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Relapsing polychondritis (RP) is an uncommon inflammatory disorder that predominantly targets cartilaginous structures. The disease frequently affects the nose, ears, airways, and joints, but it can also impact organs that aren't primarily cartilage-based, such as blood vessels, skin, inner ear, and eyes. Given its infrequent occurrence and recurrent symptoms, patients often experience delays in proper diagnosis. Lately, based on the organs involved, the disease's diverse manifestations have been categorized into specific clinical groups, based on the most likely organ involvement including auricular, nasal, pulmonary, and musculoskeletal. More recently the discovery of a new disease, called (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) VEXAS syndrome, due to mutations in UBA1 gene, identified the cause of 8 % of the patients with a clinical diagnosis of RP. VEXAS is likely the cause of a previously described "hematologic subgroup" in RP. This discovery is proof of concept that RP is likely more than one disease (Beck et al., Dec 31 2020; Ferrada et al., 2021). People diagnosed with RP face numerous hurdles, with the quality of their lives and overall prognosis being affected. Diagnosing the condition is particularly challenging due to its fluctuating symptoms, the absence of specific markers, and the lack of universally recognized classification criteria. For a correct diagnosis, it's imperative for healthcare professionals to identify its unique clinical patterns. Moreover, there are no approved metrics to gauge the disease's severity, complicating patient management. This review seeks to equip clinicians with pertinent insights to better diagnose and attend to these complex patients., (Copyright © 2023. Published by Elsevier Ltd.)

Background: ABO-incompatible (ABOi) heart transplantation (HT) in infants has been used to reduce waiting list time and mortality with outcomes comparable to ABO compatible (ABOc). We sought to assess trends in ABOi listing and transplantation for infants within the United Network for Organ Sharing registry and to evaluate its influence on outcomes., Methods: We reviewed infants listed for HT in the United Network for Organ Sharing registry (2007-2018). We compared demographic and clinical characteristics, waiting list duration, graft survival, and 1-year freedom from rejection between patients listed for ABOi and ABOc. Cochran-Armitage trend test, univariate nonparametric statistical methods, and Kaplan-Meier curves were used to analyze the data., Results: During the study period, 2787 patients were listed for HT, 53% of whom were listed for ABOi. Median waiting list time for patients in blood group O receiving an ABOi transplant was significantly shorter (P < .0001). Among the 1862 patients who received HT, 15% were ABOi. The incidence of ABOi HT also increased over time. The pretransplant anti-A and anti-B titers in the ABOi group did not significantly affect outcomes. There was no difference in the incidence of rejection in the first year after transplant and no significant difference in posttransplant survival CONCLUSIONS: The number of infants listed and transplanted as ABOi has gradually increased over the past decade, with a significantly decreased waiting list time for ABOi transplants in blood group O. At 1 year after transplant, rejection was comparable between the ABOi and ABOc groups and there was no significant difference in survival., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration., Methods: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014)., Results: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group., Conclusions: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes., Methods: Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children < 2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients., Results: Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p < 0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p < 0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting., Conclusions: In the current era, primary listing for ABOi heart transplant has become routine for the majority of children < 2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline., Methods: We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437., Findings: Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed., Interpretation: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma., Funding: Health Research Council of New Zealand., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009-2013. Further investigation could help understand these patterns., Methods: This retrospective cohort study investigated pediatric cancer (0-19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990-2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location-allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases., Results: The AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15-19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p < 0.05). Twenty-three counties located >2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden., Conclusions: Regional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: A large proportion of deaths and many illnesses can be attributed to three modifiable risk factors: tobacco use, overweight/obesity, and physical inactivity. Health risk assessments (HRAs) are widely available online but have not been consistently used in healthcare systems to activate patients to participate in prevention programs aimed at improving lifestyle behaviors., Objectives: The goal of this study is to test whether adding telephone-based coaching to use of a comprehensive HRA increases at-risk patients' activation and enrollment into a prevention program compared to HRA use alone., Methods: Participants were randomized to either complete an HRA alone or in conjunction with a telephone coaching intervention. To be eligible Veterans had to have at least one modifiable risk factor (current smoker, overweight/obese, or physically inactive). The primary outcome is enrollment and participation in a prevention program by 6months. Secondary outcomes include change in a Patient Activation Measure and Framingham Risk Score., Discussion: This study is the first to test a web-based health risk assessment coupled with a health coaching intervention within a large healthcare system. Results from this study will help the Veterans Health Administration (VHA) implement its national plan to include comprehensive health risk assessments as a tool to engage Veterans in prevention. The results will also inform health systems outside VHA who seek to implement Medicare's advisement that health risk assessment become a mandatory component of care under the Affordable Care Act., (© 2016.)

