A case of Fabry's disease detected by renal biopsy findings

A 39 year-old man was found to have mild proteinuria by urinary examination since one year ago. He was for the first time diagnosed as having Fabry's disease by histopathological and electronmicroscopic findings of the renal biopsy specimens, which showed the presence of numerous vacuolated cells and electron dense bodies inside the cells. The level of WBC alpha-galactosidase was significantly lower than normal level. The pedigree of this patient showed a familial history of various types of renal disease. One of the patient's brothers also showed decreased level of WBC alpha-galactosidase, who has been treated by maintenance hemodialysis for 2 years. It is concluded that early diagnosis of this disease through renal biopsy and WBC alpha-galactosidase level is important to manage the future course of patients with Fabry's disease.     

A role of fibrinolytic activity in angiogenesis. Quantitative assay using in vitro method

The functional role of the fibrinolytic system in capillary growth was investigated using bovine capillary endothelial cells (BCEs) cultured on a Type I collagen gel matrix, into which the cells migrated to form capillary-like tubular structures. The length of the tubes formed were measured morphometrically using an image analyzer in the absence and presence of fibrinolytic proteases, namely plasminogen, plasminogen activators (PAs) and PA inhibitor (PAI). The addition of plasminogen (25 micrograms/ml) to the gel matrix significantly increased the length of BCE tubes found on the 9th day of culture (p less than 0.01), with a dose-dependent tendency. The simultaneous addition of a basic fibroblast growth factor (bFGF, 10 ng/ml) enhanced this tube formation as early as the 3rd day of culture (p less than 0.01). Cultured BCEs secreted both tissue-type and urokinase-type PAs (tPA and uPA) and PAI-1 into the culture medium, and the secretion of both PAs was enhanced by the addition of bFGF. However, the secreted tPA was composed mostly of an inactive form of tPA.PAI-1 complex, and the PA activity was derived mostly from uPA. Inhibitors of plasmin suppressed the enhancing effect of plasminogen on angiogenesis. In addition, anti-uPA IgG markedly inhibited the enhancing effect of plasminogen on the 4th and 7th days of culture (p less than 0.01), whereas anti-tPA IgG showed an inhibitory tendency only on the 4th day of culture (p less than 0.05). These findings indicate that the plasminogen-PAs system, especially uPA synthesized and secreted by BCEs, plays an important role in regulating angiogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Needle tract implantation of thymoma after transthoracic needle biopsy.

A 73 year old woman was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under fluoroscopic observation. The histopathological diagnosis was thymoma and combination chemotherapy was given. The tumour almost completely disappeared and the patient was discharged. But the tumour recurred in the left anterior chest wall four months later. It is suggested that the thymoma tissue had been implanted in the needle tract.     

Isoelectric focusing spectra of anti-bacterial alpha-amylase antibody unique for antigen-induced suppression.

The effect of intravenous (i.v.) administration of bacterial alpha-amylase (B alpha A) on the IgG antibody response to a subsequent challenge with B alpha A in incomplete Freund's adjuvant (IFA) varied with the difference in responsiveness of the parental strains. High-responder C3H/He (C3) mice given injections of either 200 or 4 micrograms of B alpha A, which alone were unable to trigger a detectable IgG antibody response, generated an enhanced response to an immunogenic challenge given 25 days after the last i.v. injection. The response of low-responder C57BL/6 (B6) mice previously exposed to B alpha A, following a different kinetic course depending on the exposing dose, reached a plateau lower than the levels of control responses (tentatively designated as high- and low-zone suppression). Prior exposure of (B6 X C3)F1 hybrids to 200 micrograms led to the enhanced response, whereas pretreatment with 4 micrograms rendered them partially tolerant to a subsequent challenge. These results suggest that the capacity to achieve low-zone suppression is inherited as a dominant trait. Isoelectric focusing (IEF) analysis revealed that these enhanced responses expanded antibody heterogeneity in a strictly restricted, strain-specific manner as observed during the normal antibody response, although the rate of expansion was accelerated. The specific antibodies produced by individual high-zone suppressed B6 mice were focused as a limited set of bands in a narrow pH range where the specific antibodies produced early in the normal response were focused. In contrast, the response of low-zone suppressed B6 and F1 hybrid mice was characterized by a unique process of heterogeneity expansion.     

Ingestion of High β-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects

The prebiotic effect of high β-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.     

