Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.     

Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Holmes-like tremor of the lower extremity following brainstem hemorrhage.

Holmes tremor is an arrhythmic, 2- to 5-Hz resting, postural, and kinetic upper extremity movement disorder that occurs weeks to months after acute mesencephalic pathology. We present a patient who developed tremor in three body parts postbrainstem hemorrhage with subsequent hypertrophic olivary degeneration and discuss the relevant clinical evolution. Our case is unique because in addition to expected upper extremity and cervical dystonic head tremors, the patient also developed a severe lower extremity movement disorder, which we believe to be a form of Holmes tremor. Tremor involving the lower extremity in this setting has not been previously reported.     

Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.

Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance.     

Identification and characterization of clonal NK-like cells from channel catfish (Ictalurus punctatus)

TcR alpha, beta, and gamma chain negative cytotoxic NK-like cells were cloned from alloantigen-stimulated PBL obtained from nai;ve channel catfish. Stimulation with allogeneic cells and growth promoting factors are required for their continued in vitro proliferation and cytotoxic activity. These granular cells kill not only the stimulating allogeneic cells, but also unrelated allogeneic targets by a perforin/granzyme-mediated apoptosis pathway. In addition, they are negative for markers that define neutrophils, monocytes/macrophages, and non-specific cytotoxic cells. Although these NK-like clones kill a number of different allogeneic targets, they display interclonal variation in cytotoxicity toward a panel of allogeneic targets, i.e. some clones have no apparent target specificity, while others display a target preference. In addition, flow cytometric analyses revealed that expression of a putative FcmuR, an LFA-1-like molecule, and a putative thymocyte/T cell antigen varies among the different clones, with no clear correlation between surface antigen expression and cytotoxic activity. Although not all clones express a putative FcmuR, it was noted that they all expressed an ITAM containing FcepsilonR gamma chain homolog. This finding suggests that the catfish FcepsilonR gamma chain may potentially be used as an accessory molecule for not only FcmuRs, but also for other unknown activation receptors. These results support the hypothesis that catfish NK-like cells are heterogeneous in terms of target specificities and cell surface phenotype.     

Effect of moderate exercise on salivary immunoglobulin A and infection risk in humans

The incidence of upper respiratory tract infections (URTI) and salivary immunoglobulin A concentrations [IgA_s] of nine individuals were examined during 12 weeks of moderate exercise training, and compared to ten sedentary controls. Changes in maximal oxygen uptake were assessed at initial, mid-point and final evaluations (T1–3), while changes in [IgA_s] and salivary immunoglobulin concentration-salivary albumin concentration ratio ([IgA_s]:[Alb_s]) were monitored at T1 and T3. During the 12 week period, symptoms of URTI were self-recorded daily. During the period of training the level of fitness significantly increased (P<0.05) in the exercise group. The number of days recording symptoms of influenza, but not of cold, and total light URTI symptoms was significantly reduced in the exercise group during the last weeks of training. A significant increase in [IgA_s] and in [IgA_s]:[Alb_s] was found in the exercise group after training. Both [IgA_s] and [IgA_s]:[Alb_s] were significantly related to the number of days showing symptoms of influenza (P<0.01) and the total number of days of sickness (P<0.05). These data provide quantitative support for the belief that regular, moderate exercise results in an increased [IgA_s] at rest and [IgA_s]:[Alb_s], which may contribute to a decreased risk of infection. Electronic Publication     

Sexual assault and other types of sexual harassment by workplace personnel: a comparison of antecedents and consequences

Although sexual assault by workplace personnel is widely viewed as a type of sexual harassment, little is known about whether these overlapping constructs may possess some unique characteristics. This article compares the theoretical antecedents and consequences of sexual assault by workplace personnel and other types of sexual harassment among 22,372 women employed in the U.S. military. Path analysis revealed that low sociocultural and organizational power are associated with an increased likelihood of both types of victimization. Organizational climate and job gender context are directly associated with sexual harassment but are only indirectly associated with sexual assault by workplace personnel. Both types of victimization are associated with a variety of negative outcomes, but the pattern of negative consequences differs.     

Use of gene chip technology for the characterisation of the regulation of renal transport processes and of nephrotoxicity in rats

Gene expression profiling using microarrays (rat-specific array RG-U34A, Affymetrix, U.S.A.) was employed for the investigation of: (1) hormonal regulation of renal function and (2) nephrotoxicity. For this purpose about 8,800 genes were analysed in kidney and, additionally, in liver tissue.

Ad 1.) Kidney functions develop during postnatal life. Thus, in vivo transport and accumulation of p-aminohippurate (PAH) was investigated on renal cortical slices (RCS) from 10- and 55-day-old rats. The animals were treated with dexamethasone (DEXA; 60 μg/100 g b.wt./day) for 3 days, which caused a significant reduction in the accumulation of PAH in 10-day-old rats (42 ± 5% whereas it was only slightly reduced in 55-day-old rats (70 ± 8%). To further clarify the regulation of renal function by DEXA, results were compared with those obtained previously after in vitro stimulation with DEXA. RCS were incubated for 24 hours in DEXA-containing medium (10⁻⁹ M). Under these conditions DEXA significantly increased the PAH uptake capacity in RCS obtained from 10- and 55-day-old rats up to 126 and 136%, respectively. Thus a stimulation of tubular transport capacity is possible in vitro. The effect of DEXA treatment on the gene expression of the kidney (in vivo) was moderate. Focussing especially on transporters, ion channels, ATPases, glucuronyltransferases, glutathione-S-transferase and cytochrome P450, the expression of only few genes were significantly changed (3 to 50-fold up- or down-regulation). Moreover, distinct age differences were found after in vivo administration of DEXA. The investigation of in vitro effects of DEXA is currently been performed.

Ad 2.) The kidney is threatened by nephrotoxins because of its ability to accumulate them. We used a single administration of uranyl nitrate (UN; 0.5 mg/100 g b.wt.) as a model for chronic renal failure (CRF). Clearance experiments were performed 10 weeks after UN administration (maximal symptoms of CRF) in adult female rats. As expected, UN induced interstitial cicatrices with reduced GFR and diminished PAH transport capacity. Despite the impressive morphological and functional changes in the kidney after exposure to UN, the gene expression profiles in the kidneys were only minimally affected: we found significantly changed expression levels for only 20 genes (5 genes were up-regulated [e.g. transgelin], 15 down-regulated [among these the Na-K-Cl-symporter, insulin-like growth factor, kallikrein, and ornithine decarboxylase). The lack of agreement between gene expression data and the nephrotoxic effects of UN can probably be explained by the long time interval between dosing and the assessment of the effect. The results confirm that primary genomic responses are likely to be strongest transiently after exposure and then decrease in intensity.