Autonomic Regulation of Voltage-Gated Cardiac Ion Channels

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na_V1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by β adrenergically stimulated G-proteins. We demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na_V1.5, Ca_V1.2a, and K_V1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.     

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.     

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

An ultrastructural study of cartilage resorption at the site of initial endochondral bone formation in the fetal mouse mandibular condyle

An ultrastructural study was undertaken on cartilage resorption at the site of initial endochondral bone formation in the mouse mandibular condyle on d 16 of pregnancy. After resorbing the bone collar, the osteoclasts extended their cell processes into the cartilage matrix and made contact with hypertrophic chondrocytes. By means of cell processes or vacuolar structures, these osteoclasts entrapped the calcified cartilage matrices, cell debris, and the degraded uncalcified cartilage matrices. In particular, since the calcified cartilage matrices were sometimes seen to be disrupted within the osteoclastic vacuolar structures, they were probably disposed of by the osteoclasts. Invading endothelial cells giving rise to capillaries also directly surrounded the degraded uncalcified cartilage matrices and small deposits of cell debris. In addition, hypertrophic chondrocytes that had attached to or were in the process of attaching to the invading osteoclasts often enclosed the small calcified cartilage matrices. Other cell types that have often been reported in other regions of cartilage resorption were not seen at the site of initial endochondral bone formation in this study. Our findings in relation to cartilage resorption may therefore represent unique features of the site of initial endochondral bone formation site. We consider that the manner of cartilage resorption is likely to vary by site, age, and species.     

Evaluation of Mini Mental State Examination and Brief Psychiatric Rating Scale on aged schizophrenic patients

Abstract  Mini Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS) and subscales of the BPRS were performed on 73 elderly inpatients (mean age: 67.9 years; standard deviation: 7.2; range: 60–89) diagnosed with DSM-III-R chronic schizophrenia. Forty of the subjects were men and 33 were women. A significant negative correlation was observed between MMSE and the age, factor negative, factor depressive, and total score of BPRS. We believe, however, that it is relatively sufficient to screen for demented illness of schizophrenics using MMSE when considering the age and the psychiatric symptoms (especially negative or depressive symptoms). Forty-eight (66%) of the 73 patients were categorized as 'demented' by MMSE. These results suggest that the aged inpatients with schizophrenia in a hospital showed certain kinds of cognitive deficits (including senile dementia) more frequently than the general population.     

Frequency and Output-Dependent Change in Conduction Over Slow Pathways in a Patient with Sustained Ventricular Tachycardia Unrelated to Coronary Artery Disease

In a patient with sustained ventricular tachycardia, we obtained two different paced QRS morphologies from a single pacing site. In one QRS morphology the stimulus to the QRS complex was long, 150 msec, and in the other it was 100 msec. At the paced cycle length of 600 msec and the stimulus output of 4 V, one QRS morphology with the stimulus to the onset of QRS activation (St-QRS) interval of 150 msec was observed. At the paced cycle length of 400 msec, the other QRS morphology with a St-QRS interval of 100 msec was observed alternatively with the former. At the paced cycle length of 353 msec or 316 msec, the latter with a shorter St-QRS interval was exclusively observed. When the stimulus output was increased from 4 to 10 V, keeping with the paced cycle length at 400 msec, the St-QRS interval was shortened from 100 to 80 msec. For the two QRS morphologies with two St-QRS intervals, two slowly conducting pathways would be responsible. The site of the block in the faster pathway must be located at the proximity of the pacing site and the conduction at a shorter paced cycle length would be explained by "supernormal conduction."     

Diffuse fibromatosis on the scalp in infancy: A variant of juvenile hyaline fibromatosis

