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Aims/Introduction Thrombin exerts various pathophysiological functions by activating protease‐activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria. Materials and Methods Plasma HCII activity and spot urine biomarkers, including albumin and liver‐type fatty acid‐binding protein (L‐FABP), were determined as the urine albumin‐to‐creatinine ratio (uACR) and the urine L‐FABP‐to‐creatinine ratio (uL‐FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females). Results The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate‐regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log‐transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL‐FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log‐transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively). Conclusions The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early‐stage DKD development, as represented by albuminuria., Plasma HCⅡ activity is significantly and inversely associated with urinary albumin excretion but not liver‐type fatty acid‐binding protein in Japanese patients with diabetes.

Basophilic inclusions (BIs), which are characterized by their staining properties of being weakly argyrophilic, reactive with Nissl staining, and immunohistochemically negative for tau and transactive response (TAR) DNA-binding protein 43 (TDP-43), have been identified in patients with juvenile-onset amyotrophic lateral sclerosis (ALS) and adult-onset atypical ALS with ophthalmoplegia, autonomic dysfunction, cerebellar ataxia, or a frontal lobe syndrome. Mutations in the fused in sarcoma gene (FUS) have been reported in cases of familial and sporadic ALS, and FUS immunoreactivity has been demonstrated in basophilic inclusion body disease (BIBD), neuronal intermediate filament inclusion disease (NIFID), and atypical frontotemporal lobar degeneration with ubiquitin-positive and tau-negative inclusions (aFTLD-U). In the present study, we immunohistochemically and ultrastructurally studied an autopsy case of sporadic adult-onset ALS with numerous BIs. The patient presented with the classical clinical course of ALS since 75 years of age and died at age 79. Postmortem examination revealed that both Betz cells in the motor cortex and motor neurons in the spinal cord were affected. The substantia nigra was spared. Notably, BIs were frequently observed in the motor neurons of the anterior horns, the inferior olivary nuclei, and the basal nuclei of Meynert. BIs were immunopositive for p62, LC3, and FUS, but immunonegative for tau, TDP-43, and neurofilament. Ultrastructurally, BIs consisted of filamentous or granular structures associated with degenerated organelles with no limiting membrane. There were no Bunina bodies, skein-like inclusions, or Lewy-like inclusions. All exons and exon/intron boundaries of the FUS gene were sequenced but no mutations were identified.

Characterization of low microgram levels of glycoprotein remains a challenge due to extensive heterogeneity of the conjugated N-glycans at each individual glycosylation site. We present an optimized, sensitive workflow for glycopeptide isolation and characterization that exploits the complementary features of RP (Poros R2) and hydrophilic (zwitter-ionic hydrophilic interaction chromatography) chromatographic resins. The glycopeptide analysis workflow was applied to human β2-glycoprotein I (β2-GPI, apolipoprotein H), which contains multiple N-glycosylation sites. Conditions for rapid proteolytic digestion of β2-GPI using low-specificity proteases were optimized to detect β2-GPI glycopeptides by MS. We demonstrate the importance of ensuring sufficient column capacity of both hydrophobic and hydrophilic stationary phases for optimal glycoprofiling by MS. The enriched glycopeptides were characterized using MALDI quadrupole TOF MS/MS. A total of 23 glycan structures, including sialylated bi- and tri-antennary complex type glycans, were characterized at three N-glycosylation sites, namely Asn-143, Asn-174 and Asn-234, of β2-GPI. Further exploration of the complementary nature of RP and HILIC stationary phases for glycopeptide isolation prior to MS analysis may eventually enable systematic analysis of complex glycoprotein samples in functional proteomic research and advance our understanding of the biological role of protein glycosylation.

A 6-year-old Japanese girl presented with psychomotor seizures. Magnetic resonance (MR) images disclosed a mass lesion in the left middle cranial fossa with an internal irregular-shaped area, which was hyperintense on T1-weighted images and hypointense on T2-weighted images. Gross total resection of the tumor was performed through left occipital craniotomy. The tumor was white-to-grayish hard tissue, focally showing blackish pigmentation. Histological, immunohistochemical and electron-microscopical analyses revealed that white-to-grayish hard tissue corresponded to an atypical meningioma, and the blackish pigmentation of the tumor was composed of non-neoplastic, reactive hyperplasia and colonization of meningeal melanocytes in the meningioma tissue. A meningioma with reactive hyperplasia and colonization of meningeal melanocytes is unusual, but it is clinically important to differentiate this entity from other melanocytic tumors.

