Peripheral Thy1+ lymphocytes rearranging TCR‐γδ genes in LAT‐deficient mice

Linker for activation of T cells (LAT) is an adaptor molecule indispensable for development of αβ and γδ T lymphocytes. Surprisingly, using a new model of LAT‐deficient mice we found that despite arrested thymic development, a discrete population of cells with active Lat promoter, expressing Thy1 molecules, accumulated in peripheral lymphoid organs of homozygous (Lat^Inv/Inv) mutant mice. By measuring frequencies of TCR gene rearrangements in conjunction with a panel of cell surface Ag, we dissected two subsets of these Thy1⁺ cells. Thy1^dull cells expressed markers of NK lymphocytes and contained low frequency of TCR‐γ gene rearrangements without detectable TCR‐δ rearrangements. Thy1^high cells resembled immature CD44⁺CD25⁺ thymocytes and contained high frequency of non‐productive TCR‐γ and TCR‐δ rearrangements, indicating that cells displaying molecular signatures of commitment toward γδ T‐cell lineage can develop and populate lymphoid tissues of LAT‐deficient mice. Phenotypically similar Thy1^high cells were also found in lymph nodes of lymphocyte‐deficient (Rag2^?/?) mice but not in T lymphocyte proficient, heterozygous Lat^+/Inv mice suggesting that Thy1^high cells of LAT‐deficient mice identified in this study accumulate in peripheral lymphoid organs as a result of congenital lymphopenia.     

Role of the region 23-28 in Abeta fibril formation: insights from simulations of the monomers and dimers of Alzheimer's peptides Abeta40 and Abeta42

Self-assembly of the 40/42 amino acid Abeta peptide is a key player in Alzheimer's disease. Abeta40 is the most prevalent species, while Abeta42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Abeta monomer and a bent in this region could be the rate-limiting step in Abeta fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Abeta(21-30) and the monomers Abeta40 and Abeta42. On the basis of new simulations on dimers of full-length Abeta, we propose that the rate-limiting step involves the formation of a multimeric beta-sheet spanning the central hydrophobic core (residues 17-21).     

Pain perception in schizophrenia: no changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization

BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both excitatory (e.g. sensitization) and inhibitory endogenous modulation systems. Preliminary experimental studies have shown diminished pain sensitivity in schizophrenia patients. The objective of the study was to investigate the role of excitatory and inhibitory systems on pain perception in schizophrenia. METHODS: Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity. Excitatory and inhibitory systems were elicited using a temporal summation test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time was a significant predictor of pain scores in controls, but not in patients. That is, pain ratings increased during the tonic thermal stimulation among controls but not in schizophrenia patients. When correlation coefficients (between time and pain ratings) for patients and controls were compared, the correlation coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04; p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar in magnitude in both patients and controls. CONCLUSIONS: Diminished pain sensitivity in schizophrenia may be related to abnormal excitatory mechanisms, but not to DNIC. More studies are needed to better characterize the neurophysiological and neurochemical mechanisms involved in the lack of sensitization in schizophrenia.     

Acute acquired toxoplasmosis presenting as polymyositis and chorioretinitis in immunocompetent patient

The parasite Toxoplasma gondii mainly encysts in brain, retina, myocardium, and skeletal muscle. It has been implicated in the genesis of inflammatory myopathies for years, but the parasite usually cannot be detected in the muscle. It is established, however, that toxoplasmosis can cause myositis either by recent infection or by reactivation. The case of a non-HIV patient who developed an acute polymyositis upon infection by T. gondii is reported. We suggest that all patients with polymyositis should have serological tests for toxoplasmosis as a part of their initial evaluation and early trial of antiprotozoal therapy in case of positive findings.     

Karyotyping,Is It Worthwhile in Transsexualism?

IntroductionKaryotyping is often performed in transsexual individuals.AimQuantification and characterization of karyotype findings and abnormalities in transsexual persons.Main Outcome MeasuresKaryotypes were listed both in male‐to‐female and in female‐to‐male transsexual persons.MethodsThe data were collected through a retrospective study.ResultsKaryotypes of 368 transsexual individuals (251 male‐to‐female, 117 female‐to‐male) are described. Normal findings were found in 97.55%. Prevalence of abnormal karyotypes was 3.19% among male‐to‐female, and 0.85% among female‐to‐male transsexuals. Nine karyotypes showed variations; Klinefelter syndrome was confirmed in three persons, whereas others displayed autosomal aberrations.ConclusionKaryotyping is only of very limited information in the transsexual population. Inoubli A, De Cuypere G, Rubens R, Heylens G, Elaut E, Van Caenegem E, Menten B, and T'Sjoen G. Karyotyping, is it worthwhile in transsexualism?     

