Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma

The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.     

Disruption and basic phenotypic analysis of six novel genes from the left arm of chromosome XIV of Saccharomyces cerevisiae

We describe here the construction of six deletion mutants and their basic phenotypic analysis in three different backgrounds. The six genes were disrupted in three diploid strains (FY1679, W303 and CEN.PK2) by the long flanking homology (LFH) method (Wach, 1996). Transformants were selected as geneticin (G418)-resistant colonies and correct integration of the kanMX4 cassette was checked by colony PCR. Following sporulation of the heterozygous diploids, tetrads were dissected and scored for segregation of G418-resistance and auxotrophic markers. One of the six ORFs (YNL158w) corresponds to an essential gene which has no homology with other genes present in the databases and has two predicted transmembrane domains. Growth tests performed on different media at 15 degrees C, 30 degrees C or 37 degrees C with haploid deletants of the five non-essential genes revealed no apparent phenotype in any of them.     

Evaluation of the efficacy of naltrexone in alcoholism by the determination of serum carbohydrate-deficient transferrin

Naltrexone (NTX) has been shown to be a useful drug for the treatment of alcohol dependence (AD). Carbohydrate-deficient transferrin (CDT) in serum is a new biologic marker of alcohol abuse. To evaluate the efficacy of NTX (50 mg/d) in AD, a group of 20 alcoholics with CDT > 20 U/l was studied using monthly laboratory tests (CDT, ESR, AST, ALT, GGT) and specific psychological testing (CAGE). After the second month statistically significant differences in CDT levels were found. By the end of the study, 13 patients (responders) had normalized their CDT levels. There was no correlation between CDT values and the other laboratory markers. The difference in routine laboratory markers between responders and non responders was not significant. NTX was well tolerated by all the patients and significant alcohol abstinence was achieved. CDT was demonstrated to be a effective marker for the evaluation of alcoholic abstinence during treatment with NTX. Superior results were obtained in comparison with the routine customary markers for AD.     

Allergy to Anisakis simplex. Report of 2 cases and review of the literature

The metabolism of estradiol was investigated in postmenopausal women after 4 weeks' treatment with oral or transdermal unopposed estradiol. The urinary excretion of the metabolites was examined. With both administration routes, 2-hydroxyestrone, the main A-ring metabolite, and 16alpha-hydroxyestrone, the main D-ring metabolite, were excreted in higher amounts than estradiol and estrone. The ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone remained the same for both administration routes. It has been suggested that dominance of D-ring metabolism, i.e. increase of 16alpha-hydroxyestrone production, is associated with an increased risk of breast cancer. The present study indicates that neither oral nor transdermal estradiol substitution shift this ratio to a higher level of possible risk. Oral estradiol substitution, however, in our study leads to higher metabolite concentrations which may be regarded as hazardous for women with diseases favoring D-ring metabolism.     

XI. Yeast sequencing reports. The complete sequence of an 18,002 bp segment of Saccharomyces cerevisiae chromosome XI contains the HBS1, MRP-L20 and PRP16 genes,and six new open reading frames

We report the sequence of an 18,002 bp DNA fragment from the right arm of Saccharomyces cerevisiae chromosome XI. This segment contains nine complete open reading frames (ORFs), YKR401 to YKR409, and part of another ORF, YKR400, covering altogether 87·2% of the entire sequence. One of them, YKR400, encodes an NAD-dependent 5,10-methylene-tetrahydrofolate dehydrogenase. YKR404, YKR405 and YKR406 correspond to the previously characterized HBS1, MRP-L20 and PRP16 genes, coding for a translation elongation factor, a mitochondrial ribosomal protein and an ATP-binding protein, respectively. The putative product of YKR407 contains the zinc-binding region signature of neutral zinc metallopeptidases. The five other ORFs do not show significant homology to any known protein. The sequence data reported here have been assigned EMBL accession number Z27116.     

Transient hemifacial spasm associated with subarachnoid brainstem cysticercosis: a case report

The vestibulo-ocular reflex (VOR) and angular displacement perception were measured in 25 healthy humans in darkness before and after exposure to incoherent visual-vestibular stimulation (VVS): 45 min of repeated passive 180 degrees whole-body rotations around the vertical axis concurrent with only 90 degrees rotation in a visual virtual square room. Large inter-individual variability was observed for both VOR gain and turning estimates. The individual VOR gains were not correlated with perceived angles of rotation either before or after VVS. After VVS, the angular displacement perception decreased by 24+/-16% while the VOR gain did not change significantly. The results suggest that adaptive plasticity in turning perception and adaptive plasticity in VOR might be independent of one another.     

