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A potentially high bioavailability of arsenic in gold mine tailings from a site in northern California has been suggested by solubility studies. To help address this issue, an in vivo dosing study was conducted using 12-day-old Swiss Webster mouse pups (n=8/group). A sample of size-fractionated mine tailings from the site (<20 mum particle size, 691 mug g^-1 arsenic) was prepared as an aqueous suspension and administered by gavage in a volume that provided 4 mg As/kg body weight. The control group received the same volume of a commercial soil (1mug g^-1 As) of similar particle size (<60 mum). No mortality or toxic signs were noted in either group. Tissue samples were collected 1 h after gavage, freeze-dried, microwave-digested and analyzed for arsenic by ICP/MS (detection limit 2 ng As g^-1 dry weight). Arsenic concentrations (ng As g^-1 dry weight) in tissues from the pups who received mine tailings were significantly higher than in control tissues.The mean elevation in arsenic concentration was highest in the liver(3364% of control, p<0.0001), followed by blood (818 of control, p<0.0001), skin (207% of control, p=0.07), and brain (143% of control, p<0.0001). The carcass arsenic concentration (excluding the GI tract, liver, brain and skin) was 138 of control (p=0.02). The data indicateuptake of arsenic from weathered mine tailings by the immature mousepups after oral exposure. [ABSTRACT FROM AUTHOR]

mGluR2 receptors are widely expressed in limbic brain regions associated with memory, including the hippocampal formation, retrosplenial and frontal cortices, as well as subcortical regions including the mammillary bodies. mGluR2/3 agonists have been proposed as potential therapeutics for neurological and psychiatric disorders, however, there is still little known about the role of these receptors in cognitive processes, including memory consolidation. To address this, we assessed the effect of the mGluR2/3 agonist, eglumetad, on spatial memory consolidation in both mice and rats. Using the novel place preference paradigm, we found that post-sample injections of eglumetad impaired subsequent spatial discrimination when tested 6 h later. Using the immediate early gene c-fos as a marker of neural activity, we showed that eglumetad injections reduced activity in a network of limbic brain regions including the hippocampus and mammillary bodies. To determine whether the systemic effects could be replicated with more targeted manipulations, we performed post-sample infusions of the mGluR2/3 agonist 2R,4R-APDC into the mammillary bodies. This impaired novelty discrimination on a place preference task and an object-in-place task, again highlighting the role of mGluR2/3 transmission in memory consolidation and demonstrating the crucial involvement of the mammillary bodies in post-encoding processing of spatial information., (© 2024. The Author(s).)

Adverse childhood experiences (ACEs) are linked to later life health problems such as behavioral health (BH) service use but less is known about how to counter this association. Using a population based sample of 807 adults, we examined the effects of protective factors in countering this association. ACEs were associated with increased BH service use while protective factors were associated with decreased BH service use. However, no significant interaction effect was found. Research is needed to develop a better measure of protective factors. Social workers need to be aware of ACE prevalence among clients and can foster protective factors.

Prednisolone is a steroid belonging to the corticosteroid group. The results obtained in the application of the 2008 and 2009 Italian Residue Control Plans show the frequent detection of prednisolone traces in cow's urine. Since most of the positive samples were detected at the slaughterhouse, the researchers hypothesised that, together with an increase of cortisol concentration, traces of prednisolone could be produced endogenously during stressful situations due to transport and handling before slaughter. In the present trial, 52 lactating cows housed in seven different farms in Lombardy, Italy, were studied. Urine samples were collected at the farm (after urethral catheterisation) and immediately after slaughter (from urinary bladder) together with 40 adrenal gland samples belonging to the same animals. All the samples were analysed for the determination of prednisolone and cortisol by LC/MS(n). The results demonstrated that prednisolone can be endogenously produced in dairy cows and, furthermore, its endogenous presence in bovine urine seems to be strongly related to a state of stress in the animals (at the farm and at the slaughterhouse). The data from adrenal glands do not, however, clarify if the endogenous production occurs, partially or totally, in this organ.

This special edition of TRANSFUSION is dedicated to those colleagues in the transfusion medicine and cellular therapy field who have wondered about what the future holds for their chosen professions. Each of the six peer-reviewed Think Tank articles included in this special edition focuses on an administrative issue that is critical to the survivability and enhancement of the industry. Each issue is examined from two perspectives: Where are we now? And where are we heading?

