Exopolysaccharides from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 prevent influenza virus infection and attenuate secondary bacterial infection risk.

The present study assessed the inhibitory action of exopolysaccharides (EPS) produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 against influenza virus infection followed by secondary bacterial infection. We found that the presence of 200 or 400 µg ml-1 of EPS significantly protected against influenza virus infection in a dose-dependent manner when A549 cells were treated with EPS before infection but not after it. The expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1), an adhesion molecule for bacteria adherence, on A549 cells was significantly enhanced during influenza virus infection compared with viral-non-infected A549 cells. However, this upregulated CEACAM-1 expression was significantly decreased by EPS treatment before viral infection in association with the reduction in the virus titre in A549 cells. In a bacterial adhesion assay using Staphylococcus aureus, the bacterial adherence to viral-infected A549 cells was significantly greater than that to viral-non-infected A549 cells, and the increased bacterial adherence induced by influenza virus infection tended to be decreased by EPS treatment before the infection. Our findings show that EPS treatment before viral infection can inhibit influenza virus infection and alleviate secondary bacterial infection through decreased CEACAM-1 expression.

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels. Abdominal ultrasonography or computed tomography was done every 3 months after surgery. The primary end point for follow-up was recurrence. Seventy-seven of 117 cases (66%) had preoperative levels of the cytokine higher than the borderline limit of 7.5 ng/ml. Postoperative levels were >7.5 ng/ml in 29 of 117 patients (25%). The median follow-up period was 42 months (range, 5--66 months), with follow-up of all 117 patients. No recurrence was observed in 13 patients with Dukes' stage A lesions. Liver metastasis occurred in 18 of 104 patients (17%) with Dukes' stage B or C disease. Fourteen of 18 patients (78%) who developed liver metastasis had shown a postoperative plasma TGF-beta1 level of >7.5 ng/ml. Cox proportional hazards regression analysis showed that the postoperative level was a significant predictive factor for liver metastasis (P < 0.001). A single point measurement of plasma TGF-beta1 levels at 2 weeks after curative resection seems to be able to predict liver metastasis in colorectal cancer. This finding suggests the value of a prospective trial of liver-targeted adjuvant therapy for patients with elevated postoperative plasma TGF-beta1 levels.

Levels of insulin-like growth factors I and II in human cord blood.

Levels of insulin-like growth factors I and II (IGF-I and IGF-II) and somatomedin peptide content (SMPC) were measured in 32 normal term and 11 preterm infants. After acid chromatography to remove somatomedin-binding protein, SMPC was measured by placental membrane radioreceptor assay, while plasma IGF-I and II concentrations were measured by specific RIAs. SMPC levels in term infants were significantly below normal adult levels [0.49 +/- 0.13 (+/- SD) U/ml for infants compared to 1.30 +/- 0.25 U/ml for adult males]. IGF-I levels in term infants were also low, averaging 113 +/- 35 ng/ml for infants; the normal adult levels is 184 +/- 32 ng/ml. The IGF-II level was 282 +/- 84 ng/ml for infants and 687 +/- 169 ng/ml for adults. Both IGF-I and II levels in preterm infants were lower than those in term infants. IGF-I, and IGF-II, and SMPC levels showed a positive correlation with birth weight in term infants. Both IGF-I and IGF-II levels showed a strong positive correlation with gestational age in all infants.

Somatomedins in adolescence: a cross-sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels.

To explore the effect of puberty on the somatomedins (SMs), a group of insulin-like peptides which mediate the action of GH on skeletal tissue, we measured SM-C/insulin-like growth factor-I (SM-C/IGF-I) and IGF-II by specific RIAs in 110 adolescents between the ages of 10 and 18 yr. All subjects were in good health and between the 5th and 95th percentiles for height. In both females and males, SM-C/IGF-I levels rose during puberty to a peak approximately 3-fold higher than the average adult level. The rise in SM-C/IGF-I levels corresponded better with the Tanner stage of the adolescents than with their chronological age. IGF-II levels did not rise during puberty and were slightly below adult levels. The dramatic rise in SM-C/IGF-I levels during puberty suggests a role for this SM peptide in the adolescent growth spurt. Furthermore, these data indicate that proper interpretation of SM-C/IGF-I levels during adolescence must include a knowledge of the patient's pubertal development.

Somatomedins in pregnancy: a cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies.