Pre-postoperative neuropsychological evaluation in the surgical treatment of epilepsy

INTRODUCTION: Epilepsy is one of the most common neurological disorders, affecting about one percent of the world population. Pharmacological treatment fails in one-third of these patients. Surgical intervention has become an accepted treatment option for those patients with seizure disorders that are refractory to conventional therapies. Cortical resection and callosotomy are the most widely accepted methods of surgical intervention. A prerequisite for success in this type of surgical intervention is the preoperative clinical assessment of the epilepsy surgery candidate. DEVELOPMENT: This paper examines the current uses of neuropsychological assessment in an epilepsy surgery program. Several areas are addressed for discussion with respect to the contributions of neuropsychological assessment: the preoperative evaluation of the epilepsy surgery candidates, including the clinical examination of language and memory functions during the Wada test; the neuropsychological changes that result from surgery and the predictive role of neuropsychology in these areas, and prediction for seizure control following surgery. CONCLUSION: Assessment of cognitive functions is an important component of the preoperative evaluation of the epilepsy surgery candidate, and is needed in order to obtain complete diagnostic information.     

Automatic parameter tuning for functional regionalization methods

The methods used to define functional regions for public statistics and policy purposes need to establish several parameter values. This is typically achieved using expert knowledge based on qualitative judgements and lengthy consultations with local stakeholders. We propose to support this process by using an optimization algorithm to calibrate any regionalization method by identifying the parameter values that produce the best regionalization for a given quantitative indicator. The approach is exemplified by using a grid search and a genetic algorithm to configure the official methods employed in the UK and Sweden for the definition of their respective official concepts of local labour markets.     

Analysis of 41 kb of the DNA sequence from the right arm of chromosome II of Schizosaccharomyces pombe

We report the complete sequence of cosmid c18A7 (41 046 bp insert), located on the right arm of chromosome II of the Schizosaccharomyces pombe genome. The sequence, which partially overlaps with cosmids SPBC4F6 and SPBC336, contains 16 open reading frames (ORFs) capable of coding for proteins of at least 100 amino acid residues in length (one partial) and one small nucleolar RNA (snoRNA). Four known genes were found: swi10 (encoding a mating-type switching protein also involved in nucleotide excision repair); dim1 (encoding a dimethyladenosine transferase); arf1 (encoding ADP-ribosylation factor 1); and pol3 (cdc6) the partial fragment, encoding the 125 kDa catalytic subunit of the DNA polymerase type B. Six ORFs similar to known proteins were found. They include a transporter of the major facilitator superfamily class, a vacuolar sorting protein, an asparagine synthase, a nuclear protein, a reticulum oxidoreductin and a heat shock protein. Each protein product of the other six ORFs has conserved domains and can be assigned a molecular, but not a biological, function. The sequence has been submitted to the EMBL database under Accession No. AL080287.     

DNA sequencing and analysis of a 40 kb region from the right arm of chromosome II from Schizosaccharomyces pombe

We have determined the complete nucleotide sequence of a 39,648 bp segment, contained in cosmid c32F12, derived from the right arm of chromosome II from the fission yeast Schizosaccharomyces pombe. Computer analysis of the sequence revealed the presence of 15 non-overlapping open reading-frames (ORFs) longer than 300 bp and one tRNA-Thr gene. Six ORFs correspond to the previously known rec14+, tug1+, rum1+, pch1+, gpd1+ and cyr1+ genes. Five ORFs code for putative proteins with significant homology to proteins from other organisms. SPBC32F12.01c shows considerable similarity to human neutral sphingomyelinase, whereas SPBC32F12.03c, SPBC32F12.10 and SPBC32F12.14 exhibit strong homology to glutathione peroxidase, phosphoglucomutase and ubiquitin protein ligase E-3 components from various organisms, respectively. The four remaining ORFs identified show weak or non-significant homology to previously sequenced genes. The nucleotide sequence has been submitted to the EMBL database under Accession Number AL023796.