The Accreditation Council for Graduate Medical Education requires medical training programs to monitor, track, and formally document a fellow's performance. If deficiencies are found, programs are expected to prepare and implement an effective plan of action for improvement and to ensure that graduates acquire the personal and professional attributes of an independent physician. We revised our evaluation policy and instituted a remediation protocol in 2008. Since that time, 130 pediatric anesthesia fellows have graduated. Seven fellows (5%) underwent departmental formal consultation for deficient behavior or poor performance. Of these 7 fellows, 4 underwent an individualized remediation program (IRP). A formal performance review and written contract, with specifically identified problems and general themes, recommendations for time-based successful behaviors, and clearly identified consequences for unsuccessful behaviors, was initiated for each fellow undergoing an IRP. All fellows who participated in this program completed their subspecialty training in pediatric anesthesia, and all eligible fellows have successfully achieved their subspecialty board certification. Our approach has the advantage of multimodality, time-based daily evaluations, and group discussions in the context of a Clinical Competency Committee. Utilization of an IRP as a metric for progress has features similar to effective cognitive behavioral therapy contracts and has ensured that our graduates are held to clearly delineated and specified skills and behaviors that allow them to work independently in the field of pediatric anesthesiology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Decisions regarding health care of the severely mentally retarded can be difficult. We present 2 cases of patients with severe mental retardation who lived in long-term care facilities. Both patients had progressive loss of renal function and eventually reached end-stage renal disease. In each case, the decision was made not to initiate dialysis. We discuss issues of dialysis and medical care of the severely mentally retarded and advocate using the principles of "best respect" and "best interest" in making medical decisions in this population.

We recently demonstrated that expression of BHMT in McArdle RH-7777 (McA-BHMT) cells increases apo B mRNA abundance, leading to parallel increases in apo B secretion. The ratio of unedited to edited apo B mRNA was unchanged by BHMT expression. Based on the observation that secretion of B48 is increased relative to B100 in McA-BHMT cells, current studies now include comparison of B48 and B100 synthesis and intracellular degradation. Minor differences in co- and posttranslational degradation were unable to account for relative increase in B48 secretion, and the disappearance kinetics of B48 were similar in McA-BHMT and control cells. Consistent with the increase in endogenous apo B mRNA in McA-BHMT cells, B48 synthesis is increased significantly. In contrast, synthesis of B100 was not significantly increased. We conclude that B48 is preferentially translated compared to B100 when endogenous apo B mRNA is increased., (Copyright 2000 Academic Press.)

The obese Zucker diabetic fatty male rat (ZDF/Gmi¿trade mark omitted¿-fa) has become a widely used animal model of NIDDM, in contrast to the obese ZDF females that rarely develop NIDDM. However, preliminary observations suggest that obese ZDF females may become diabetic on high-fat diets. Therefore, we studied the effect of dietary fat on development of NIDDM, dyslipidemia, and alterations in organ-specific serum panels in obese ZDF males and females. Results indicated different effects of dietary fat-content on development of diabetes in males and females. Males, even on low fat-content diets, developed diabetes but the process was accelerated as a function of dietary fat-content, whereas only the highest fat-content diet induced development of NIDDM in obese ZDF females. Additionally, triglyceride/apolipoprotein B ratios demonstrated gender-specific differences in the nature of circulating lipoprotein particles independent of diabetic state with values for females approximately twice those of males indicating more highly triglyceride-enriched lipoprotein particles in females. We conclude that the obese ZDF female rat has the potential to become an important animal model of NIDDM especially in women where few models currently exist.

