Presence and measurement oftele-methylhistamine in mast cells

The histamine metabolitetele-methylhistamine (t-MH) was identified and measured in crude and purified peritoneal mast cells (MCs). Peritoneal dialysates, peritoneal cells, and purified MCs all containedt-MH in concentrations representing about 0.2% of the corresponding histamine (HA) levels.T-MH levels in crude cells represented about 70% of the total dialysate levels, indicating the presence of extracellular as well as intracellulart-MH.T-MH levels per MC in purified fractions were similar to those of crude fractions, indicating a MC origin for the intracellulart-MH. Histamine methyltransferase activity was not detected in crude or purified MC fractions, and incubations with the monoamine oxidase inhibitor pargyline failed to increase the content or release oft-MH in either fraction, suggesting a very slow or non-existent histamine methylation in MCs. Compound 48/80 produced a temperature-dependent release of HA andt-MH in crude and purified preparations, and Triton X-100 also released both amines. In all cases, the degree of release of both amines was correlated, consistent with a granular origin fort-MH in MCs. The low concentrations oft-MH in MCs do not necessarily indicate a role for MCs in HA metabolism, but suggest thatt-MH may be a valuable marker for non-MC HA.     

Partial trisomy 22: A recognizable syndrome

A patient identified as being a partial trisomy 22 mosaic is presented. The presence of a translocation t(4;22) (pter;q12) is noted in the mother, sister and maternal aunt. Comparison is made with nine other reported cases of partial trisomy 22 confirmed by parental translocation. These suggest a definite syndrome, including mental retardation, congenital heart disease, skeletal anomalies, anti-mongoloid slant of the palpebral fissures, preauricular skin tags and low-set ears.     

Antibody Responses to Group A Streptococcal Infections in the Hamster

The immune response after streptococcal infections of the skin and of the joints was studied in an experimental animal model. Hamsters were challenged intradermally or intra-articularly with different streptococcal serotypes, and antibodies for streptolysin O (ASO), deoxyribonuclease B (anti-deoxyribonuclease B), and group A carbohydrate (anti-group A CHO) were determined. After a single injection at either site, 7 of 48 animals (14%) developed group A-CHO antibodies; however, none of the animals developed detectable levels of ASO or anti-deoxyribonuclease B. After repeated infections of the skin or joint, anti-deoxyribonuclease B antibodies were detectable in 13% (4 of 30) and 30% (5 of 17) of the animals, respectively. Elevations of ASO occurred after repeated joint infections in 4 of 16 animals (25%), whereas none of 30 hamsters repeatedly infected intradermally developed antibodies against streptolysin O. For all three antibodies tested, elevated levels were more frequently noted after repeated joint infections than after repeated skin infections with the same streptococcal serotype. These data, similar to ones previously noted in human impetigo, indicate that ASO responses are feeble after streptococcal skin infections and that the site of infection per se, rather than the infecting strain, appears to be responsible for this poor response.     

The effect of 2,4-dinitrophenol and related compounds on bile secretion

1. 2,4-dinitrophenol, 2,4-dinitrophenetole, 2,4-dinitronaphthol, 4,6-dinitro-o-cresol, and to a lesser extent picric acid, produced an increase in bile flow and a rise in body temperature in the anaesthetized dog. The total biliary bromsulphalein (BSP) excretion in unit time was either slightly reduced, increased or remained at its pre-injection level.2. Picramic acid, the nitrochlorophenols and 2,4-dinitrobenzaldehyde caused a moderate increase in bile flow without an effect on the temperature of the animal.3. The three mononitrophenols, the five remaining isomeric dinitrophenols, isopicramic acid, the aminonitrophenols, phenol, 2,4-dinitroanisole, 2,4-dinitrobenzoic acid, 2,4-dinitrobenzene sulphonic acid, 2,4-dinitroresorcinol and 4-nitracatechol had little effect on bile secretion or body temperature.4. It thus appears that, in order for a compound of this type to have a pronounced effect on bile secretion, it is necessary to have nitro groups in positions 2 and 4 of the benzene ring, and a free or potential hydroxyl group.     

Microdissection genotyping of mixed glial and primitive neuroectodermal central nervous system neoplasm

A 22-year-old man with previous radiation treatment for childhood astrocytoma underwent resection of a right parietooccipital lesion. Histopathology revealed a malignant neoplasm with areas of astrocytic and primitive neuroectodermal components. To resolve the relationship and cellular origin, representative tissue was microdissected from several targets, obtaining a balanced mixture of each element. Nonneoplastic brain parenchyma was separately microdissected to determine polymorphic marker informativeness and to serve as an internal negative control. Despite the relatively small quantity of tissue removed for each microdissection target, sufficient material was available for reliable, balanced, polymerase chain reaction-format genotyping encompassing a panel of tumor suppressor genes and genetic loci associated with these forms of neoplasia. The findings revealed distinct discordant genotypic profiles for each of the neoplastic components. The efficacy of the approach used for molecular analysis of this complex neoplasm and the implication of the genotypic findings are discussed.     

