Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family

The RFP-TM protein family was first described in Caenorhabditis elegans as hypothetical transmembrane proteins containing a conserved 350-400 amino acid domain including the invariant peptide motif RFP. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal RFP-TM domain implying important functional properties. Here, we have identified three novel VMD2-related human genes (VMD2L1, VMD2L2 and VMD2L3) demonstrating a high degree of conservation in their respective RFP-TM domains. Each of the VMD2-like proteins has a unique C-terminus that lack similarity to other proteins or motifs. By FISH analysis, VMD2L1 was localised to chromosome 19p13.2-p13.12, VMD2L2 to 1p32.3-p33 and VMD2L3 to 12q14.2-q15. RT-PCR analyses revealed tissue-restricted expression of the three genes with both VMD2L1 and VMD2L2 abundantly transcribed in colon. VMD2L1 is present in the retinal pigment epithelium while VMD2L3 shows predominant expression in skeletal muscle.     

Reorganization of human cortical maps caused by inherited photoreceptor abnormalities

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization.     

Untersuchungen zur Methodik der Aktivitätsbestimmung der Kreatinphosphokinase

Zusammenfassung Es wurden eingehende Untersuchungen über die Methodik der Aktivitätsbestimmung der Kreatin-Phosphokinase mit Hilfe von reiner Kreatinphosphokinase und kreatinphosphokinase-haltigem Serum durchgeführt. Neben der Aktivitätsbestimmung über das in einer bestimmten Zeit aus Kreatinphosphat gebildete Kreatin wird vor allem die Bestimmung mit Hilfe des erstmals vonTanzer u.Gilvarg angegebenen DPNH-verbrauchenden optischen Testes empfohlen. Die Abhängigkeit der Reaktionsgeschwindigkeit im optischen Test von verschiedenen Faktoren wie Temperatur, ATP-, Magnesium-und Kreatinkonzentration und Anwesenheit von reduziertem Glutathion wurde geprüft und ein zur Bestimmung der Kreatin-Phosphokinase-Aktivität im Serum geeigneter Testansatz angegeben.Abkürzungen KPK Kreatinphosphokinase - HK Hexokinase - G-6-PDH Glucose-6-Phosphat-Dehydrogenase - PK Pyruvatkinase - LDH Lactatdehydrogenase - ATP Adenosintriphosphat - ADP Adenosindiphosphat - AMP Adenosinmonophosphat - PEP Phosphoenolpyruvat - GSH reduziertes Glutathion - DPN oxydiertes Diphosphopyridinnucleotid - DPNH reduziertes Diphosphopyridinnucleotid - TPN oxydiertes Triphosphopyridinnucleotid - TPNH reduziertes Triphosphopyridinnucleotid - TRAP Triäthanolamin-Hydrochlorid-NaOH-Puffer - TRIS Tris(hydroxymethyl)-amino-methan-HCl Puffer - EDTA Äthylendiaminotetraessigsäure, di-Na-Salz     

Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter

In contrast to T cells, information on skin-homing B cells expressing the cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was investigated among circulating immunoglobulin-secreting cells (ISC) and among antigen-specific antibody-secreting cells (ASC) elicited by parenteral, oral or rectal primary immunization, or by parenteral or oral secondary immunization with Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting with an enzyme-linked immunospot assay. Among all ISC, the proportion of CLA(+) cells was 13-21%. Parenteral immunization induced antigen-specific ASC of which 13% were CLA(+), while oral and rectal immunizations were followed by only 1% of CLA(+) ASC (p<0.001). Oral re-immunization was followed by an up-regulation of CLA (34-48%) regardless of the route of priming. Parenteral re-immunization elicited ASC of which 9-14% were CLA(+). In conclusion, the expression of CLA on human effector B cells depends on the site of antigen encounter: intestinal stimulation elicits cells with no CLA, while parenteral encounter elicits significant numbers of CLA(+) cells. Even though primary antigen encounter in the intestine failed to stimulate CLA expression, up-regulation of CLA was found upon intestinal antigen re-encounter. These findings may be of relevance in the pathogenesis of some cutaneous disorders.     

Immunity and depression: Insomnia,Retardation, and reduction of natural killer cell activity

Depressed patients show a reduction of natural killer (NK) cell activity which may be associated with specific depressive symptoms. The present study demonstrated that sleep disturbance and retardation, but not other depressive symptoms, were negatively correlated with NK activity in 38 depressed patients. Specific behavioral changes in depression such as sleep disturbance and retardation were found to predict 16% of the variance of cytotoxicity levels in depression.     

Genomic screen for loci associated with alcohol dependence in Mission Indians.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.     

Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria.

Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD.     

Designing immunotoxins for cancer therapy

Immunotoxins are the rapeutic agents with a high degree of specificity and unique mechanism of action. An immunotoxin is achimeric protein consisting of a targeting moiety linked to a toxin. The targeting moiety selectively binds to a tumor cell and targets it for death via the attached toxin. Generally, immunotoxins are specifically potent against cancer cells in vitro and in animal models of human malignancies. However, immunotoxins can be limited clinically by immunogenicity, toxicity, and instability. In this review, weofferwaysto overcome these limitations to create “ideal immunotoxins” for cancer therapy. These include producing single chain targeting/toxin fusion proteins of fully human origin that are extracellularly stable but once internalized, can be cleaved by intracellular proteases to free the toxin and facilitate its translocation to the cytosol.     

The utility of measures of child and adolescent anxiety: a meta-analytic review of the Revised Children's Manifest Anxiety Scale, the State-Trait Anxiety Inventory for Children, and the Child Behavior Checklist.

We evaluated the ability of the Revised Children's Manifest Anxiety Scale (RCMAS), the State-Trait Anxiety Inventory for Children (STAIC), and the Child Behavior Checklist (CBCL) to (a) discriminate between youth with an anxiety disorder and youth without a disorder, (b) discriminate between youth with an anxiety disorder and youth with either externalizing disorders or affective disorders, and (c) measure treatment change. In addition, variables, including age and sex, were explored as possible moderators of instrument utility. A meta-analysis of 43 articles was conducted. A large effect size was found when the instruments were used to compare youth with an anxiety disorder to youth without a disorder. When comparing anxious youth to psychiatric control groups, the picture was mixed; the instruments were found to be useful when discriminating between youth with an anxiety disorder and youth with an externalizing disorder, but not between youth with an anxiety disorder and children and adolescents with an affective disorder. The RCMAS, STAIC, and CBCL were found to be moderately sensitive to treatment gains.