Various types of fibromatosis have been reported in infancy and early childhood. We describe an infant with diffuse fibromatosis on the scalp. A one year and five months-old girl showed a diffuse and hard mass 3 × 5 cm in diameter and no tenderness on the scalp. Two months later, the size of the mass had increased and several other tumors appeared on the lateral head. The magnetic resonance imaging (MRI) disclosed that a large and diffuse tumor had spread from the frontal to occipital head; a ‘helmet-like’ configuration of the tumor was exhibited on sagittal MR images. The tumor showed high signal intensity on T2-weighted images and was enhanced with Gd-DTPA. Histological examination showed a fibroblastic proliferation with intervening thick collagen bundles. The patient was diagnosed as having diffuse fibromatosis. The tumor at the resection site immediately recurred, whereas the tumor in the frontal head showed marked regression. Three months after the resection, new tumors appeared in the occipital head. The size and number of these tumors have remained unchanged for more than 18 months. The sites and appearance of the tumors were identical to that of juvenile hyaline fibromatosis (JHF) in this patient. However, JHF usually includes fibroblasts associated with large amounts of hyalinized collagen-like material, which were not present in our patient. The different histology of JHF comparing our case and other reported cases may depend on the different phase of the disease progression at resection. Long-term observation is necessary for the appropriate diagnosis and evaluation of prognosis in this patient.     

An Operating Microscope with Higher Magnification and Higher Resolution for Cerebral Aneurysm Surgery: Preliminary Experience—Technical Note

We describe a higher magnifying power operating microscope system to improve one method of high-quality microsurgical clipping for cerebral aneurysm in some cases. This higher magnification is achieved by a new lens design in the optical system, which makes the image of the object very clear at high magnifications (distinctiveness of 7 μm). This higher-resolution operating microscope system provides the surgeon with higher-magnified images (at the maximum of more than 30× magnifications as each working distance) in the operating field. The magnifications can be changed from low power (2.9×) to high power (62.0×) depending on the circumstances in a given procedure. We have used this operating microscope system on 11 patients with microsurgical clipping for cerebral aneurysms. Microsurgical treatment could be performed safely and precisely. All aneurysms were treated without any technical complications. We think that the use of this microscope would have potential benefits for microsurgical treatment for cerebral aneurysms because of better visualization.     

Dermoscopic evaluation of vascular structures of various skin tumors in Japanese patients

Dermoscopic analysis of skin tumor has been mainly focused on pigmented structures. Recently, several different morphological types of vessels were found to be well associated with pigmented or non‐pigmented skin tumors in white subjects. Therefore, the recognition of such vascular structures has been applied for diagnostic purposes. As little statistical information on the various pigmented skin tumor vessels of Japanese patients has been reported, we therefore tried to evaluate the association between various vascular structures and 741 tumor lesions of Japanese patients. Vascular structures were dermoscopically recognized in 41 of 102 cases of melanoma, 104 of 119 basal cell carcinoma (BCC), 86 of 257 seborrheic keratosis (SK), 35 of 210 dermal and compound nevus (DN/CN), six of 12 squamous cell carcinoma (SCC) and 16 of 41 Bowen disease (BD). The structures of arborizing and glomerular vessels statistically revealed diagnostic specificity for BCC and BD, respectively, and hairpin vessels were helpful for differentiating SK from other pigmented tumors, as already reported in white patients. The most common vascular pattern observed in melanoma was the linear–irregular structure, but this pattern in Japanese patients had less diagnostic value than in white patients, because its sensitivity was not significantly higher than in SCC. The most remarkable differences between our study and previous reports with white patients were low frequency and sensitivity of dotted, comma and polymorphous vessels in lesions of melanoma, BCC and DN/CN; these vessels had less diagnostic value for Japanese patients. Finally, the frequency of vascular structures observed in melanoma rose along with the increase of the Breslow’s tumor thickness, and 88% of melanomas with vascular vessels revealed tumor thicknesses of more than 2 mm.     

The safety of a nitric oxide inhalation system using a conventional infant respirator

Attention is becoming increasingly focused on inhalation of nitric oxide (NO) as a selective pulmonary vasodilator. Its metabolite nitrogen dioxide (NO₂), however, is a toxic molecule. The purpose of the present study was to evaluate the safety of a NO inhalation system using a conventional infant respirator from the viewpoint of NO₂ production. The NO inhalation system consisted of a standard neonatal ventilator, a neonatal circuit and a test lung. The NO concentration was increased from 0 up to 19 ppm. At each level of NO, the oxygen (O₂) concentration was changed from 21 to 100%. The NO and NO₂ concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO₂ concentration was increased when either the O₂ or the NO concentration was increased. The maximum concentration of NO₂ was 0.10 ± 0.02 ppm when the concentrations of NO and O₂ were 19 ppm and 100% respectively. The NO inhalation system, using a conventional infant respirator, can be used safely when monitoring NO and NO₂ concentrations.