Apolipoprotein B (apoB) mRNA editing involves a site-specific cytidine to uridine transition catalyzed by the cytidine deaminase, APOBEC-1, in the context of and regulated by a multi-protein-containing editosome. ApoB mRNA editing in vivo is subject to tissue specific, developmental and metabolic regulation. We demonstrate for the first time that the amount of edited apoB mRNA in rat primary hepatocytes is markedly increased subsequent to transient treatment with ethanol in vitro. The apparent change in editing efficiency was dose-dependent (from 0.1%-2.4% initial ethanol dose) and occurred with rapid onset. The proportion of edited apoB mRNA was also markedly enhanced in a rat hepatoma cell line, McArdle RH7777 cells and in a stable McArdle cell line over-expressing APOBEC-1 by transient treatment with 2.5 % ethanol. In contrast, the apoB mRNA editing in a human hepatoma cell line, HepG2 cells and a stable HepG2 cell line over-expressing APOBEC-1 did not respond to ethanol treatment. The data support the possibility that editing activity is ethanol-responsive but suggest that this change is cell type-specific., (Copyright 1998 Academic Press.)

Apolipoprotein B (apo B) secretion is reduced by insulin in rat hepatocytes. To evaluate possible mechanisms by which insulin action leads to inhibition of apo B secretion, we evaluated the effect of suppression of the protein-tyrosine phosphatase LAR on apo B secretion by McA-RH7777 (McA) rat hepatoma cells. A reduction in cellular LAR levels was accomplished by stable transfection of McA cells with LAR antisense cDNA. Previous studies indicate that LAR-antisense transfectants demonstrate increased insulin receptor signaling. In current studies, reduced LAR expression results in a 60% to 70% reduction in apo B secretion compared with null vector control. The reduction in apo B secretion correlated with a significant decrease in cellular apo B mRNA levels. Results suggests there is a relationship of protein tyrosine phosphorylation with regulation of apo B mRNA abundance in McA cells.

Physical growth of preterm infants relates to many medical factors, such as birthweight, severity of medical illnesses, and nutritional status. We previously reported that maternal behaviors influence developmental outcomes in low birthweight infants (birthweight < 1600 g); we now hypothesize that maternal behaviors also influence physical somatic growth in low birthweight (LBW) infants. We serially followed 218 mother-infant pairs from birth through 12 months of age. One-hundred thirteen LBW infants were categorized based on severity of early medical complications. Low Risk infants (LR, n = 71) had acute respiratory distress and/or grade 1-2 intraventricular hemorrhage (IVH), or grade 3 IVH without hydrocephalus. High Risk infants (HR, n = 42) had chronic lung disease, grade 3 IVH with hydrocephalus or grade 4 IVH, and/or periventricular leukomalacia. We also studied 105 socioeconomic (SES) matched Full Term (FT) controls. Maternal behaviors were assessed during home visits with global ratings of Warm Sensitivity and Punitiveness. Infant weight was measured at birth and at 38 weeks, 6 months and 12 months corrected gestational age. We examined alternative expressions of weight growth across the three groups by developing the Weight Quotient (WQ), which is the ratio of actual measured weight to the median weight for age. For each infant the regression of the WQ ratio against correct gestational age was analyzed. We used a General Linear Model to compare the relation of the maternal variables to the weight quotients for the three groups. We determined the catch up growth as the slope of each regression. Results indicated that higher levels of maternal Punitiveness were related to slower rates of growth for High Risk (R2 = 0.36), but not Low Risk or Full Term. For maternal Warm Sensitivity (R2 = 0.36), there were significant (P < 0.05) inverse relations with weight gain growth for the Full Term infants. These data suggest that some maternal behaviors are related to the growth of term and premature infants, although the mechanisms through which this occurs is unclear.

