparts. Higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PtGA, while the number of drugs withdrawn and the weeks to withdrawal had lesser effects. However, the cessation of the drugs due to their toxicity did not have a significant association with HRQoL and helplessness. CONCLUSION: Improvements in function, pain, fatigue and PtGA at 3 years were diminished for patients who ceased drugs due to toxicity while broader measures of HRQoL were not affected.

Thrombosis in ovarian cancer: a case control study.

BACKGROUND: Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies. METHODS: A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis. RESULTS: Ninety-nine thrombotic events occurred in 90 patients (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking in the 4 months following diagnosis. Patients with thrombosis were older (mean 65 vs 61 years, P=0.007), had a worse performance status (PS ≥2: 29.9% vs 9.5%, P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%, P<0.0001) than patients without thrombosis. Shorter overall survival was seen in patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than without thrombosis (P=0.001). When the control group was matched for stage and PS, no survival difference was seen (P=0.91). CONCLUSION: Ovarian cancer patients with thrombotic events had a shorter survival. However, when matched for prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.

U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

New constraints on macroscopic compact objects as dark matter candidates from gravitational lensing of type Ia supernovae.

We use the distribution, and particularly the skewness, of high redshift type Ia supernovae brightnesses relative to the low redshift sample to constrain the density of macroscopic compact objects (MCOs) in the Universe. The supernova data favor dark matter made of microscopic particles (such as the lightest supersymmetric partner) over MCOs with masses between 10(-2)Mo and 10(10)Mo at 89% confidence. Future data will greatly improve this limit. Combined with other constraints, MCOs larger than one-tenth the mass of Earth (approximately 10(-7)Mo) can be eliminated as the sole constituent of dark matter.

A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats.

OBJECTIVES: To assess the effects of providing a wide range of foodstuffs containing n-3 polyunsaturated fatty acids (PUFA), occurring naturally or from fortification, on intake and blood and tissue proportions of n-3 PUFA. DESIGN: Before/after dietary intervention study. SETTING: Adelaide, Australia. SUBJECTS: 16 healthy males recruited from the community. INTERVENTIONS: Subjects were provided with a range of foodstuffs naturally containing n-3 PUFA (fresh fish, canned fish, flaxseed meal, canola oil) and items fortified with fish oil (margarine spread, milk, sausages, luncheon meat, french onion dip). Food choices were left to the discretion of each subject. Intake was estimated by diet diary. Blood was collected at-2, 0, 2, and 4 weeks for fatty acid analysis. MAIN OUTCOME MEASURES: Dietary intakes; plasma, platelet, and mononuclear cell phospholipid fatty acids. RESULTS: Consumption of n-3 PUFA increased significantly: alpha-linolenic acid (ALA) from 1.4 to 4.1 g/day (P<0.001), eicosapentaenoic acid (EPA) from 0.03 to 0.51 g/day (P<0.001), and docosahexaenoic acid (DHA) from 0.09 to 1.01 g/day (P<0.001). Linoleic acid (LA) intake decreased from 13.1 to 9.2 g/day (P<0.001). The proportions of EPA and DHA increased significantly in all phospholipid pools examined; plasma EPA from 1.13% of total fatty acids to 3.38% (P<0.001) and DHA from 3.76 to 7.23% (P<0.001); mononuclear cell EPA from 0.40 to 1.25% (P<0.001) and DHA from 2.33 to 4.08% (P<0.001); platelet EPA from 0.41 to 1.2% (P<0.001) and DHA from 1.64 to 3.07% (P<0.001). CONCLUSION: Incorporating fish oil into a range of novel commercial foods provides the opportunity for wider public consumption of n-3 PUFA with their associated health benefits. SPONSORSHIP: Dawes Scholarship, Royal Adelaide Hospital.

Front line workers in long-term care: the effect of educational interventions and stabilization of staffing ratios on turnover and absenteeism.

OBJECTIVE: Front line workers in long-term care play a crucial role in helping residents achieve their highest possible functional level. High turnover (rates in excess of 100% are common) and absenteeism threaten the ability of long-term care providers to meet this goal. The purpose of this study was to determine the effect of a formalized certified nursing assistant (CNA) education program and stabilization of staffing ratios on turnover and absenteeism. DESIGN AND SETTING: This study was a 12-month prospective, nonrandomized trial involving two long-term care facilities providing traditional intermediate and skilled care serving as study sites and a similar facility serving as a control. For historical comparisons, each facility served as its own control using data from the year before the interventions. INTERVENTIONS: An in-house educational program based on the State of North Carolina core curriculum for CNAs was instituted in each study site. During the study period, efforts were made to achieve stable staffing ratios of 1 CNA:8 residents for days, 1:10 for evenings, and 1:15 for nights. Traditional quality of care indicators and resident/surrogate satisfaction were tracked during the study period. RESULTS: Both study facilities showed a decline in turnover, with the decline reaching statistically significant levels at Facility B (134% to 41%, P = 0.0001). Absenteeism rates did not change significantly during the study period. Resident/surrogate satisfaction with nursing care was improved significantly at Facility B (P = 0.02). CONCLUSION: A formal education program in conjunction with stabilization of staffing ratios can result in lower turnover rates for CNA's and improved resident/surrogate satisfaction.

Maternal and developmental toxicity of halogenated 4'-nitrodiphenyl ethers in mice.