Total hip arthroplasty using hydroxyapatite-coated cementless cup for rapidly destructive coxarthrosis: Minimum 10-year follow-up

BackgroundPerforming total hip arthroplasty (THA) as early as possible is recommended for rapidly destructive coxarthrosis (RDC) as it causes pain that becomes progressively more severe. However, acetabular bone loss remains an issue in THA. Special devices, such as a Kerboull-type plate, may be used for acetabular bone defects, but the procedure is highly invasive and often the patients are elderly, further complicating matters. We retrospectively investigated the clinical and radiographic results of THA using conventional hydroxyapatite-coated cementless cup in RDC.MethodsA total of 32 patients (35 hips) with RDC were enrolled in the study with a minimum 10-year follow-up. All THAs were performed using conventional hydroxyapatite-coated cementless cup. All patients were evaluated clinically according to the Harris hip score (HHS). Acetabular bone deficiency was classified according to the American Academy of Orthopaedic Surgeons (AAOS) classification.ResultsEleven hips (31%) were AAOS type III, and none were type IV. Total HHS significantly improved from 36.5 to 79.4 (p < 0.01). Two cups exhibited loosening. The overall implant-associated survival rate after 10 years was 91.4%.ConclusionsClinical results of THA using conventional cementless implants for patients with RDC were acceptable. Thus, THA using conventional cementless implant is an effective and safe surgery for patients with RDC, minimizing surgical stress.     

Alveolar soft part sarcoma, granular cell tumor, and paraganglioma. An immunohistochemical comparative study

Five cases of alveolar soft part sarcoma, 5 cases of granular cell tumor, and 6 cases of paraganglioma were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, desmin, and glial fibrillary acidic protein (GFAP], actin, myoglobin, and nervous tissue markers (S-100 protein, neuron-specific enolase, and Leu-7). In alveolar soft part sarcomas, some of the tumor cells were positive for desmin, but negative for nervous tissue markers. The tumor cells of granular cell tumors were stained with anti-S-100 protein antibody, but not with anti-neuron-specific enolase antibody. In contrast, the tumor cells of paragangliomas were positive for neuron-specific enolase, but not for S-100 protein except for stellate cells surrounding the tumor cell nests. This immunohistochemical approach was valuable for the differential diagnosis of these three tumors. Furthermore, the complete absence of cytokeratin in all of the tumor cells may be helpful in distinguishing these three tumors from metastatic carcinoma in soft tissue. The histogenesis of alveolar soft part sarcoma is a matter of controversy. The result that besides desmin actin was also demonstrated in some of the tumor cells may support the myogenic origin of this tumor.     

Effects of GM1-ganglioside and α-sialyl cholesterol on amino acid uptake,protein synthesis,and Na+, K+-ATPase activity in superior cervical and nodose ganglia excised from adult rats

We examined the effect of GM₁-ganglioside in combination with cholera toxin B, and synthetic α-sialyl cholesterol (α-SC) on neutral amino acid (tritiated α-aminoisobutyric acid, [³H]AIB) uptake, protein synthesis ([³H]leucine incorporation), and Na⁺, K⁺-ATPase activity in isolated superior cervical ganglia (SCG) and nodose ganglia (NG) from adult rats after aerobic incubation, usually for 2 h at 37°C in vitro. Cholera toxin B, that specifically masks the oligosaccharide chain of GM₁-ganglioside, antagonized the GM₁-induced changes in [³H]AIB uptake, [³H]leucine incorporation, and Na⁺, K⁺-ATPase activity almost completely in SCG, but partially in NG. Although cholesterol itself had little effect on either [³H]AIB uptake and Na⁺, K⁺-ATPase activity both in SCG and NG, α-SC caused considerable reduction of both amino acid uptake and the transport enzyme activity in each ganglia. However, cholesterol was more effective than α-SC in decreasing [³H]leucine incorporation in either ganglia. Whereas addition of EGTA markedly reduced either GM₁-induced or α-SC-induced change in [³H]leucine incorporation into acid-insoluble fraction in both SCG and NG, application of Ca²⁺ ionophore produced considerable recovery of the protein synthesis from the inhibited level by Ca²⁺-deprivation. ATP and creatine phosphate contents in SCG were elevated by the presence of GM₁ or α-SC, whereas [³H]AIB uptake and Na⁺, K⁺-ATPase activity were inhibited, suggesting that utilization for membrane transport was diminished as a result of GM₁- or α-SC-induced decrease of ATPase activity.     

Retrovirus-mediated gene-transfer of tnf receptor for treatment of cancer

Tumor necrosis factor-alpha receptor cDNA (TNFR-1 or TNFR-2) was inserted into a retrovirus derived vector. Recombinant vector was transfected into packaging cell line. The transfectants producing high titer of virus containing TNFR-1 or TNFR-2 cDNA were obtained. Human stomach cancer cells that poorly expressed TNFR-1 or TNFR-2 were infected with this virus as an in vitro model experiment of gene therapy. The stomach cancer cells that were infected with recombinant virus expressed TNFR-1 or TNFR-2 and were effectively killed by recombinant TNF.