Compartmentalized cAMP/PKA signalling regulates cardiac excitation–contraction coupling

The sympathetic control over excitation–contraction coupling (ECC) is mediated by the cAMP/PKA signalling pathway. However, in the myocyte, the same signalling pathway is responsible for triggering a plethora of diverse intracellular functions the control of which must be independent of the regulation of ECC. Here we discuss what are the molecular mechanisms leading to selective modulation of ECC in cardiac myocytes with a particular focus on the role of spatial confinement of PKA subsets and the compartmentalization of cAMP.     

Anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis

The aim of this work was to shed light on the anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis and to determine any possible changes undergone during the depuration process. To this end, the distribution of two DSP toxins—okadaic acid and DTX2—and some of their derivatives were studied by means of HPLC/MS at different stages of the depuration process. Mussels were collected from mussel farms located in the Galician Rías and they were collected under three types of circumstances: (a) while ingesting toxic phytoplankton cells; (b) 1 week after the toxic cells had disappeared from the water; and (c) after ca. 2 months of depuration. Additionally, in case (b), the distribution among tissues was checked every week over a depuration period of 35 days in the laboratory. DSP toxins were only detected in non-visceral tissues when the extracts were concentrated 20-fold and, even in these cases, the concentrations found were very low. When the maximum possible contribution of non-visceral tissues was computed, taking into account the technique's detection limits and tissue weight, no relevant contribution to the toxin burden of non-visceral tissues was found at any stage of depuration, with the maximum possible contributions usually below 7%. The concentrated samples analysed showed that the actual contribution in all the cases studied was, in fact, less than 1% of the total toxin burden. These findings suggest that (1) when analytical methods are used to monitor DSP toxic mussels, non-visceral tissues should be assumed to be free of toxins in order to precisely compute the toxin concentration of the whole mass of edible tissues and (2) when studying the accumulation kinetics of DSP toxins, transference from the digestive gland to other tissues should not be taken into account, as the other tissues do not contain relevant amounts of DSP toxins.     

Molecular diversity, trafficking and subcellular localization of GABAB receptors

GABA_B receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA). While native studies predicted pharmacologically distinct GABA_B receptor subtypes, molecular studies failed to identify the expected receptor varieties. Mouse genetic experiments therefore addressed whether the cloned receptors can account for the classical electrophysiological, biochemical and behavioral GABA_B responses or whether additional receptors exist. Among G-protein coupled receptors, GABA_B receptors are unique in that they require 2 distinct subunits for functioning. This atypical receptor structure triggered a large body of work that investigated the regulation of receptor assembly and trafficking. With the availability of molecular tools, substantial progress was also made in the analysis of the receptor protein distribution in neuronal compartments. Here, we review recent studies that shed light on the molecular diversity, the subcellular distribution and the cell surface dynamics of GABA_B receptors.     

Self-Organization in Bipolar Disorder: Compartmentalization and Self-Complexity

The present study investigated compartmentalization and self-complexity of self-structure in people with a history of bipolar disorder. Remitted bipolar, recovered depressed and healthy control participants described aspects of themselves using experimenter-provided positive and negative traits. Compartmentalization was assessed by the partitioning of positive and negative traits between self-aspects. Complexity was assessed by both the number of self-aspects people generated and the degree of overlap between the self-aspects. The remitted bipolar and recovered depressed groups demonstrated greater compartmentalization than healthy controls and the remitted bipolar group also demonstrated greater self-complexity than healthy controls when self-aspects relating to the depressed and manic states were included. Compartmentalization may be a generic feature of mood disorder. In addition, bipolar disorder is characterized by a complex, differentiated self-concept with distinctive beliefs about the self in depressed and manic states. Therapeutic implications are discussed.

The expression pattern of SEPT7 correlates with sperm morphology

Purpose

To investigate the expression pattern of the SEPT7 protein during spermatogenesis and its potential role in sperm function.

Methods

We first investigated the expression pattern of SEPT7 during different steps of mouse spermiogenesis using an immunofluorescence assay (IFA). IFA was also applied to study the expression pattern of SEPT7 in human ejaculated spermatozoa. Nine fertile men with normal semen parameters were used as the control group, and 21 infertile men with asthenozoospermia were recruited as the patient group. We assessed the frequency of the SEPT7 signal in the various morphological subgroups.

Results

In humans, the frequency of a defective SEPT7 signal was significantly increased in men with asthenozoospermia. The absence of a SEPT7 signal was more prevalent in sperm containing morphological defects of various types.

Conclusions

The expression pattern of SEPT7 suggested that this protein may be involved in the regulation of subcellular-compartment formation during spermiogenesis in the mouse. The absence of a SEPT7 signal correlated with multiple sperm defects.     

Analysis of Whole Skeleton 3H-Tetracycline Loss as a Measure of Bone Resorption in Maturing Rats

Several modifications of the ³H-tetracycline bone labeling method for measuring whole skeleton bone resorption were tested. Under steady state conditions of whole skeleton resorptive activity, bone labeling for intervals longer than 2 weeks prior to experimentation did not significantly alter the urinary ³H-tetracycline loss curve. The utilization of nonlinear regression analysis showed that the urinary loss of ³H-tetracycline was best described by double exponential equations, indicating the loss of label from two distinct and independent exchangeable bone compartments. This conclusion was supported by the finding that soft tissues were effectively depleted of ³H-tetracycline by 24 hours after the final injection of label. Hence, it was concluded that approximately 40% of the ³H-tetracycline loss from skeletal bone is associated with a ``fast' compartment which is depleted within 6 or 7 days after label loading. The size and rate of <sup>3</sup>H-tetracycline loss from the fast compartment decreased (40%) with age such that the depletion time remained constant between 8 and 24 weeks of age in both male and female rats. The remaining 60% of <sup>3</sup>H-tetracycline loss from a ``slow' compartment which was depleted in about 70 days in young (8 week) rats. This compartment, which is believed to reflect cell-mediated resorption of calcified bone, decreased in size with age in both male (50%) and female (30%) rats. The rate of label loss from this compartment, however, remained relatively high so that the depletion time decreased (∼35%) between 8 and 24 weeks of age. By determining whole skeletal mass and calculating these parameters on the basis of skeletal mass, we were further able to demonstrate significantly higher resorptive activity in female than in male rats by 24 weeks of age. Received: 16 January 1997 / Accepted: 21 May 1997     

CT引导下肺部结节、条块病灶经皮穿刺活检的临床应用

目的:探讨肺部结节病灶、条块病灶CT引导下经皮穿刺活检的诊断价值及检验方法选择.方法:对比分析某医院66例肺部结节病灶、35条块病灶行CT引导下经皮穿刺活检的临床资料、病理及手术、随访资料.结果:66例肺部结节病灶穿刺取材成功65例,2例是凝血块,其中腺癌25例,鳞癌19例,小细胞癌4例,转移癌6例,结核球3例,异常细胞2例,腺瘤2例,硬化性血管瘤1例,支气管囊肿1例;35例肺部条块病灶穿刺成功35例,取材成功28例.诊断炎性病变9例,肺结核6例,鳞癌5例,脓疡4例,腺癌2例,炎性肉芽肿2例.结论:肺部病变CT引导下穿刺活检具有较高的诊断准确率,结节病灶准确率为95%,条块病变准确率为78%,条块病变需要多种方法取材并与病菌检查相结合,以提高穿刺活检断准确率.