To explore the role of the somatomedins (SM) during human pregnancy, we have measured plasma levels of insulin-like growth factor I (IGF-I), IGF-II, and SM peptide content (SMPC) in 79 women in various stages of normal pregnancies. IGF-I and IGF-II were measured by specific RIAs, and SMPC was measured by a radioreceptor assay using human placental membranes. IGF-I and SMPC rose during pregnancy, showing a significant positive correlation with the length of gestation. Plasma levels of IGF-I in the third trimester averaged 324 ng/ml, a 33% increase over the first trimester average of 243 ng/ml (P less than 0.05). Although IGF-II did not correlate with the length of gestation, the third trimester average was significantly higher than the first trimester average (780 vs. 630 ng/ml; P less than 0.05). After delivery, both IGF-I and IGF-II levels rapidly dropped to levels significantly below those seen in the third trimester. The gestational rise in SMPC and plasma levels of both IGF-I and IGF-II supports the hypothesis that SM play a role in the regulation of fetal growth.

Lamina propria macrophages in the human gastrointestinal mucosa: their distribution, immunohistological phenotype, and function.

In this study we systematically investigated the cellular distribution, immunohistochemical phenotype, and mucosal disposal function of macrophages in the lamina propria of the human gastrointestinal mucosa (lamina propria macrophages; LPMs). In all tissues examined, most of these LPMs accumulated beneath the epithelial layer that covered the apex of the lamina propria of the mucosa. These cells expressed normal levels of common macrophage markers such as CD68, LN5, lysozyme, ferritin, and alpha 1-anti-chymotrypsin. In addition, they expressed high levels of 25F9 (a market for a certain subpopulation of macrophages), MHC Class II molecules, and CD74 (MHC Class II-associated invariant chain). Interestingly, LPMs possessed some epithelial cell-associated antigens such as cytokeratin, carcinoembryonic antigen (CEA), and Ber-Ep4 in their cytoplasm. Ultrastructurally, these antigens were associated with cellular debris ingested by LPMs, which were recognized as apoptotic fragments by in situ end-labeling. Furthermore, double positive-labeled granules were seen in LPMs by double staining for epithelial cell-associated antigens and in situ end-labeling. These observations suggest that one of the major functions of LPMs is the disposal of apoptotic epithelial cells and that LPMs may be involved in the regulation of mucosal epithelial renewal.

Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy.

Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori. We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN.

Magnetic resonance imaging of human spinal cord infarction.

Magnetic resonance images obtained in two cases of spinal cord infarction are described: one with hemorrhagic thoracic cord infarct, the other with ischemic cervical cord infarct with sequential magnetic resonance imagings. An enlarged cord with strand-shape or longitudinal hypointensity on both T1- and T2-weighted images was noticed in the hemorrhagic infarct; hypointensity on the T2-weighted image was thought to be due to hemosiderin, which shortens T2 relaxation. In the ischemic infarct, a small, round area of hypointensity on T1-weighted images, and of hyperintensity on T2-weighted images, noted 9 hours postictus ("early infarct") changed on the 22nd day to a cephalocaudal strandlike hypointensity on T1-weighted image, which was enhanced by Gd-DTPA. The hypointensity suggested "pencil-like softening" in "medium" age infarct. On postictal day 49, it showed an extensive homogeneous hypointensity involving several segments of the cord on T1-weighted images and hyperintensity on T2-weighted images with negative Gd-DTPA enhancement suggesting "late transverse infarct." We considered that these changes are of value in diagnosing spinal cord infarcts on magnetic resonance imagings.

Spinal giant intradural perimedullary arteriovenous fistula: clinical and neuroradiological study in one case with review of literature.

BACKGROUND: Giant intradural perimedullary arteriovenous fistula with massive spinal cord compression is rare. The therapeutic difficulties include whether endovascular embolization or direct surgical excision should be selected. We present a patient with the largest giant spinal intradural perimedullary arteriovenous fistula shown by magnetic resonance imaging so far reported, who was successfully treated by a combination of endovascular embolization and direct surgery. CASE DESCRIPTION: A 16-year-old girl presented with a giant intradural arteriovenous fistula (perimedullary Type II) at the C4-5 level, manifesting as progressive cervical myeloradiculopathy. The single-hole fistula was supplied by the anterior spinal artery and an ascending artery arising from both the costocervical and highest intercostal arteries with a rapid transit time, and drained superiorly to the foramen magnum, and inferiorly to the thoracic spinal canal, through a huge venous lake at the site of the arteriovenous connection. The patient was treated by transarterial embolization with platinum coils and silk, followed by surgical excision with excellent results at 12 months' follow-up. CONCLUSIONS: We recommend that such a huge perimedullary arteriovenous fistula with a rapid transit time, and severe cord and root compression, should be treated with embolization followed by surgical excision.

