Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3

The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.     

Radial artery running beneath the biceps tendon and its interrelation between the radial recurrent arteries

A radial artery running beneath the biceps tendon was found in the cadaver of a Japanese woman during a student dissection course at Kumamoto University School of Medicine in 2006. The brachial artery bifurcated into the radial artery and the ulnar artery in the cubital fossa, and the radial artery twisted laterally running beneath the biceps tendon, and when it was situated laterally to the tendon, twisted distally at the level of the radial tuberosity, and then twisted medially again. After the radial artery passed over the biceps tendon, it turned distally and continued as a normal radial artery. The superficial brachial artery, which coexisted with the brachial artery, was given off from the axillary artery and it continued to the final twist of the radial artery. The course of this radial artery is similar to the arterial rings surrounding the biceps tendon, found during the same dissection course. The arterial rings were formed between the brachial artery and the radial artery, and their proximal origins ran beneath the biceps tendon, while the distal origins were superficial. The present arterial variation is thought to have occurred when the normal part of the radial artery in the cubital fossa was substituted by the arterial ring, coexisting with the superficial brachial artery, which usually disappears during normal development. Furthermore, it is suggested that a part of the arterial ring always remains as a radial recurrent artery.     

A middle meningeal artery which arises from the internal carotid artery in which the first branchial artery participates.

A middle meningeal artery arising from the internal carotid artery was found in the right half of the head of an 85-year-old male cadaver during student dissection practice. It arose from the lateral aspect of the internal carotid artery in the carotid canal, arrived at the foramen lacerum after running forward. It then ran backward under the trigeminal ganglion and took the usual course after passing its posterior margin. On one hand, the maxillary artery did not issue the middle meningeal artery, gave off only a small twig supplying the lateral pterygoid muscle at the corresponding position. It was corroborated by the fact that the foramen spinosum was absent in this example. During usual development, the middle meningeal artery primarily springs from the supraorbital branch of the stapedial artery that arises from the dorsal part of the second branchial artery. Later, by the formation of the external carotid artery connecting with the common trunk of the infraorbital and mandibular branches (maxillomandibular division) of the stapedial artery and by the atrophy of the proximal part of it, the middle meningeal artery is finally supplied by the external carotid artery. But in this example, it is supposed that the middle meningeal artery arose from a more distal position of the internal carotid artery owing to the persistence of the anastomosis between the dorsal part of the first branchial artery and the supraorbital branch and the interruption of the connection between the supraorbital branch and maxillomandibular division of the stapedial artery.     

Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Changes of cerebral vasoactive intestinal polypeptide-and somatostatin-like immunoreactivity induced by noise and whole-body vibration in the rat

To clarify the role of vasoactive intestinal polypeptide (VIP) and somatostatin, somatropin-release inhibiting factor, (SRIF) neurons in the response to organisms to noise or whole-body vibration stress, VIP and SRIF-like immunoreactivity were determined in various regions of the rat brain following exposure for 90 min to noise (broad band, 102 dB) or whole-body vibration (20 Hz, 4.0 g). Both noise and whole-body vibration significantly increased VIP-like immunoreactivity in the amygdala. A significant reduction of VIP like immunoreactivity in the hippocampus was induced only by whole-body vibration. On the other hand SRIF-like immunoreactivity was decreased significantly in the hypothalamus and increased significantly in the amygdala by noise and whole-body vibration, respectively. The present findings would seem to indicate that the amygdalofugal VIP neural system is involved in regulating hypothalamic and pituitary hormone secretions in non-specific reactions to stress. Responses of hippocampal VIP and the amygdalofugal SRIF to whole-body vibration stress are assumed to be activated as specific reactions to the stress.     

Fragmented red cells are the major cause of spuriously high platelet counts in patients with fragmented red cells when counts are obtained by automated blood cell counter

Platelet counts measured by automated blood cell counter often show spuriously high values when measuring samples contain particles of equal size to platelets. The major cause of spuriously high platelet counts in samples with fragmented red cells (FRC) is thought to be the FRC themselves. We studied the correlation between FRC and spuriously high platelet counts in 40 patients demonstrating FRC on blood smears. FRC were measured by manual hemocytometry and by flow cytometry using a monoclonal antibody against glycophorin A (GPA method). There was a significant correlation between spuriously high platelet counts and FRC by manual hemocytometry (r=0.60, p<0.001) or FRC by the GPA method (r=0.45, p<0.005). These data suggest that FRC are the major cause of spuriously high platelet counts in samples with FRC.     

Dopamine and serotonin: influences on male sexual behavior

Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.     

Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium

The endometrium is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.