Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency

Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated natural killer (NK) subsets. Recent studies have shown that aberrant chemokine receptor expression on certain immune cells underlies the pathogenesis of clinical conditions in which recruitment of such cells is altered. Progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granulomatous lesions in the respiratory tract and the skin, has been described in a number of patients with transporter associated with antigen processing 2 (TAP-2) deficiency in the later stages of disease. Therefore, the goal of the present study was to elucidate whether the dysregulation of chemoattracting receptor expression on NK cells could explain abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic comparison, followed by verification with flow cytometry, revealed that chronically activated NK cells derived from 3 newly identified patients with TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR2 pathway in aberrant NK-cell retention at chronic inflammatory sites.     

Reduced 3H-imipramine binding but unaltered 3H-serotonin uptake in platelets of adolescent enuretics

High affinity 3H-imipramine binding and 3H-serotonin uptake to platelets was evaluated in nine untreated adolescent enuretics (ages 13-18) and nine age- and sex-matched controls. A significant decrease in the maximal binding of 3H-imipramine (Bmax) was observed in the enuretics as compared to the controls. No alteration in the affinity of 3H-imipramine to its binding sites (Kd) or in serotonin uptake kinetic parameters (Vmax, Km) was detected. The lack of correlation between Bmax and Vmax values might indicate that the binding sites for imipramine and the sites for serotonin uptake are not identical.     

Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia

The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re‐evaluated the FCM‐MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine‐based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background‐reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity.     

Intestinal protein loss in acute and persistent diarrhea of early childhood

GOALS: To determine fecal protein loss in children with acute and persistent diarrhea. BACKGROUND: In children with diarrhea, ongoing losses of endogenous proteins have been suggested as contributing to impairment of nutritional and immunologic status. However, there is a paucity of information and inconclusive data in the literature. STUDY: Fecal protein loss was assessed prospectively in children (<3 years of age) with acute diarrhea (<7 days' duration) or persistent diarrhea (>14 days) and in controls using alpha-1-antitrypsin determination; fecal protein loss then was correlated with age, duration of diarrhea, nutritional status, plasma proteins, and stool pathogens. RESULTS: Children with acute diarrhea (n = 43) and those with persistent diarrhea (n = 41) had significantly higher fecal alpha-1-antitrypsin levels compared with controls (n = 14) (2.26 +/- 1.71 and 2.25 +/- 1.51, respectively, vs. 1.02 +/- 0.73 mg/g stools; p = 0.002). However, there was no significant decrease of plasma albumin, globulin, or immunoglobulins. Fecal protein loss did not differ significantly among stool pathogens (bacterial, viral, and parasitic) and demonstrated no significant correlation with age, duration of diarrhea, or nutritional status (mild malnutrition). CONCLUSIONS: Enhanced fecal protein loss was observed in more than 50% of children with acute and persistent diarrhea caused by various pathogens. This did not correlate with age, duration of diarrhea, or nutritional status and did not result in significant decrease of plasma proteins or immunoglobulins. This protein-losing enteropathy does not appear to have a causal role in perpetuation of diarrheal episodes in children with mild malnutrition.     

True conversive hallucinations

A case of true conversive hallucinations in a 19-year-old female soldier is described. This phenomenon is rare and should be distinguished from psychotic or dissociative states.     

Lack of effect of 28 days of neuroleptic treatment on platelet benzodiazepine binding sites in schizophrenics

Twenty-eight days of neuroleptic treatment of 11 schizophrenics aged 16-23 years did not affect the binding values of 3H-PK 11195 to platelets. This lack of effect was in contrast to reduced peripheral benzodiazepine binding sites (PBS) observed in platelets of schizophrenics medicated over 2 years. These results may indicate that neuroleptic-induced down-regulation of PBS is a time-dependent phenomenon.     

Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial.

BACKGROUND: Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism. METHODS: In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat. RESULTS: Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia. CONCLUSIONS: The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices.     

Effects of climate on admission rates of schizophrenia patients to psychiatric hospitals.

Data on admissions of schizophrenia- and schizoaffective disorder patients to Tel-Aviv's seven public psychiatric hospitals during 11 consecutive years were obtained along with relevant meteorological information. Mean monthly admission rates were significantly higher during the summer (for schizophrenia patients) and fall (for schizoaffective patients). Schizophrenia patients' mean monthly admission rates correlated with mean maximal monthly environmental temperature (R = 0.35, N = 132 months, P <0.001). The present study may indicate that persistent high environmental temperature may be a contributing factor for psychotic exacerbation in schizophrenia patients and their consequent admission to mental hospitals.     

Decreased platelet vesicular monoamine transporter density in habitual smokers.

The brain vesicular monoamine transporter (VMAT2) is part of the re-uptake mechanism which regulates monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Nicotine induced increase of dopamine and serotonin neurotransmission in limbic structures may alter the expression of VMAT2 in brains of smokers. In this study we measured the VMAT2 pharmacodynamic characteristics using high-affinity [3H]dihydrotetrabenazine (TBZOH) binding to platelets of smokers (n=15) compared to sex and age matched healthy nonsmokers controls (n=14). A significant decrease (17%, P=0.02) in VMAT2 density (Bmax) was observed in platelets of smokers compared to nonsmokers. There was no significant difference in the affinity of [3H]TBZOH to its platelet binding site and the VMAT2 density did not correlate with the heaviness of smoking. The decreased density of the VMAT2 in the platelets of smokers may reflect nicotine induced desensitization of VMAT2, a phenomenon that may be relevant to the addictive properties of nicotine.