The hallmark of T- and B-lymphocyte development is the rearrangement of variable (V), diversity (D), and joining (J) segments of T-cell receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse repertoire of antigen receptor specificities in the immune system. The process of V(D)J recombination is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibility to the recombinase apparatus in a lineage- and stage-specific manner. These chromatin changes are linked to transcription of the locus in its unrearranged (germline) configuration. To understand how germline transcription of the TCRbeta-chain gene is regulated, we determined the structure of germline transcripts initiating near the Dbeta1 segment and identified a promoter within this region. The Dbeta1 promoter is active in the presence of the TCRbeta enhancer (Ebeta), and in this context, exhibits preferential activity in pro-T versus mature T-cell lines, as well as T- versus B-lineage specificity. These studies provide insight into the developmental regulation of TCRbeta germline transcription, one of the earliest steps in T-cell differentiation.

We have used random sequence mutagenesis and complementation in a bacterial selection system to establish a large library of immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutants with amino acid substitutions in the beta3-beta4 region of the fingers subdomain [Kim, B., Hathaway, T. R., and Loeb, L. A. (1996) J. Biol. Chem. 271, 4872-4878]. We show here that one of these mutants, D76V, exhibits increased accuracy of copying both DNA and RNA templates in a primer extension assay with biased dNTP pools. More detailed analysis of DNA-dependent polymerization showed that the D76V mutation conferred an up to 14-fold increase in fidelity of nucleotide insertion and a 9-fold reduced mutation rate in an M13mp2 lacZalpha forward mutation assay. Substitution at D76 with positively charged (D76R) and nonpolar (D76V and D76I) residues increased replicational accuracy, while substitutions with negatively charged (D76E) and polar residues (D76S and D76C) had little effect on fidelity. We propose that D76 affects replicational accuracy by mediating interaction between the fingers subdomain and the single-stranded template. Our work shows that the Escherichia coli complementation system can yield HIV RT mutants with increased fidelity that have not been isolated from the natural host and that are valuable in understanding the molecular bases of replicational accuracy.

Objective: Because the optimal timing for follow-up of acute otitis media (AOM) is unknown and clinicians' recommendations for timing follow-up are highly variable, a study was conducted to determine which risk factors or symptoms could predict the resolution, recurrence, or persistence of AOM after treatment completion., Methods: Three hundred four children from a general pediatric practice in a staff-model health maintenance organization, ages 6 months to 4 years diagnosed with AOM were enrolled in a prospective study of the clinical outcome of AOM at 10 to 21 days from diagnosis. Risk factors, symptoms, and parental observations were obtained by questionnaire at both the initial and follow-up visit 10 to 21 days later. At the follow-up visit, the clinical outcome of resolved AOM or persisting AOM was determined by the examining clinician., Results: One hundred eighty-one patients returned for follow-up between 10 to 21 days; 24.9% had AOM at follow-up. Parental impression of resolved ear infection and the absence of symptoms at follow-up identified 97.1% of children with resolved AOM. Other factors associated with increased risk of AOM at follow-up were age < or = 15 months and a family history of recurrent AOM in a sibling., Conclusions: Because parental judgement of ear status and observation of symptoms appear to accurately identify those children with resolved AOM, a follow-up strategy is proposed in which posttreatment follow-up may be selectively offered to children whose parent(s) feels the infection has not resolved, children whose symptoms persist, or children at higher risk for AOM such as those < or = 15 months or with a family history of recurrent otitis.

Basic research has promise for clinical wound healing. Purified wound healing growth factors are not available for clinical use, but they are present in plasma and platelets and have been used in patients. Chronic wounds would seem to be good for study since the wound surface is easily measured and the patient is anxious for progress. We have done a double-blinded pilot study using autologous cryoprecipitate on chronic wounds. Three of six patients showed wound healing progress; but only one patient's wounds healed permanently. One patient developed new diabetic ulcers, and one patient failed to keratinize epithelialized skin. Cryoprecipitate may promote wound healing, but further work awaits more purified healing factors. Simple measurement of the surface area of a chronic wound may not be adequate to describe all the processes of healing.