BACKGROUND Transforming growth factors β (TGFs β) are involved in a variety of important cellular functions, including cell growth and differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs β are correlated with angiogenesis. However, the role of TGF-β as an angiogenic factor in gastric carcinoma is still unclear. METHODS TGF-β1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compared in the current study with both the expression of vascular endothelial growth factor (VEGF), which is thought to be the most potent angiogenic factor, and microvessel density, to evaluate the effect of TGF-β1 on the angiogenesis of gastric carcinoma tissues. RESULTS TGF-β1 expression was detected in 23 tumors (22.8%). TGF-β1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-β1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-β1 expression and VEGF expression. There was no correlation between TGF-β1 expression and microvessel density, whereas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients with TGF-β1 positive tumors and 67.0% in patients with TGF-β1 negative tumors. Accordingly, the prognosis for patients with TGF-β1 negative tumors was significantly better than that for patients with TGF-β1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-β1 expression were independent prognostic factors. CONCLUSIONS These results suggest that TGF-β1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma. Cancer 1999;86:1455–62. © 1999 American Cancer Society.

We present a rare case of Alexander's disease occurring in a 10–year-old girl with convulsive seizures. She initially developed gait disturbance and thereafter deteriorated mentally. At 48 years of age she died of cumulative convulsive seizures. The postmortem examination revealed a generalized and focally pronounced deposition of Rosenthal fibers in the deep cerebral white matter around the lateral ventricles. Atypical fibrillary glia, diffuse patchy demyelination and circumscribed cystic necrosis were also observed. An electron microscopic examination of the cerebral white matter revealed not only irregular, densely osmiophilic bodies merging in places with glial filaments, but also well-developed hemidesmosomes associated with anchorage densities in the perivascular astrocytes. The subplasmalemmal anchorage densities usually received glial fibrils, which were frequently intermingled with Rosenthal fibers. Thus, our case can be added to the small number of previously reported cases demonstrating a juvenile form of Alexander's disease based on both clinicopathologic features and on ultrastructural appearance, and our case also confirms the profound involvement of astrocytes.

Background: The pN classification of gastric cancer (GC) in the Japanese system (Japanese Gastric Cancer Association; JGCA) is based on the site and distance of metastatic nodes from the primary tumour. Union International Contra Cancer (UICC) has recently proposed a classification system based on the number of nodes involved (TNM-1997). The aim of the present study is to assess which classification system is more suitable for providing a prognosis in advanced GC with lymph node metastasis. Methods: A total of 224 patients who underwent curative gastrectomy (R0: UICC−TNM and Resection A and B: JGCA) and D2 lymphadenectomy between 1990 and 1999, and diagnosed as pT2, pT3 and pT4 GC were enrolled. Patients were followed until the end of 2002. The disease-free survival rates of patients were compared between the two-stage systems (UICC−TNM and JGCA). Results: Using the JGCA system, there was a significant difference between the two survival curves (pN0 and pN1, P = 0.025; pN1 and pN2, P

The satellite-borne antenna is large due to the requirement for a high gain and a multibeam operation. The construction is soft to reduce the weight as much as possible. Therefore, it is difficult to carry out the performance evaluation test on the ground with the configuration in the orbit. This paper presents a method for accurate evaluation of a large antenna in orbit. First, the electrical test results on the ground with a weight deformation made as small as possible is compared with the numerical results based on the measured values of the manufacturing errors so that the evaluation error is obtained. Next, the performance in orbit is obtained by adding the evaluation error to the values computed from the measured fabrication error and assembling error and thermal deformation analysis value. The present procedure was applied to a Ka-band multibeam antenna with an aperture diameter of 3.5 and 2.5 m on board the ETS-VI satellite. It is shown that the evaluation can be done with sufficient accuracy.

This paper describes a method of evaluating the difference in chromatin content of cervical cancer cells and normal cells by applying image processing techniques. Among the various methods for texture analysis, this paper adopts structural analysis to achieve high accuracy. The analysis procedure is as follows. (1) The location of chromatin is determined by extracting the pixel where the gray level is locally maximum. (2) The image is segmented by any of Volonoi neighborhood, area expansion by a difference direction, or directed tree. (3) Threshold processing is applied to the segmented subimages. (4) The size and gray level of the extracted areas are determined. A feature extraction experiment for the cell is perormed by the above procedure. From these results, the following observations are obtained. (i) The method of local maximum is useful in determining the chromatin location. (ii) The extraction can be improved by local thresholding. (iii) The mean, variance and mean gray level of the cell in the extracted chromatin area, as well as the mean and variance of the minimum distance among local maxima, are seen to be useful feature parameters in the discrimination of normal and malingnat chromatins.

We report a case of sporadic amyotrophic lateral sclerosis (ALS) characterized by a marked accumulation of neurofilaments in the cytoplasm of neurons. The neurofilament was identified by immunohistochemical and electron microscopic studies. The distribution of the accumulation in this case was unique, not only in the motoneurons of the anterior horn but also in the neurons of the other areas of the spinal gray matter, some nuclei in the brain stem, pontine reticular formation, substantia nigra, dentate nucleus in the cerebellum and pyramidal cells in the motor cortex. These observations shed light on the pathogenesis of ALS.

Neurotoxic effects of adriamycin (ADM) were examined in rats. The drug was administered through retrograde axoplasmic transport from the transected sciatic nerve in very small amounts (0.05 mg of adriamycin). Using the autofluorescence specific to adriamycin as a histological tracer, alterations in primary sensory neurons in dorsal root ganglia (DRG) and in motor neurons in the spinal cord were observed chronologically by light and electron microscopy. In the DRG at the fifth and sixth lumbar levels, small neurons initially showed alterations in mitochondria, wavy nuclear membranes and enlarged cisternae of rough endoplasmic reticulum, and disappeared early in the experiments. Large neurons, which showed accumulation of neurofilaments, dense bodies and vacuoles in the perikarya in addition to nucleolar and nuclear chromatin alterations, degenerated slowly. In contrast, motor neurons in the anterior horn at the sixth lumbar level survived throughout the administration of adriamycin despite the presence of transient weak adriamycin autofluorescence and vacuoles in the cytoplasm. Thus, the susceptibility and vulnerability of motor neurons in spinal cord to adriamycin differed from that of primary sensory neurons; small neurons in the DRG were more susceptible than large sensory neurons. Administration through retrograde axoplasmic transport proved to be a useful technique for the evaluation of the neurotoxicity of adriamycin without the complications of systemic effects.

Life history and resource utilization pattern were compared between two closely related mite species of the genusTetranychus. 1. Tetranychus urticae developed more quickly and had a higher oviposition rate thanT. kanzawai. Consequently, the potential for population increase was greater forT. urticae than forT. kanzawai but the difference was slight. 2. T. urticae was more tolerant of a deteriorating food resource and/or over-crowding.T. kanzawai responded more sensitively to food deterioration and dispersed more quickly. 3. There was a considerable difference between injury patterns by the two species.T. kanzawai damaged host plants more severely, causing earlier and more extensive defoliation of the plants. 4. The maximum population size achieved byT. urticae was 2 to 3 times greater than that ofT. kanzawai on potted host plant. This showed that the former could utilize a food resource much more efficiently.

Polarization diplexing is possible by means of a grid plate and hence a frequency reuse antenna can be realized. Usually, the characteristics of a grid plate can be evaluated by an analysis based on an equivalent circuit. However, for a practical grid with a support mechanism made of dielectric or honeycomb structures, the reflection level of the unwanted polarization at the time for transmission of the desired wave is larger than the value for the metal grid only and hence the results are different from those by the equivalent circuit analysis. In this paper, the characteristics of the grid with a dielectric support layer are analyzed by means of full-wave analysis so that the relationship between the thickness of the dielectric support layer and the reflection level of the unwanted polarization is detected. Next, a method is proposed for suppression of this unwanted polarization in a grid with a dielectric support layer. The validity was confirmed by theoretical analysis and experiments. Further, the design method and the numerical results are presented for a low-loss polarization diplexing grid used in a frequency reuse antenna. It is pointed out that there exists an optimum parameter that minimizes the insertion loss in the operating bandwidth.