A case of bronchocentric granulomatosis presenting as a tumorous shadow on chest X-ray film]

A 57-year-old woman was admitted to our hospital with cough, sputum and abnormal chest X-ray. In summer, 1989, she developed cough which gradually worsened in autumn. In November, the chest X-ray revealed a tumorous shadow in the left suprahilar region. On admission, there were no symptoms of bronchial asthma. Chest X-ray revealed a subpleural tumorous shadow in the left upper lung field. X-ray findings suggested that the tumorous shadow in the suprahilar region moved to the left peripheral upper lung field. Left B1+2 orifice obstruction with necrotic tissue was seen on fiberoptic bronchoscopy. Transbronchial biopsies failed to yield specific diagnostic findings, except for bronchitis with exudate containing eosinophils. In February, 1990, she developed hemosputum and left chest pain. Chest X-ray showed consolidation in the left apical lung field. Left upper lobectomy was performed. Histological examination disclosed many granulomas with central necrosis around the bronchi, and aspergillus hyphae were seen. These findings are compatible with bronchocentric granulomatosis without asthma.     

A nonspecific colonic ulcer occurring after hepatectomy: Report of a Case

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Metalloproteinase activity is present in rat urine and derived from the renal cortex

Summary: Matrix metalloproteinases (MP) are important candidates for the degradation of extracellular matrix, but the role of MP in the diseased kidney remains poorly understood. to examine the significance of urinary MP, we first investigated the characteristics of MP in normal rat urine and renal cortex, and then evaluated the urinary MP activity in anti-thymocyte induced glomerulonephritis (Thy.1 GN). Metalloproteinase activity was measured as the EDTA-inhibitable degradation of [³H] gelatin. the enzyme was purified from urine and the renal cortex homogenate in normal Wistar rats by using several chromatographic and gel filtration methods. Both materials contained the identical molecular weight (Mr 126 kDa by gel permeation method) of gelatin-degrading enzymes, the activity of which was inhibited by metal chelating agents and reactivated by ZnC1₂ but not by other proteinase inhibitors. Thy.1 GN was induced by intravenous injection of rabbit anti-thymocyte serum into rats, and daily urine was collected at sequential time points. Urinary MP activity was markedly reduced soon after the serum injection, and returned to the control level in 9 weeks. Conversely, urinary MP-inhibitor activity (Mr 30 kDa), determined as inhibiting activity against MP derived from renal cortex, showed serial changes strikingly reflected as urinary MP activity. These findings suggested that rat urine contained the MP which seemed to be derived from the renal cortex, and the urinary MP activity was decreased in Thy.1 GN model, probably due to the presence of MP-inhibitor. As urinary MP is likely to reflect intra-renal MP, the evaluation of urinary MP may be useful to search metabolic alteration of extracellular matrix in the diseased kidney.     

Association of myopathy with large-scale mitochondrial dna duplications and deletions: Which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6–kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.     

Hydrostatic pressur influences mRNA exprssion of trnsforming growth factor-β1 and heat shock protein 70 in chondrocyte-like cell line

The present study investigated the influence of hydrostatic prssure on the exprssion of cytokines and heat shock protein 70 in a chondrocyte-like cell line. Chondrocyte-like cells (HCS-2/8) were exposed to hydrostatic pressur by a special pressure apparatus. Total RNA for cytokines (interleukin-1β, basic fibroblast growth factor, insulin-like growth factor-I, and transforming growth factor-β1) and for heat shock protein 70 was extracted and was analyzed by a polymerase chain reaction method and Northern blotting. An assay for incorporation of [³⁵S]sulfate was performed to assess proteoglycan synthesis. The expression of transforming growth factor-β1 mRNA was enhanced after exposure to 5 Mpa of hydrostatic prssure and was reduced after 50 Mpa, whereas the expression of heat shock protein 70 was enhanced following exposure to 50 Mpa of hydrostatic pressure. The incorporation of [³⁵S]sulfate into the cultured cells increased following exposure to 1-5 Mpa of hydrostatic pressure and decreased following 10-50 Mpa of pressure. These results suggest that hydrostatic pressure at physiologic levels enhances the expression of transforkming growth factor-β mRNA in addition to increasing proteoglycan synthesis in chondrocytes and that excessively high hydrostatic pressure reduces the expression of transforming growth factor-β1 mRNA and increases the expression of heat shock protein 79 mRNA while decreasing proteoglycan synthesis.     

Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.

The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region.     

Hemodynamic Parameters Influencing Clinical Performance of Novacor Left Ventricular Assist System

The interrelationships between hemodynamic variables including right ventricular (RV) performance with filling/ejection dynamics of the Novacor left ventricular assist system (LVAS) were determined in 10 of 11 patients who received LVAS as a bridge to heart transplant. Nine were successfully transplanted. Data were obtained intraoperatively, at periodic intervals up to 48 h postimplant and at explant. The hypotheses investigated included (a) RV performance influences LVAS filling characteristics and (b) LVAS pump output is influenced by systemic vascular resistance (SVR). During the period of LVAS support (2-126 days), pumping characteristics included a mean filling volume of 51 ml (range, 24-70), residual volume of 4.9 ml (range, 1-18), pump rate of 113/min (range, 63-175), and pump output of 5.81/min (range, 2.8-8.2). Multiple regression analysis identified pulmonary vascular resistance (PVR), RV stroke work index (RVSWI), and pulmonary capillary wedge pressure, but not RV ejection fraction, pulmonary artery pressure, or central venous pressure (CVP) as the most important correlates with LVAS filling volume (p less than 0.001, R2 = 0.6). In addition, LVAS pump output was influenced mainly by RVSWI, PVR, and SVR (p less than 0.001, R2 = 0.7). It was concluded that LVAS performance is highly dependent on RV function and systemic/pulmonary vascular resistances.     

Cyclic adenosine monophosphate production and contractile response induced by beta-adrenoceptor subtypes in rabbit urinary bladder smooth muscle

The spontaneous contractile force of muscle strips isolated from male rabbit urinary bladder dome [detrusor) and base (trigonal muscle) was dose dependently inhibited by isoproterenol, a non-specific beta-adrenoceptor agonist. The relaxant response to 10(-6) M isoproterenol in the detrusor muscle was completely blocked by butoxamine (10(-4) M), a selective beta-2-antagonist, and by propranolol (10(-6) M), a non-specific beta-antagonist, but not by metoprolol (10(-6) to 10(-4) M), a selective beta-1-antagonist. Relaxation of trigonal muscle induced by 10(-6) M isoproterenol was inhibited 30% by metoprolol (10(-5) M), 70% by butoxamine (10(-4)M), and 100% by propranolol (10(-6) M). Terbutaline, a selective beta-2-adrenoceptor agonist, also caused dose dependently a relaxant response in detrusor and trigonal muscle. The maximum relaxant responses to isoproterenol and terbutaline were significantly greater in detrusor than in trigonal muscle. Dobutamine, a relatively specific beta-1-adrenoceptor agonist, caused a small but significant relaxant response in trigonal, but no change in detrusor muscle. In trigonal muscle the relaxant response to dobutamine was less than that to terbutaline. Cyclic adenosine monophosphate accumulation in detrusor did not significantly increase after administration of dobutamine, but significantly increased after administration of terbutaline. On the other hand, not only terbutaline, but also dobutamine, markedly increased cyclic adenosine monophosphate accumulation in trigonal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ultraviolet B irradiation on lenticular riboflavin metabolism and high-molecular-weight-protein aggregation

We investigated the effects of ultraviolet B (UVB) irradiation on the formation of ester forms of riboflavin and of high-molecular-weight (HMW) protein aggregates and on lenticular riboflavin-binding capacity (LRBC). Esterification of riboflavin decreased as the duration of UV irradiation increased, suggesting the irradiation-induced denaturation of the apoenzyme of synthetases of ester forms of riboflavin. UVB irradiation of lens homogenate supplemented with riboflavin increased LRBC and the formation of HMW protein aggregates, while gamma-crystallin was decreased. These results are consistent with those of our earlier studies in which we obtained data suggesting that, upon exposure of rat lens homogenate to fluorescent light, photosensitized riboflavin may bring about cross-linking of lens protein. Our data demonstrate that the photosensitivity of lenticular riboflavin is increased by longer periods of UV irradiation.