We have studied the effects on FEV1 of inhaled capsaicin in concentrations of 3 x 10(-6) to 3 x 10(-1) mg/ml and methacholine (1 to 16 mg/ml) in 15 heart-lung transplant (HLT) patients who had undergone recent transbronchial lung biopsy to determine the relationships in chronically denervated lungs between these different forms of airway hyperreactivity and inflammation. A total of 10 normal subjects and 17 asthmatic subjects were included for comparison. Capsaicin caused bronchodilation in eight HLT patients (FEV1 rising by 6.4 to 26.8%) and bronchoconstriction in two (fall in FEV1 of 7.2 and 7.6%). By contrast, seven asthmatic subjects developed bronchoconstriction after capsaicin (fall in FEV1 5.6 to 40.4%); the remaining 10 asthmatic subjects showed no response. Bronchial hyperresponsiveness to methacholine was most evident in the asthmatic subjects, but six HLT patients demonstrated a > or = to 20% fall in FEV1 with < or = 8 mg/ml of methacholine. All normal subjects were nonresponsive to both agents, and all normal and asthmatic subjects, unlike HLT patients, coughed with capsaicin. No relationship existed between the methacholine and capsaicin responses. In the HLT patients neither form of airway responsiveness was related to the degree of inflammation seen on transbronchial lung biopsy. The results suggest that in normal subjects, although it provokes cough, inhaled capsaicin causes little airway narrowing.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart-lung transplantation is a successful treatment for patients with cystic fibrosis and chronic respiratory failure. Patients are assessed for surgery when life expectancy is deemed short. This study assesses the ability of measurements of pulmonary function, blood gas levels, and nutritional status to predict survival of patients awaiting heart-lung transplantation and to assess the effect of heart-lung transplantation on survival. Sixty-seven patients with cystic fibrosis were accepted for heart-lung transplantation from 1985 through 1990. Each patient underwent tests of pulmonary function, exercise tolerance, blood-gas levels, and nutritional status. Cox regression was used to analyze the prognostic value of these data. Of the 67 patients accepted for heart-lung transplantation, organs became available for 30; 24 patients died waiting, and 13 patients were on the list December 31, 1990. Eight patients died after transplantation. Patients with above-average forced expiratory volume in 1 second (FEV1) (median, 17% predicted) at assessment were half as likely to die waiting (relative risk, 0.47; 95% confidence interval, 0.23 to 0.97) as patients with below-average FEV1. The relative risk of death for patients on the waiting list was 1.44 (95% confidence interval, 1.17 to 1.77) for each increment in PCO2 of 1 kPa. No effect of nutritional status on waiting list death was found, but seven of eight patients who died after heart-lung transplantation were below 80% predicted weight for height. Using a time-dependent analysis, heart-lung transplantation almost halved the risk of death (relative risk, 0.57; 95% confidence interval, 0.22 to 1.48). Postoperative actuarial survival was 79% (95% confidence interval, 63% to 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

We have examined the diurnal variation in forced expiratory volume in one second (FEV1) in 25 heart-lung transplantation patients over a four week period in order to study the pathophysiological mechanisms underlying the increased mortality and morbidity which occurs at night in asthma. These patients do not have pulmonary autonomic nervous reflexes, but often have muscarinic receptor hypersensitivity. They also develop mixed cell infiltration of the lung tissue in the course of infection or rejection. Thus, they show many features in common with asthma. Seventeen patients (68%) showed a significant diurnal variation in airway calibre (mean amplitude of FEV1 was 4.6% (SD 3.7%)), which is similar to that reported in normal adults. One patient had a diurnal variation of 34.5% during an episode of rejection. This variation fell to 6.9% after steroid therapy, a change often seen in asthma. There was a correlation between increased amplitude of the variation and the presence in transbronchial biopsies of airway submucosal eosinophils and lymphocytes, associated with a histological diagnosis of acute rejection and with epithelial damage. No association was seen with muscarinic receptor sensitivity. The variation in FEV1 showed no alteration from the normal day/night synchronization, and the peak values were around 1300 h. We conclude that the diurnal variation in FEV1 after heart-lung transplantation is not dependent on autonomic nerve reflexes or muscarinic receptor sensitivity, but is related to the consequences of inflammation described above.

Quality control efforts may be biased consciously or unconsciously. External programs are handicapped by the time lapse before poor performance is disclosed. Bias induced into internal and external quality control efforts by special handling may be eliminated through submission of blind samples originating from wards, clinics, or phlebotomy areas. Evaluation of laboratory performance is obtained under conditions similar to those experienced by the patients' specimens. Calibration performance by operators, which varies considerably, can be monitored. Laboratory clerical activity can be scrutinized and errors quantitated and corrected. Perhaps most important, the sum of the effects of specimen handling and analytic variability can be determined.

Serum samples stored in a refrigerator and in ambient room air were studied for alteration of mean weight and mean concentration values. The storage period selected was four hours and the samples were variously stored exposed, refrigerated, and covered with a sample tray cover and by an airtight cover. Some storage procedures produced values more than 2 SD from the mean for many analytes. These findings were confirmed by a parallel study revealing a decrease of sample weight after the four-hour storage period. Storage at 4 C in sample cups covered by an airtight opaque shield alleviated the problem. Failure to treat external quality control sample pools in the same way as other samples will produce unexplained out-of-control results.