Analysis of variance study of the rat cortical layer 4 barrel and layer 5b neurones

Unique formation of rodent cortical barrels by layer 4 neurones attracts study of the sensory function of cortical input stage neurones (layer 4) compared with that of output stage neurones (layer 5). We have recorded extracellular responses from rat somatosensory cortical neurones to deflections of contralateral vibrissae. Thirty-two layer 4 barrel neurones and 29 layer 5b neurones were studied. Whisker stimulations were ramp-and-hold deflections with one of six different ramp velocities (100–2.5 mm s⁻¹) and one of four different plateau amplitudes (2000–200 μm). Twenty-four (6 × 4) different stimulus forms were applied to the tip of a whisker trimmed to 10 mm in a predetermined order in stimulus cycles of 20–50 repetitions. Spike counts for a period of 2560 ms in 10 ms bins were summed to construct a matrix of 24 peristimulus histograms for each neurone. Twenty-four amplitude and 24 velocity values were computed from counts during the plateau and ramp phases, respectively. To determine the amplitude- and velocity dependence of a neurone, an amplitude F value (the ratio of variations among-/within-amplitude of the amplitude value) and a velocity F value (ratio of variations among-/within-velocity of the velocity value) were derived by analysis of variance. The amplitude F value of the layer 4 barrel neurones was greater than that of the layer 5b neurones ( P < 0.0001). The velocity F value of the barrel neurones was smaller than that of the layer 5b neurones ( P = 0.0226). The results suggests that barrel neurones and layer 5b neurones tend to detect amplitude and velocity components of whisker deflection, respectively.     

Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Antitumor activities of KW-2152, a new isoquinon agent, against human tumor xenografts transplanted into nude mice

The antitumor activities of KW-2152, a new isoquinon derivative, were examined in thirteen human tumor xenografts, transplanted into nude mice. KW-2152 was administered intravenously at a schedule of q4d X 3, in daily doses of 7.3 mg/kg and 3.6 mg/kg, and q2d X 6 with a daily doses of 7.3 mg/kg, respectively. KW-2152 displayed significant antitumor activities against the human tumor xenografts in 3 out of 13 strains (23.1 per cent) at the schedule of q4d X 3, with a daily dose of 7.3 mg/kg. Depending on the schedule of administration, tumor activity was observed in 8 out of 13 strains (61.5 per cent) at a schedule of q2d X 6, with a daily dose of 7.3 mg/kg. SH-2 and SH-9 gastric tumors were sensitive to KW-2152 and growth was completely inhibited with the schedule of q4d X 3, and a daily dose of 7.3 mg/kg. Thus, KW-2152 seems to have a wide antitumor spectrum, and the possible antitumor effects for clinical use, warrant attention.     

Fluid-fluid levels in cavernous hemangioma of soft tissue

Five cases of cavernous hemangioma with fluid-fluid levels on magnetic resonance imaging and/or computed tomography are reported. The signal characteristics were those of blood and histological analysis of the fluid-fluid levels showed that they were blood-filled cavities in the tumor. Although this finding itself is not specific, it may help in confirming the diagnosis of cavernous hemangioma.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat

The topical organization of thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat has been studied using the technique of retrograde axonal transport of horseradish peroxidase. The projections of the posterolateral and posteromedial ventral nuclei (VPL, VPM) to the second somesthetic area (SII) are organized somatotopically. The posterior portion of SII (hindlimb area) receives fibers mainly from the dorsolateral part of VPL, the middle portion of SII (forelimb area) from the ventromedial part of VPL, and the anterior portion of SII (face area) from VPM. These topical projections are more loosely organized and less densely arranged than those to the first somesthetic area. The SII receives a few fibers from the medial geniculate nucleus, particularly its magnocellular and dorsal principal parts, and from the suprageniculate nucleus. The posterior part of SII lying near the secondary auditory area receives many fibers from the medial geniculate and suprageniculate nuclei, and only a few fibers from the lateral central and paracentral nuclei. The fourth somesthetic area (SIV), located in the dorsal bank of the anterior ectosylvian sulcus, receives fibers mainly from the dorsal principal and magnocellular parts of the medial geniculate nucleus, and from the suprageniculate nucleus. The SIV receives a fair number of fibers from VPL and VPM roughly in a somatotopical manner. The posterior portion of SIV receives fibers chiefly from the dorsolateral part of VPL, the middle portion of SIV from the ventromedial part of VPL, and the anterior portion from VPM. In addition, SIV receives a few fibers from the lateral central, paracentral, ventral lateral and ventral medial nuclei. The SIV, together with the most posterior part of SII, forms an auditory area, receiving many fibers from the medial geniculate and suprageniculate nuclei, and a few fibers from the intralaminar nuclei.     

Development and Initial Testing of a Permanently Implantable Centrifugal Pump

Abstract: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo-lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.     

The effect of histamine on cultured endothelial cells. A study of the mechanism of increased vascular permeability.

The role of endothelial cells in the histamine-induced vascular response was investigated using cultured endothelial cells obtained from human umbilical veins. A single population of histamine H1 receptors was detected in these cells by means of a [3H]mepyramine binding assay. Its Kd was 0.74 +/- 0.07 nM and Bmax was 41.4 +/- 8.68 fmol/mg protein. Actin filaments were distributed as dense bands at the margin of the cells and as sparse microfilament bundles traversing the center of the cells. Histamine caused a decrease in peripheral bands and an increase in longitudinal bands. The changes evoked by histamine were dose-dependent, related to the duration of incubation of the cells with histamine, and blocked by mepyramine, a histamine H1 receptor antagonist. The results suggest that the endothelial cells respond to histamine through the histamine H1 receptor. This may explain one of the mechanisms of histamine-induced vascular response including vascular permeability increase.