The relationship between social anxiety disorder and alcohol use disorders: a critical review

Epidemiological studies have demonstrated a significant co-morbidity between social anxiety disorder (SAD) and alcohol use disorders (AUDs). Despite the fact that many studies have demonstrated strong relationships between SAD and AUD diagnoses, there has been much inconsistency in demonstrating causality or even directionality of the relationship between social anxiety and alcohol-related variables. For example, some studies have showed a positive relationship between social anxiety and alcohol-related variables, while others have shown a negative relationship or no relationship whatsoever. In an attempt to better understand the relationship between social anxiety and alcohol, some researchers have explored potential moderating variables such as gender or alcohol expectancies. The present review reports on what has been found with regard to explaining the high co-morbidity between social anxiety and alcohol problems, in both clinical and non-clinical socially anxious individuals. With a better understanding of this complex relationship, treatment programs will be able to better target specific individuals for treatment and potentially improve the efficacy of the treatments currently available for individuals with co-morbid SAD and AUD.     

Psychiatric disorders associated with risk for the development of eating disorders during adolescence and early adulthood

Longitudinal data were used to investigate whether anxiety, depressive, disruptive, personality, or substance use disorders are associated with risk for the development of eating disorders during adolescence or early adulthood. Psychiatric disorders were assessed among 726 youths from a random community sample during adolescence and early adulthood. Depressive disorders during early adolescence were associated with elevated risk for the onset of eating disorders, dietary restriction, purging behavior, and recurrent weight fluctuations after preexisting eating problems and other psychiatric disorders were controlled statistically. Disruptive and personality disorders were independently associated with elevated risk for specific eating or weight problems. The present findings suggest that depressive disorders during early adolescence may contribute to the development of eating disorders during middle adolescence or early adulthood.     

Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow

Our laboratory has characterized a population of stromal cells obtained from adipose tissue termed processed lipoaspirate cells (PLAs). PLAs, like bone-marrow derived mesenchymal stem cells (BM-MSCs), have the capacity to differentiate along the adipogenic, osteogenic, chondrogenic, and myogenic lineages, In order to better characterize these two multi-lineage populations, we examined the surface phenotype of both bone marrow and adipose tissue-derived cells from five patients undergoing surgery. PLA and BM-MSC cells were isolated, subcultivated, and evaluated for cell surface marker expression using flow cytometry. PLA and BM-MSC cells both expressed CD13, CD29, CD44, CD90, CD105, SH-3, and STRO-1. Differences in expression were noted for cell adhesion molecules CD49d (Integrin alpha4), CD54 (ICAM-1), CD34, and CD106 (VCAM-1). While markedly similar, the surface phenotypes of PLA and BM-MSC cells are distinct for several cell adhesion molecules implicated in hematopoietic stem cell homing, mobilization, and proliferation.     

Adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kDa micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx mice

Duchenne muscular dystrophy is a severe life-threatening X-linked recessive disorder, caused by mutations in the dystrophin gene, for which currently there is no effective treatment. Because of the large size of the dystrophin cDNA (14 kb) this precluded it from being used in early adenovirus- or retrovirus-based gene therapy vectors. However, some therapeutic success has been achieved in mdx mice using adenovirus- and retrovirus-mediated transfer of a 6.3 kb recombinant mini-dystrophin cDNA. Despite this, problems with immunogenicity and inefficient transduction of mature myofibres make these vectors less than ideal for gene transfer to skeletal muscle. Adeno-associated viral (AAV) vectors overcome many of the problems associated with other vector systems. However, AAV vectors can only accommodate <5 kb of foreign DNA. For this reason we have produced a micro-dystrophin cDNA gene construct that is <3.8 kb. This construct, driven by a CMV promoter, was introduced into the skeletal muscle of 12-day-old nude/mdx mice using an AAV vector, resulting in specific sarcolemmal expression of micro-dystrophin in >50% of myofibres up to 20 weeks of age, and effective restoration of the dystrophin-associated protein (DAP) complex components. Additionally, evaluation of central nucleation indicated a significant inhibition of degenerative dystrophic muscle pathology. We have therefore shown that the current micro-dystrophin gene delivered in vivo using an AAV vector is not only capable of restoring sarcolemmal DAP complexes, but can also ameliorate dystrophic pathology at the cellular level.