In an ongoing effort to delineate structure-activity relationships in the developmental toxicity of diphenyl ethers, we evaluated the maternal and developmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen. All possible trichlorophenyl 4'-nitrophenyl ethers were evaluated, as were the 2,4-difluorophenyl and 2,4-dibromophenyl 4'-nitrophenyl ethers. We also evaluated bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl congeners with meta-substituents on the 4'-nitrophenyl ring. Nitrofen (2,4-dichlorophenyl 4'-nitrophenyl ether) was included for comparison. Identity of the halogen affected the postnatal (but not prenatal) mortality induced by 2,4-dihalogenated 4'-nitrophenyl ethers. The presence of 3'-substituents on the 4'-nitrophenyl ring reduced both pre- and postnatal toxicity of 2,4-dichlorinated congeners. Among chlorinated 4'-nitrophenyl congeners without meta-substituents on the nitrophenyl ring, the position of chlorine substituents strongly affected the congener's potential for inducing prenatal vs. postnatal syndromes. All congeners increased liver to body weight ratios in unmated females, but such increases were not well-correlated with either prenatal or postnatal embryotoxicity.

Enhancement of solar water pasteurization with reflectors.

A simple and reliable method that could be used in developing countries to pasteurize milk and water with solar energy is described. A cardboard reflector directs sunshine onto a black jar, heating water to pasteurizing temperatures in several hours. A reusable water pasteurization indicator verifies that pasteurization temperatures have been reached.

A multifaceted study of human papillomavirus and prostate carcinoma.

BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.

The use of breastmilk in a neonatal unit and its relationship to protein and energy intake and growth.

OBJECTIVE: A nutritional audit was performed to determine whether current feeding regimes were achieving nutritional goals and to evaluate the use of breastmilk (BM) in a neonatal unit (NNU). METHODS: All fluid consumed or infused daily was documented with daily weight and weekly length and head circumference measurements in 90 preterm infants (gestational age 30.1 +/- 2.6 weeks) while in the NNU for 60 +/- 27 days. Daily protein and energy intakes were calculated using values for South Australian preterm BM. RESULTS: Parenteral nutrition provided 85% of the daily energy in week 1 falling to 11% by week 6. Ninety per cent of infants received some of their mother's BM and 62% were discharged at least partially breastfed. Protein and energy intakes were 1.03 +/- 0.35 g and 55 +/- 10 kcal/kg/day in week 1, increasing to 2.52 +/- 0.60 g and 109 +/- 15 kcal/kg per day by week 4. Protein intake correlated with weight gain (r2 = 0.39). Weight gain was 14.0 +/- 2.0 g/kg per day and z-scores for weight declined from -0.25 on admission to -1.22 on discharge, P < 0.0001. When infants were divided into two groups comprising those who received BM or formula as their predominant enteral feed, growth and protein intake (but not energy intake) were lower in the BM-fed infants. However, enteral feeds were tolerated earlier and more quickly in those infants receiving predominantly BM. CONCLUSION: Energy requirements were readily met using current feeding regimes for preterm infants but protein intakes were marginal. Mothers of preterm infants had similar breastfeeding rates to mothers of term infants in South Australia. The long-term effects of the lower growth rates of preterm infants fed predominantly BM compared with those fed predominantly formula are unknown and need be balanced against the benefits of BM.

Caval thrombectomy for severe staphylococcal osteomyelitis.

Two children are presented in whom thrombosis of the inferior vena cava developed in association with an acute staphylococcal osteomyelitis. One case involved the left femur and the other the left ileum. Both children had diffuse bilateral staphylococcal pneumonia from presumed septic embolization. There were close similarities between their illness and management, except that the child who survived underwent a caval thrombectomy in the acute phase of her illness. It is hypothesized that the thrombectomy played an important role in her recovery.

Fifteen-year follow-up of arthroscopic partial meniscectomy.

From an original pool of 283 patients, 146 patients who had undergone arthroscopic partial meniscectomy an average of 14.7 years before were followed-up. Lysholm score, Tegner activity level, satisfaction index on a scale of 1 to 10, and standing anteroposterior and flexion weight-bearing radiographs of both knees, were obtained. A physical examination was performed on each knee emphasizing motion, swelling, and ligament evaluation. Radiographs were graded for degenerative changes for each knee. Each knee joint space was also measured in millimeters and compared, operative knee with unoperated knee. The unoperated knee had no injuries or surgeries and was used as a control. Patients were 83% male and 17% female; 78% had undergone medial meniscectomies, 19% lateral, and 3% both. There were 88% good and excellent results in anterior cruciate ligament-stable knees. The radiographic grade side-to-side difference showed the operative knee to be only a 0.23 grade worse than the nonoperative knee. Age at the time of meniscectomy was not found to be a factor. Male patients had better radiographic results than female patients, but not better functional scores. Medial meniscus and lateral meniscus results were not significantly different. Knees with a femoral-tibial anatomic alignment of > 0 degree valgus compared with < or = 0 degree and that had undergone medial meniscectomy had significantly better radiographic results. Patients with anterior cruciate ligament tears and meniscectomy did significantly poorer than stable knees with meniscectomy in regards to radiographic grade change, Lysholm, satisfaction index, Tegner level, and medial joint space narrowing.

Requirement for increased IL-10 in the development of B-1 lymphoproliferative disease in a murine model of CLL.

Malignant B-1 cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for the expansion of malignant B-1 cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-1 cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-1 malignant clones. In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically. IL-10 may enhance proliferation and the development of B-1 cell malignancy rather than antibody production by the B-1 cell subpopulation. Thus, IL-10 plays an important role in B-1 malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies.