Expression of alpha-smooth muscle actin in liver diseases.

To evaluate the distribution of alpha-smooth muscle actin (alpha-SMA) positive cells in various liver diseases, we undertook an immunohistochemical study of liver diseases including chronic persistent hepatitis, chronic active hepatitis, liver cirrhosis, intrahepatic cholelithiasis and hepatocellular carcinoma. As a control, fetal livers (gestational age: 22-26 weeks) showed alpha-SMA positive cells along the blood vessels of the portal area, terminal hepatic venules and at perisinusoidal spaces. Perisinusoidal alpha-SMA positive cells were bipolar shaped and had round nuclei. In chronic persistent hepatitis, a few alpha-SMA positive cells were admixed with the inflammatory infiltrates mostly along the intact limiting plate. They were also detected multifocally in a linear pattern along the dilated sinusoid. In chronic active hepatitis, very strong alpha-SMA staining was detected at the site of piecemeal necrosis and adjacent lobules. A-SMA expression was decreased in some cases after interferon treatment. In cases of transplanted liver biopsies, expression of intralobular alpha-SMA was diffusely increased but showed no correlation with degree of acute rejection. Cirrhotic livers revealed strong alpha-SMA positivity in fibrous septae as well as in the perisinusoidal space of intact hepatocytes at the leading edge of fibrosis. Interlobular bile ducts were concentrically circumscribed by alpha-SMA positive cells in cases of intrahepatic cholelithiasis. In trabecular type hepatocellular carcinomas, most sinusoidal lining cells were positive for alpha-SMA. Most intralobular alpha-SMA positive cells represent, if not all, perisinusoidal cells (PSCs) which are involved in intralobular fibrogenesis in various liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced neutrophil functions by recombinant human granulocyte colony-stimulating factor in diabetic patients with foot infections in vitro

This study was performed to evaluate the effect of granulocyte-colony stimulating factor on neutrophil functions in diabetic patients with active foot infections in vitro. Twelve diabetic patients with foot infections and 12 normal volunteers were enrolled. Neutrophils from peripheral blood were incubated with granulocyte colony-stimulating factor (G-CSF, 50 ng/mL) for 20 min. Superoxide production of neutrophils was measured by the reduction of ferricytochrome C. Neutrophil phagocytosis was assayed using Staphylococcus aureus and the weighted phagocytic index was calculated. Superoxide production of neutrophils in diabetic patients with foot infections was 7.7 (unit: nmol/2 x 10(5) cells/60 min), which was significantly lower than that in controls (12.0) (p<0.05). G-CSF increased neutrophil superoxide production to 12.1 in diabetic patients with foot infections and to 19.8 in controls (p<0.05 for each). Weighted phagocytic index in diabetic patients with foot infections was 0.77, which was not significantly different from that of the controls (0.69). Weighted phagocytic index was increased significantly by G-CSF to 0.88 in diabetic patients with foot infections and to 0.79 in controls (p<0.05 for each). In conclusion, G-CSF significantly enhanced neutrophil functions in diabetic patients with foot infections in vitro.     

Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6 +/-2.6 yr) were consecutively recruited. Geno-mic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1 *15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1 *06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3 * 0202 (100%), HLA-DRB1 * 1302 (67%), HLA-DRB3 * 0301 (67%), and HLA-DQB1 * 0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1 * 1501 (40%) and HLA-DRB5 * 0101 (40%) were significantly increased in children with ADEM. HLA-DRB1 * 1401, HLA- DRB3 * 0202, and HLA-DQB1 * 0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1 * 15 and DQB1 * 06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1 * 1501, HLA-DRB5 * 0101, HLA-DRB3 * 0301, and HLA-DQB1* 0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3 * 0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.     

Inflammatory pseudotumor of the lung in a child with mycoplasma pneumonia

A case of inflammatory pseudotumor of the lung occurring in a six-year-old boy is reported with clinicopathologic findings, including its ultrastructure. The patient had had frequent upper respiratory tract infections, and one and half year before the discovery of the lung mass, he suffered from pneumonia of the right lung, which was serologically proven to be a mycoplasma pneumoniae infection. Exploratory thoracotomy revealed a large mediastinal mass that was removed together with the right middle and lower lobes of the lung. The mass arose from the lung with an endobronchial element. Microscopically, the mass was composed of a variety of inflammatory and mesenchymal cells, including plasma cells, histiocytes, lymphocytes, and fibroblast-like spindle cells. Ultrastructurally, the spindle-shaped mesenchymal cells were either fibroblasts or myofibroblasts. At the time of diagnosis of the inflammatory pseudotumor of the lung, the serum titer of antimycoplasma antibody rose again, and the lung parenchyma adjacent to the mass showed interstitial pneumonia with features of bronchiolitis obliterans. The present case suggests that the inflammatory pseudotumor of the lung could be a postinflammatory lesion associated with mycoplasma pneumoniae infection.     

Development of a miniature scintillation camera using an NaI(Tl) scintillator and PSPMT for scintimammography

We have developed a small scintillation camera dedicated to breast imaging and have evaluated the performance of the system. In order to increase the limited field of view (FOV) determined by the size of a position-sensitive photomultiplier tube (PSPMT), the imaging characteristics of a diverging hole collimator (DHC) were also investigated. The small scintillation camera system consists of an NaI(Tl) crystal (60 mm x 60 mm x 6 mm) coupled to a Hamamatsu R3941 PSPMT, a resistor chain circuit, preamplifiers, nuclear instrument modules, an analogue to digital converter and a PC for control and display. The intrinsic energy resolution of the system was 12.9% FWHM at 140 keV. The spatial resolution was measured using a line-slit mask and 99mTc point sources and was 3.1 mm FWHM. The intrinsic sensitivity of the system was approximately 162 counts/s kBq(-1). The DHC made it possible to image a larger FOV (75 x 75 mm2 at the surface of collimator) than a parallel-hole collimator (60 x 60 mm2). The system sensitivity obtained using the DHC gradually decreased with distance (3% at 1 cm, 6% at 2 cm and 9% at 3 cm). The results demonstrate that the system developed in this study could be utilized clinically to image malignant breast tumours. A DHC can be employed to expand the FOV of the system confined by the size of PSPMT with a modest compromise in the performance of the system.     

The utility of multi-detector row spiral CT for detection of coronary artery stenoses

Contrast-enhanced multi-detector row spiral computed tomography (MDCT) was introduced as a promising noninvasive method for vascular imaging. This study examined the accuracy of this technique for detecting significant coronary artery stenoses. Both MDCT(Sensation 16, Siemens, Germany, 12x0.75 mm collimation and 0.42 sec rotation speed, 120 kV, 500 effective mA, and 2.7 mm/rotation table-feed) and invasive coronary angiography (CAG) were performed on 61 patients (mean age 59.2+/-10, 44 men) who were suspected of having coronary artery disease. All patients were treated with atenolol (25-50 mg) prior to imaging and the heart rate was maintained below 65 beats per minutes during image acquisition. The images were reconstructed in the diastole around TI-400 ms with a 0.5 mm increment and a 1.0 mm thickness. All coronary arteries with a diameter of 2.0 mm or more were assessed for the presence of a stenosis (>50% luminal narrowing). Two independent radiologists who were unaware of the results of the invasive CAG evaluated the MDCT data, and the results were compared with those from the invasive CAG (interval 1-27, mean 11 days). An evaluation of the CT coronary angiogram (CTCA) was possible in 58 of the 61 patients (95%). Image acquisition of the major coronary arteries including the left main trunk was available in 229 out of 244 arteries. Invasive CAG showed that 35 out of 58 patients had significant coronary artery stenoses by. patient analysis of those who could be evaluated showed that CT coronary angiography correctly classified 30 out of 35 patients as having at least 1 coronary stenosis (sensitivity 85.7%, specificity 91.3%, positive predictive value 93.8%, negative predictive value 80.8%). By analyzing each coronary artery, CAG found 62 stenotic coronary arteries in the 229 coronary arteries that could be evaluated. MDCT correctly detected 50 out of 62 stenotic coronary arteries and an absence of stenosis was correctly identified in 156 out of 167 normal coronary arteries (sensitivity 80.6%, specificity 93.4%, positive predictive value 81.9%, negative predictive value 92.8%). The non-invasive technique of MDCT for examining the coronary artery appears to be a useful method for detecting coronary artery stenoses with a high accuracy particularly with the proximal portion and large arteries.     

Anti-IgM induces up-regulation and tyrosine-phosphorylation of heterogeneous nuclear ribonucleoprotein K proteins (hnRNP K) in a Ramos B cell line

Heterogeneous nuclear ribonucleoprotein K protein (hnRNP K) has diverse molecular partners implicated in signal transduction pathways, and is tyrosine-phosphorylated in response to growth factors and oxidative stress. Among the structurally distinct domains of hnRNP K, an SH3-binding domain (SH3BD) has been known to promote the association of SH3-containing tyrosine kinases and protooncoprotein Vav, which are involved in B cell receptor (BCR) signalling. In this study, we analyzed proteins of Ramos B cell line that are altered upon BCR activation with anti-IgM antibody, revealing that a certain hnRNP K isoform is up-regulated in response to anti-IgM treatment. We also showed that hnRNP K is tyrosine-phosphorylated after BCR ligation. HnRNP K lacking the SH3BD is shown not to interact with phosphorylated Vav, and Ramos cells stably expressing this mutant protein are less susceptible to anti-IgM-induced apoptosis, indicating that hnRNP K is coupled to BCR-mediated signalling and its SH3BD is required for proper signal propagation. Our results provide the first evidence that hnRNP K is involved in BCR signalling pathway.     

Endodermal sinus tumor: immunophenotypic expression of a carcinoma.

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.