MRI Findings Do not Correlate with Outcome in Athletes with Chronic Groin Pain

This trial aimed to assess the value of MRI in the differential diagnosis of chronic groin pain in athletes, a condition caused by various pathologies, the most common being posterior abdominal wall deficiency, osteitis pubis and muscular imbalance. Nineteen subjects with clinically ruled-out hernia and recurrent episodes of exercise-triggered groin pain were assessed. Dynamic MRI was performed under Valsalva manoeuver and at rest within a training- free period and after training activity. Follow-up was performed after 4 years using a questionnaire and physical examination. An incipient hernia was seen in one case, Valsalva manoeuver provoked a visible bulging in 7 others (3 bilateral). Eight athletes showed symphysitis (accompanied by bulging in 3 cases). MRI visualized one hydrocele, one osteoma of the left femur, one enchondroma of the pubic bone, and one dilated left ureter without clinical symptoms or therapeutic relevance. MRI findings after training and during the training free period did not vary. Fifteen participants were available for a follow-up control examination 4 years later - one suffered from ongoing pain, eleven were free of symptoms and three had improvement. However, most of them improved only with changing or reducing training. There were four participants with a specific therapy of their MRI findings. MRI revealed a variety of pathological findings in athletes suffering from chronic groin pain, but it was not reliable enough in differentiating between diagnoses requiring conservative or operative treatment. The MRI examination within the training interval did not have an advantage to that within the training-free period. Further randomized prospective trials with a long follow-up should establish whether MRI findings could be of help in the choice between conservative and surgical treatment for chronic groin pain.

Key points

• MRI findings after training and during the train free period did not vary.
• MRI revealed a variety of pathological findings in athletes suffering from chronic groin pain, but it was not reliable enough in differentiating between diagnoses requiring conservative or operative treatment.

Key words: MRI, hernia, athletes, chronic groin pain, symphysitis     

Analysis of Mutations in the Plasma Cholinesterase Gene of Patients with a History of Prolonged Neuromuscular Block during Anesthesia

Decreased activity of plasma cholinesterase is responsible for prolonged apnea during anesthesia using neuromuscular blockers such as suxamethonium and mivacurium. More than 20 mutations have been identified so far in the BCHE gene resulting in impaired plasma cholinesterase activity. Biochemical tests are not always able to differentiate between pathological and normal sera; hence in some cases unanticipated complications can still occur during anesthesia even after measurements of enzyme activity and dibucaine numbers within the normal range. Therefore, molecular genetic testing is required for the accurate diagnosis of this deficiency. Here we present a study of plasma cholinesterase activity and BCHE genotyping of patients with a history of prolonged neuromuscular block and most of their pedigrees. All four exons of the BCHE gene were directly sequenced from samples and a number of mutations responsible for the reduction of plasma cholinesterase activity were identified. In most cases the atypical mutation in exon 2 (nt 209A --> G, Asp70 --> Gly) was found together with the K-variant mutation in exon 4 (nt 1615G --> A, Ala539 --> Thr), which is in good agreement with previous data suggesting that these mutations along with two others (at nt -116 and nt 1914) are in linkage disequilibrium.     

Local dexamethasone therapy conserves hearing in an animal model of electrode insertion trauma-induced hearing loss.

HYPOTHESIS: The progressive loss of hearing that develops after electrode insertion trauma (EIT) can be attenuated by local dexamethasone (DXM) therapy. BACKGROUND: Hearing loss (HL) that develops after cochlear implant EIT occurs in two stages in laboratory animals, that is, an immediate loss followed by a progressive loss. Direct infusion of DXM into the guinea pig cochlea can attenuate both ototoxin- and noise-induced HL. MATERIALS AND METHODS: Auditory-evoked brainstem responses (ABRs) of guinea pigs were measured for 4 frequencies (i.e., 0.5, 1, 4, and 16 kHz) before, immediately after, and more than 30 days post-EIT for experimental (EIT,EIT + artificial perilymph, and EIT + DXM) and for the contralateral unoperated cochleae of each group. An electrode analog of 0.14-mm diameter was inserted through a basal turn cochleostomy for a depth of 3 mm and withdrawn. DXM in artificial perilymph was delivered immediately post-EIT into the scala tympani via a miniosmotic pump for 8 days. RESULTS: The ABR thresholds of EIT animals increased progressively post-EIT. Contralateral unoperated cochleae had no significant changes in ABR thresholds. Immediately post-EIT, that is, Day 0, the DXM-treated animals exhibited a significant HL at 1, 4, and 16 kHz, but this HL was no longer significant by Day 30 compared with contralateral control ears. CONCLUSION: The results from immediate local treatment of the cochlea with DXM in an animal model of EIT-induced HL suggest a novel therapeutic strategy for hearing conservation by attenuating the progressive HL that can result from the process of electrode array insertion during cochlear implantation.