Hepatocytes derived from lean Zucker rats have reduced secretion of apo B and lowered cellular apo B in response to a physiologic range of insulin (0.1 nM-10 nM). Effects are attenuated in hepatocytes derived from Zucker obese rats and seen only at higher insulin concentrations (> 100 nM) with a significant shifting of the dose-response curve. Decreased sensitivity and responsiveness of hepatocytes derived from obese rats suggests insulin resistance and dose-response curves are consistent with coexistent binding and post-binding defects. Inability to inhibit hepatic apo B secretion in the presence of short-term high levels of insulin may have important implications to the balance of intestinal and hepatic triglyceride-rich lipoprotein secretion post-prandially.

In primary cultures of rat hepatocytes, prostaglandin E2 and prostaglandin D2 (PGE2 and PGD2) inhibited the secretion of very low density lipoprotein (VLDL)-associated apoB, triacylglycerol, and cholesterol. These effects were concentration-dependent and remained apparent for at least 3 days of culture without an effect on the apoB/triacylglycerol ratio of the secreted VLDL. Prostaglandins had no effect on the overall synthesis of triacylglycerol but triacylglycerol accumulated within the cells, without intracellular accumulation of apoB. PGE2, when added to the medium together with glucagon, increased the inhibition of VLDL secretion, compared to that observed with glucagon alone. However, PGE2 did not increase the stimulatory effect of glucagon on ketogenesis. Unlike glucagon, the prostaglandins did not inhibit fatty acid synthesis nor did they stimulate ketogenesis or production of cAMP. Thus, of all the parameters of hepatic lipid metabolism studied, PGE2 and PGD2 selectively affected VLDL. Selective inhibition of VLDL secretion was also observed with the calcium antagonist verapamil. The divalent cation ionophore A23187 also inhibited VLDL release but, in contrast, also inhibited fatty acid and cholesterol synthesis. The results suggest that VLDL secretion is modulated at some optimal cell calcium concentration that may be mediated selectively by agents such as prostaglandins.

The mRNA for apolipoprotein B is translated into either a high molecular weight (apo BH) or low molecular weight (apo BL) form of the protein depending on a novel form of RNA processing known as RNA editing. Apo BH mRNA editing is both tissue-specific and hormonally regulated and involves transition of cytidine to uridine at codon 2153 thereby converting a glutamine codon (CAA) to a translational stop codon (UAA). Three methods for quantitating the endogenous levels of liver apo B mRNA editing were compared: (1) Southern blot hybridization with discriminative thermal washes, (2) competimer-hybridization with discriminative thermal washes and (3) competimer-polymerase chain reaction (competimer-PCR). The data suggest that hybridization and PCR can yield similar quantitation when competing oligonucleotides are used. Based on competimer-PCR it is proposed that 40% and 85% of normal rat liver and small intestine apo B mRNA (respectively) are edited.

