Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Ultrasonographic assessment of human skeletal muscle size

The measurement of human muscle size is essential when assessing the effects of training, disuse and ageing. The considered gold standard for cross-sectional area measurements of muscle size is magnetic resonance imaging (MRI). However, MRI is costly and often inaccessible. The aim of the present study was to test the reproducibility and validity of a more accessible alternative method using ultrasonography (ULT). We examined the cross-sectional areas in the vastus lateralis muscle of six individuals. Axial-plane ULT scans were taken at given levels along the entire muscle length. The ULT scanning was repeated on different days (reliability) and validated against MRI-based measurements. Mean intraclass correlation coefficients were 0.998 for the reliability of ULT and 0.999 for the validity of ULT against MRI. The coefficient of variation values for cross-sectional area measurements assessed by six different experimenters were 2.1% and 0.8% for images obtained with ULT and MRI, respectively. The ULT method is a valid and reliable alternative tool for assessing cross-sectional areas of large individual human muscles. The present findings justify the application of the ULT method for the detection of changes throughout large muscles in response to training, disuse or as a consequence of sarcopenia.     

Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region

The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex.     

Expansion of CTG repeat in myotonin protein kinase gene on Alu(ins)-HinfI-I background in a myotonic dystrophy patient from India. Mutations in brief no. 210. Online

To determine the founder of Indian myotonic dystrophy mutation, we have studied the expansion of CTG repeats in myotonin protein kinase gene and two intragenic linked loci Alu(ins) / Alu(del) and G/T intron 9 HinfI polymorphism in ten unrelated DM patients from eastern India. Out of these ten patients, reconstruction of haplotype was possible for five patients unambiguously. In the other five cases, haplotype for the normal allele was assumed to be the most common haplotype found in normal individuals from Indian populations. Such analysis showed that in nine cases, the expansion of CTG repeats took place on Alu(ins)-HinfI-2 background indicating common founder with other DM mutation published. However, in one case we observed a different haplotype [Alu(ins)-HinfI-1] which could be a new mutation or due to admixture.     

Viral hemagglutinin augments peptide-specific cytotoxic T cell responses

In attempt to increase the induction of peptide-specific cytolytic T cells (CTL) we investigated the effect of the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) gene product on the activation of peptide-specific CTL. Spleen cells of CH3 mice immunized against the influenza nucleoprotein peptide 50–63 (NP 50–63) were restimulated in vitro (i) with peptide-pulsed syngeneic fibroblast cells (Ltk^?) as antigen-presenting cells, which were in addition (ii) infected with NDV or (iii) stably transfected with the HN cDN A of NDV. A greater than sixfold increase in peptide-specific CTL responses was observed in cultures restimulated with peptide-pulsed Ltk^? cells which co-expressed viral hemagglutinin due to either infection or transfection. A similar augmentation was seen in CTL responses against other types of antigen (major histocompatibility complex alloantigens, minor histocompatibility antigens or tumor antigens) when suboptimal cultures were stimulated with the respective antigen-presenting cells modified by NDV infection. These findings suggest that NDV or viral HN expressed on antigen-presenting cells or tumor cells can exert a T cell co-stimulatory function.     

Phenotypic characterization of regulatory CD4+CD25+ T cells in rats

CD25 has become widely used as a marker for a subset of regulatory CD4(+) T cells present in the thymus and periphery of mice, rats and humans. However, CD25 is also expressed on conventionally activated T cells that are not regulatory and not all peripheral regulatory T cells express CD25. The identification of a stable and unique marker for regulatory T cells would therefore be valuable. This study provides a detailed account of the phenotype of CD4(+)CD25(+) regulatory T cells in rats. In the thymus, CD4(+)CD8(-)CD25(+) cells were found to have a more mature phenotype than the corresponding CD4(+)CD8(-)CD25(-) cells with respect to expression of Thy1 (CD90), CD53 and CD44, suggesting that CD25 expression, and perhaps commitment to regulatory function, might be a late event in thymocyte development. CD4(+)CD25(+) cells in both the thymus and periphery were found to have enriched and heterogeneous expression of activation markers such as OX40 (CD134) and OX48 (an antibody determined in this study to be specific for CD86). CD4(+)CD25(+) T cells were also found to have enriched expression of CD80, at both the mRNA and protein level. However, functional studies in vitro and in vivo showed that neither OX40 or CD86 were useful markers for the further subdivision of regulatory T cells. Our studies indicate that, at present, CD25 remains the most useful marker to enrich for regulatory CD4(+) T cells in rats and no further subdivision of the regulatory component of CD4(+)CD25(-)CD45RC(low) T cells has yet been achieved.     

Thermoluminescent dosimetry of the SourceTech Medical model STM1251 125I seed

Many new models of 125I seeds are being introduced, mainly due to the increase in prostate seed implants. We have evaluated the SourceTech Medical (STM), model STM1251, 125I seed using thermoluminescent dosimeters (TLDs) in a solid water phantom. TLD cubes, LiF TLD-100, with dimension 1 mm on each edge, were irradiated at various distances, 1, 2, 3, and 5 cm, at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. Sensitivity calibration of the TLDs was achieved by irradiation to 10 cGy with 6 MV x rays from a clinical linear accelerator, Clinac 600C. Concurrent with the 125I seed exposures, several TLDs were also exposed to 10 cGy with the 600C as a control set. Dose rates per unit air kerma strength were determined based on the 1999 NIST traceable standard for the STM1251 seed. They are presented as a function of distance r and angle theta. The TG-43 parameters, including the dose rate constant, lambda, anisotropy function, F(r,theta), radial dose function, g(r), anisotropy factor, phian(r), and anisotropy constant, phi, were obtained for use in radiation treatment planning software. The value of lambda was determined as 1.07 +/- 5.5% cGy U(-1) h(-1), which is comparable to model 6702 and to the value determined using the point extrapolation method by Kirov and Williamson. We also find agreement between our TLD data and their Monte Carlo results for g(r), F(r,theta), phian(r), and phi. Additionally, agreement is found with the TLD data of Li and Williamson for lambda and g(r).     

Plasma metabolites after 2-deoxy-D-glucose in rats with brain dopamine-depleting lesions

Rats with selective brain dopamine-depleting lesions produced by 6-hydroxydopamine failed to increase their food intake after 2-deoxy-D-glucose administration. Their hyperglycemic response to 2DG was identical to that of intact controls. Neither group showed significant mobilization of free fatty acids or production of ketones.     

Quinine drinking: More regulatory puzzles

Rats were permanently hypodipsic when offered a quinine adulterated fluid on a chronic basis. Plasma osmolarity and Na concentration were normal, but the quinine drinkers showed a slight hyperkalemia compared to water drinking controls. The quinine-drinking rats maintained hydromineral equilibrium through the excretion of a small amount of concentrated urine. The quinine intake was closely matched to need, and fell to near zero when food was removed or water was supplied intravenously. This harmony of intake and output was disrupted after acute hypertonic NaCl load: while the obligatory salt diuresis was no different between water and quinine drinkers, the latter did not drink (except at the lowest level of adulteration) within several hours. However, by 24 hr all had shown a delayed drinking response. This delay in drinking of quinine was also evident after non-painful intravenous NaCl infusions, but no drinking occurred after nephrectomy. Quinine drinkers were also unresponsive to isoproterenol and intracranial dipsogens. These data are discussed in terms of their implication for definitions of regulatory drinking behavior.