AID from bony fish catalyzes class switch recombination

Class switch recombination was the last of the lymphocyte-specific DNA modification reactions to appear in the evolution of the adaptive immune system. It is absent in cartilaginous and bony fish, and it is common to all tetrapods. Class switching is initiated by activation-induced cytidine deaminase (AID), an enzyme expressed in cartilaginous and bony fish that is also required for somatic hypermutation. Fish AID differs from orthologs found in tetrapods in several respects, including its catalytic domain and carboxy-terminal region, both of which are essential for the switching reaction. To determine whether evolution of class switch recombination required alterations in AID, we assayed AID from Japanese puffer and zebra fish for class-switching activity in mouse B cells. We find that fish AID catalyzes class switch recombination in mammalian B cells. Thus, AID had the potential to catalyze this reaction before the teleost and tetrapod lineages diverged, suggesting that the later appearance of a class-switching reaction was dependent on the evolution of switch regions and multiple constant regions in the IgH locus.     

Prenatal diagnosis for arginase deficiency by second-trimester fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis

Hyperargininemia is a progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. We diagnosed arginase deficiency in a three-year-old male child of first-cousin Palestinian Arab parents. Prenatal diagnosis of an unaffected fetus was achieved in the second trimester of a subsequent pregnancy by cordocentesis and analysis of arginase activity in fetal erythrocytes. ARG1 mutation analysis in the proband revealed homozygosity for a deletion of 10,753 bp extending from the first intron to beyond the poly (A) site of the gene. This is the first gross deletion in the ARG1 gene to be identified and the first mutation to be described in an arginase-deficient patient of this ethnic origin. The identification of the ARG1 deletion in this family enabled first-trimester prenatal diagnosis in a subsequent pregnancy by multiplex PCR analysis performed on chorionic villous DNA.     

Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder

OBJECTIVE: Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder. The authors studied a specific omega-3 fatty acid, the ethyl ester of eicosapentaenoic acid (E-EPA), as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy. METHOD: Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week, parallel-group, double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy. Seventeen of the patients were women, and three were men. RESULTS: Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment. CONCLUSIONS: It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own.     

A randomized study of intracytoplasmic sperm injection (ICSI) versus subzonal insemination (SUZI) for the management of severe male-factor infertility

Objective Our objective was to compare the fertilization rates achieved by ICSI versus SUZI in couples with severe male infertility.Design This was a randomized, prospective study.Setting The study took place at the In-Vitro Fertilization-Embryo Transfer Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center.Materials and Methods Oocytes of 12 patients were randomly allocated to either ICSI or SUZI procedures. Each woman thus served as her own control. All 12 patients had undergone at least two previous in vitro fertilization cycles with no fertilization or had a very low sperm count, i.e., a total motile sperm count of less than 0.5 × 10 ⁶.Results A total of 117 oocytes was obtained for fertilization. Of these oocytes, 16% (10/63) were successfully fertilized by SUZI, compared to 33% (18/54) treated by ICSI. This difference was statistically significant (P < 0.05). Of the 12 cycles, ICSI provided embryos in 10 cycles (83%), while SUZI was successful in only 6 cycles (50%). Four pregnancies were achieved: 33% per attempt, or 40% per transfer.     

Impact of in-patient research participation on subsequent heroin use patterns: implications for ethics and public health

Aims Research on drug dependence often involves the administration of drugs of abuse to experienced drug users under controlled laboratory conditions. The primary objective of this study was to assess whether participation in such research alters the frequency of heroin use by non‐treatment‐seeking opioid‐dependent volunteers after study completion. Design Data were examined from four in‐patient studies involving controlled opioid administration. Setting Substance Use Research Center at Columbia University, New York State Psychiatric Institute. Participants Sixty‐nine heroin‐dependent volunteers. Measurements Participants' self‐reported heroin use prior to and 1 month after study participation was compared using a Wilcoxon test. Because a number of participants reported that they had stopped using heroin, a logistic regression was used to identify correlates of heroin cessation 1 month after study completion. Findings One hundred and one participants entered laboratory studies and 69 completed them. Self‐reported heroin use significantly decreased 1 month after study participation [1.7 (±2.0) bags per day] compared to baseline [6.8 (±4.2) bags per day], P < 0.001 among the 69 completers. In addition, 42% of the completers were heroin‐abstinent 1 month after study completion. Being African American, having a history of opioid dependence treatment, reporting heavier heroin use at baseline and a longer history of heroin use were correlated with cessation of heroin use. Conclusions Participation in opioid administration studies does not increase subsequent heroin use and for some individuals leads to accessing opioid dependence treatment and cessation of heroin use in the short term.     