This study compared substrate utilization by the fetal hind limb and the maternal hind limb in 26 sheep at 120 to 135 days of gestation. Catheters were placed in the mother and the fetus to sample femoral arterial and venous blood by use of a nonocclusive technique. Arterial and venous concentrations of oxygen content, glucose, lactate, acetate, and ketoacids were measured simultaneously and were used to calculate metabolic quotients. The fetal hind limb was perfused with arterial blood having a lower oxygen content than the maternal hind limb (3.03 +/- 0.17 versus 4.94 +/- 0.24 mmol/L, p less than 0.001) and had a smaller arteriovenous difference of oxygen content (0.97 +/- 0.05 versus 2.68 +/- 0.104 mmol/L, p less than 0.001). Despite a lower fetal arterial glucose concentration (0.81 +/- 0.05 versus 2.58 +/- 0.13 mmol/L, p less than 0.001), the glucose/oxygen quotient (0.82 +/- 0.05 versus 0.20 +/- 0.02, p less than 0.001) and the arteriovenous difference of glucose (0.13 +/- 0.01 versus 0.08 +/- 0.01 mmol/L, p less than 0.001) were higher in the fetal hind limb than in the maternal hind limb. Both limbs were net producers of lactate. The (glucose + lactate)/oxygen quotient was also higher in the fetal hind limb than in the maternal hind limb (0.68 +/- 0.05 versus 0.12 +/- 0.04, p less than 0.001). In the maternal hind limb, acetate and ketoacids uptake could account for 48% +/- 6% of total oxygen consumption whereas in the fetal hind limb it accounted for only 12% +/- 4% (p less than 0.001). The data demonstrate that, in relation to oxygen uptake, fetal hind limbs have approximately a 2.8% higher rate of perfusion and take up approximately four times as much glucose as the hind limbs of the mother in the resting state.

Bethamethasone was administered to pregnant rhesus monkeys of 134 to 150 days' gestation. At operative delivery, umbilical venous plasma cortisol concentrations were significantly lower in the treated group than in the control group, indicating that the agent crossed the placenta. In the treated group, accelerated differentiation was present in several fetal organs including lung, liver, kidney, and adrenal gland. Brain histologic changes suggestive of neuronal injury were found in some instances. There were no differences in the weights of these fetal organs except for liver. It was markedly increased in steroid-treated fetuses and this was accompanied by a fourfold rise in total hepatic glycogen content. These observations suggest that in the subhuman fetal primate, the differentiation of fetal organs in addition to lung is enhanced by short-term corticosteroid treatment while growth is not affected.

Murine hybridomas were prepared by fusion of azaguanine-resistant plasmacytoma cells and spleen cells from BALB/c mice immunized with intact rat lipoproteins (Lp). Seventeen stable hybridomas from 5 fusions producing antibody against rat apolipoprotein B (apo B)-containing Lp were prepared. The distribution of antigenic determinants of rat apo B variants defined by these antibodies was similar to that found for human apo B. Thirteen mAbs were reactive to epitopes found on both the higher (apo BH) and lower (apo BL) molecular weight forms of rat apo B; two were reactive to apo BH-specific epitopes and two were reactive to apolipoprotein E. No antibodies reactive to unique apo BL epitopes were found. One anti-rat apo B mAb (1.34.3) of high affinity and avidity was reactive to denatured and intact Lp-apo B. Reactivity towards Lp-apo B was independent of variant composition and density class of Lp. The mAb was subsequently used to develop a radioimmunoassay (RIA) which was sensitive down to 5 ng apo B. The assay was used successfully to measure total nascent Lp-apo B secreted by hepatocytes in culture.

The complete sequence of recombinant human interleukin-2 expressed in Escherichia coli has been confirmed by thermospray liquid chromatography-mass spectrometry (TS-LC-MS) of a tryptic digest derived from 100 micrograms (7 nmol) of reduced carboxymethylated interleukin-2. The preparation was shown by this method to contain predominantly unprocessed N-terminal initiator Met, with some authentic N-terminal Ala; the rest of the protein was as predicted from the DNA sequence, though some deamidated material was noted. TS-LC-MS proved to be a rapid and efficient method for surveying the protein tryptic peptide products allowing all the data to be collected in one chromatographic run; all tryptic fragments were identified by their molecular ions including those for the larger peptides (Mr 1500-3500) which, due to the presence of doubly and triply charged molecular ions, were brought within the mass range of the instrument (1800 Da). It is proposed that TS-LC-MS is a good general method for analyzing recombinant protein digests with respect to sequence confirmation, processing, and post-translational modification, and since each chromatographic peak is identified allows for subsequent monitoring of the protein by LC using uv detection. The method suffers from the disadvantages that all the sample is consumed during the experiment and that no fragment (sequence) ions are generally observed.

