Depressive Symptoms Among HIV Positive Men: Life Stress,Coping, and Social Support1

The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6     

An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI.

Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI.     

New advances in treating osteoporotic compression fractures.

Osteoporosis is a chronic and potentially debilitating disease. A painful consequence of osteoporosis is a compression fracture of a vertebral body of the spine. These fractures can lead to physical deformities and emotional trauma. Treatment options for these fractures are limited and occasionally ineffective. New surgical advances in treating vertebro-compression fractures are evolving. Kyphoplasty is a new surgical procedure now being used to treat the painful compression fracture.     

TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.

Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM.     

Evolution of Learning in Three Aplysiid Species: Differences in Heterosynaptic Plasticity Contrast with Conservation in Serotonergic Pathways

We investigated the neurobiological basis of variation in sensitization between three aplysiid species: Aplysia californica , Phyllaplysia taylori and Dolabrifera dolabrifera . We tested two different forms of sensitization induced by a noxious tail shock: local sensitization, expressed near the site of shock, and general sensitization, tested at remote sites. Aplysia showed both local and general sensitization, whereas Phyllaplysia demonstrated only local sensitization, and Dolabrifera lacked both forms of learning. We then investigated a neurobiological correlate of sensitization, heterosynaptic modulation of sensory neuron excitability by tail-nerve stimulation. We found (1) an increase in sensory neuron (SN) excitability after both ipsilateral and contralateral nerve stimulation in Aplysia , (2) a smaller and shorter-lasting increase in Phyllaplysia , and (3) no effect in Dolabrifera . Because sensitization in Aplysia is strongly correlated with serotonergic (5-HT) neuromodulation, we hypothesized that the observed interspecific variation in sensitization and SN neuromodulation might be correlated with variation in the anatomy and/or functional response of the serotonergic system. However, using immunohistochemistry, we found that all three species showed a similar pattern of 5-HT innervation. Furthermore, they also showed comparable 5-HT release evoked by tail-nerve shock, as measured with chronoamperometry. These observations indicate that interspecific variation in learning is correlated with differences in SN heterosynaptic plasticity within a backgound of evolutionary conservation in the 5-HT neuromodulatory pathway. We thus hypothesize that evolutionary changes in learning phenotype do not involve modifications of the 5-HT pathway per se , but rather, changes in the response of SNs to the activation of this or other neuromodulatory pathways upon noxious stimulation.     

Enrichment of Glutamate-like Immunoreactivity in Primary Afferent Terminals Throughout the Spinal Cord Dorsal Horn

Although several lines of evidence indicate that glutamate is a neurotransmitter in primary afferent terminals, controversies exist on the proportion and types of such terminals that release glutamate. In the present study quantitative analysis of immunogold labelling was used to assess the presence of glutamate-like immunoreactivity in primary afferent terminals in laminae I – V of the rat spinal cord dorsal horn. Anterograde transport of choleragenoid – horseradish peroxidase from a spinal ganglion and tetramethyl benzidine histochemistry were used to identify primary afferent terminals in laminae I and III – V. Presumed C-fibre terminals in lamina II were identified on morphological criteria (dense sinusoid axon terminals). Primary afferent terminals in all dorsal horn laminae displayed significantly higher levels of glutamate-like immunoreactivity than pleomorphic vesicle-containing profiles in laminae III – IV and large neuronal cell bodies in laminae III – V. The density of gold particles over primary afferent terminals also significantly exceeded the average density of gold particles over laminae II and III – IV. The highest densities of gold particles were present over dense sinusoid axon terminals in lamina II. These findings suggest that glutamate, alone or in combination with other neuroactive compounds, is involved in the transfer of all sensory modalities from primary afferent fibres to dorsal horn neurons.     

An Extension of the Regression of Offspring on Mid-Parent to Test for Association and Estimate Locus-Specific Heritability: The Revised ROMP Method

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP_rev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP_rev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.
ROMP_rev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP_rev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.     

Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow

Vascular smooth muscle cells (VSM) are normally exposed to transmural fluid flow shear stresses, and after vascular injury, blood flow shear stresses are imposed upon them. Since Ca²⁺ is a ubiquitous intracellular signaling molecule, we examined the effects of fluid flow on intracellular Ca²⁺ concentration in rat aortic smooth muscle cells to assess VSM responsiveness to shear stress. Cells loaded with fura 2 were exposed to steady flow shear stress levels of 0.5–10.0 dyn/cm² in a parallel-plate flow chamber. The percentage of cells displaying a rise in cytosolic Ca²⁺ ion concentration ([Ca²⁺]_i) increased in response to increasing flow, but there was no effect of flow on the ([Ca²⁺]_i) amplitude of responding cells. Addition of Gd³⁺ (10 M) or thapsigargin (50 nM) significantly reduced the percentage of cells responding and the response amplitude, suggesting that influx of Ca²⁺ through ion channels and release from intracellular stores contribute to the rise in ([Ca²⁺]_i) in response to flow. The addition of nifedipine (1 or 10 M) or ryanodine (10 M) also significantly reduced the response amplitude, further defining the role of ion channels and intracellular stores in the Ca²⁺ response. © 2002 Biomedical Engineering Society. PAC2002: 8716Uv, 8719Uv, 8716Dg, 8719Ff