Female Runner With Painful Left Thigh Swelling: A Case of May-Thurner Syndrome

We discuss a case of a female runner who presented with burning left groin and thigh pain and positional swelling after a long run. The workup revealed May-Thurner syndrome. May-Thurner syndrome anatomy is a common anatomical variant present in approximately 20% of the population. Compression of the iliac vein may result in venous stasis in the lower limb with a predisposition to deep venous thrombosis. We identify 4 reported cases of May-Thurner syndrome in female runners and review the importance of diagnosis and appropriate treatment of this condition.

Morphine deprivation increases self-administration of the fast- and short-acting mu-opioid receptor agonist remifentanil in the rat

Opiate dependence and withdrawal have long been hypothesized to enhance the reinforcing effects of opiates; however, opiate agonist self-administration in these states has yet to be systematically assessed. To address this issue, the reinforcing property of the short-acting mu-opioid agonist, remifentanil, was assessed in morphine-dependent (MD), morphine-dependent and -withdrawn (MW), and nondependent, control (C) rats. Dependence was established by twice daily administration of increasing doses of morphine for 4 days (10, 20, 30, and 40 mg/kg s.c.) and then maintained with a daily injection of the large dose. Morphine deprivation-induced withdrawal (defined by weight loss and hyperalgesia) was apparent 24, but not 12, h after morphine treatment. Remifentanil self-administration (0.4, 0.8, 1.6, 3.2, or 6.4 mug/kg/infusion) was assessed over 20 successive, daily, 1-h sessions, either 12 or 24 h after the maintenance dose of morphine. Compared with the control group, the MD group demonstrated suppressed remifentanil self-administration, whereas the MW group exhibited enhanced responding for every dose of remifentanil. The increased responding observed in the MW group compared with the control and MD groups resulted in an upward shift in the remifentanil dose-response curve, an effect that was expressed only after repeated exposure to the contingency, demonstrating that morphine withdrawal ultimately enhances the reinforcing effects of remifentanil.     

Microcirculation response to local cooling in patients with Huntington’s disease

Altered autonomic nervous system (ANS) functioning in early stages of Huntington's disease (HD) has been suggested, presumably due to distorted high-order autonomic control. ANS functioning in the early stages of HD was further investigated. Laser-Doppler (LD) flux in the skin of the fingertips, heart rate (HR), HR variability, systolic and diastolic blood pressure were measured during rest and during a 6 min cooling of one hand at 15°C. Data of 15 presymptomatic gene mutation carriers (PHD), 15 early symptomatic HD patients (EHD), and two groups of 15 age- and sex-matched controls were compared. The area under the low frequency (LF) and high frequency (HF) bands of the HR variability spectrum were calculated. An augmented reduction of cutaneous LD flux was found in response to the direct cooling in the PHD group (37.5 ± 8.5% of resting value) compared to the PHD controls (67.27 ± 8.4%) (p < 0.05). In addition, the PHD group had higher (LF/(LF + HF) index of primary sympathetic modulation of the HR at rest (53.6 ± 3.3) compared to the EHD patients (39.7 ± 4.2) (p < 0.05). In the EHD group, a significantly smaller change of HR during cooling (100.26 ± 1.2%) was found compared to the EHD controls (95.9 ± 1.0%) (p < 0.05). The results are in line with the hypothesis that ANS dysfunction occurs even in PHD subjects. Further, they support the hypothesis that dysfunction of the high-order autonomic centres are involved in HD.