Recombinant Interleukin-2 (IL-2) is expressed in E. coli as insoluble aggregates; a protocol has been developed for solubilization, renaturation and purification of IL-2 from such aggregates at the 5-10-mg level. IL-2 aggregates were isolated from soluble proteins by centrifugation, subjected to a 1 M guanidine hydrochloride wash and a butan-1-ol wash (the latter to remove lipid), dissolved in 8 M guanidine hydrochloride-10 mM dithiothreitol and partly purified by gel permeation chromatography. Refolding/oxidation was then performed by dilution into Tris-HCl, pH 8.5 containing 1.5 microM copper sulphate to accelerate autoxidation. Final purification was by successive cation-exchange and reversed-phase high-performance liquid chromatographic steps, yielding over 99.5% pure IL-2 with an overall recovery of 20%.

A study of routine data on mumps in England and Wales suggests that its epidemiological features are changing from those of an epidemic disease in young adults and older children to a more endemic disease in younger children. Infection now occurs at an earlier age, at which complications are less frequent and symptomless infection may be more common. The incidence of clinical disease may be falling. The high proportion of registered deaths in the middle aged and elderly may be an artifact due to misclassification of causes of death and to misdiagnosis. These changes lessen the need for routine immunisation. Indeed with low acceptance rates of measles vaccination of 50% at age 15 months, mumps/measles routine vaccination at the same age is contraindicated because similarly low acceptance rates might lead to an increase in the number of cases of mumps in older children and young adults, at which ages complications are more frequent.

This study was designed to evaluate the role of dietary sucrose and lactose in a semipurified diet as initiating factors for aortic glycosaminoglycan (GAG) and lipid changes. Rabbits were fed sucrose or lactose as 40% by weight of a semi-purified, cholesterol-free diet for 10 weeks. At the end of the feeding period there was no macroscopic evidence of atherosclerosis. Sucrose-fed rabbits had significantly higher plasma cholesterol and phospholipid levels than the lactose-fed rabbits and triglyceride levels were variably elevated in the sucrose group. Analysis of plasma lipoproteins indicated that sucrose elevated VLDL and LDL when compared to lactose. Only the higher molecular weight form of apo B (apo BH) could be demonstrated when apo B components of isolated lipoproteins were analyzed. Sucrose-fed rabbits had significantly more aortic cholesterol, cholesteryl ester and phospholipid and tended to have more GAG/mg dry defatted aorta than the lactose-fed rabbits. Plasma cholesterol levels correlated with aortic lipids and in the sucrose group, aortic cholesteryl ester and cholesterol were strongly correlated with aortic GAG particularly hyaluronic acid. Results suggest that the semi-purified diet alters aortic GAG composition but in order for the initiation of cholesterol accumulation a significant increase in plasma lipoprotein cholesterol is necessary.

The antihypertensive action of renomedullary autotransplantation was investigated in rats with unilateral hereditary hydronephrosis showing extensive destruction of the medulla of the affected kidney. All rats were divided into three groups and unilaterally nephrectomized. The first group consisted of rats with a normal kidney remaining. The second and third groups had the hydronephrotic kidney remaining and received renomedullary and renocortical autotransplants, respectively. After completion of baseline studies, all rats were given 1 per cent saline solution instead of drinking water, and relevant parameters were re-examined 14 days later. Significant increase in blood pressure (greater than 150 mm. Hg), extracellular fluid volume, and plasma volume were found in group 3 while no changes were detected in groups 1 and 2. After administration of aspirin (and presumed blockade of prostaglandin synthesis) significant increases in plasma and extracellular fluid volumes were detected in groups 1 and 2, but no change in blood pressure was found. The results show that renomedullary transplantation protects against salt-induced hypertension and further indicate that the renomedullary prostaglandins are not a likely mediator of the antihypertensive action of the renal medulla.