[Spinal intramedullary cavernous angioma associated with hematomyelia: case report with sequential MRI follow-up and histological verification of hematoidin deposits].

A 61-year-old woman first experienced sudden lower back and right leg pain 3 years prior to surgery. At this time, MRI showed an intramedullary cavernous angioma at Th10-11 with central T2 high and peripheral T2 low signal intensity. However, she completely recovered in two weeks. Four days prior to the present admission (day of the second hemorrhage), she again experienced severe lower back and right leg pain, followed by complete paralysis of the right leg. Despite vigorous medical treatment including administration of steroid, hemostatics and glycerol, her condition became aggravated with complete paraplegia and loss of sphincter control by the 4th hospital day. MRI taken two days after the second hemorrhage showed an increase of peritumoral T2 hypointensity and another area of T2 hypointensity in the lumbar spinal cord at L1-Th12 with cord swelling. MRI 13 days after the second hemorrhage showed that these areas of T2 hypointensity had changed to T1 and T2 hyperintensity suggesting conversion of deoxyhemoglobin to methemoglobin. Subsequent MRI showed longitudinal punctuate propagation of methemoglobin from the angioma down to the lumbar enlargement and into the conus medullaris, where a 30 x 6 mm spindle-shaped area of T1 and T2 hyperintensity indicating hematomyelia had formed. Total removal of the angioma was followed by gradual recovery and decrease in the size and signal intensity of the hematomyelia. Histopathological examination demonstrated the typical features of cavernous angioma with deposition of hematoidin. Propagation of extravasated blood from the ruptured thoracic cavernoma to the conus medullaris, with splitting of spinal cord nerve fibers, was demonstrated by MRI.

[DAPI-DNA cytofluorometric study of glioma cells--application of DAPI-DNA cytofluorometry to paraffin embedded archival glioma tissue for nuclear DNA content analysis].

Using DAPI-DNA cytofluorometry, the author analyzed nuclear DNA content of formalin fixed, paraffin embedded, glioma material obtained from 14 glioma cases at surgery. Sections of 10 microns were deparaffinized. Following simultaneous DAPI (4,6-diamidino-2-phenylindole dihydroporphyrin chloride)/HP (hematoporphyrin) staining, DAPI binds DNA and DNA-DAPI complexes emit blue fluorescence when exited by ultraviolet (UV) light. Through Zeiss fluorescence microscope, the author measured nuclear fluorescence intensity with histological verification of glioma cells. A DNA histogram was obtained with fluorescence intensity recorded on the abscissa and number of cells plotted on the ordinate. Samples of 20 normal non-neoplastic astrocytes taken from apparently normal brain tissue included in the histological slide were used as diploid (2 C) control. Based on DNA content, tumor cells were classified into 4 groups: N-group composed of cells with 2 C DNA content (normoploid), S-group with less than 2 C (hypoploid), L-group more than 4 C (hypertetraploid), I-group between 2 C and 4 C (intermediate ploidy). Intermediate ploidy was significantly higher and normoploid was significantly lower in glioblastoma compared with those of benign astrocytoma. Thus, DNA content and histological malignancy were well correlated. Due to limitation of measuring diaphragm of turret in the microscope, some extra large cell could not be included in it and was excluded from the measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of sucralfate to duodenal ulcer in man.

Biopsy specimens of ulcerated and of adjacent non-ulcerated duodenal mucosa were obtained from 17 patients with active duodenal ulcer who had received a single oral dose of 1 g sucralfate. Similar specimens were obtained from 21 patients with a recently healed duodenal ulcer. The specimens were assayed for aluminum to provide an estimate of the amount of sucralfate bound to the mucosa. Sucralfate was present at significantly higher concentrations in ulcerated mucosa than in non-ulcerated mucosa for 6 hr after dosing. In addition, sucralfate was found to bind to healed duodenal ulcers for 6 hr after dosing. This finding provides a rational basis for the use of sucralfate in the maintenance therapy of duodenal ulcer.

Effect of sucralfate on ethanol-induced gastric mucosal damage in the rat.

We studied the effect of sucralfate on ethanol-induced gastric mucosal damage in the rat. In doses of 25, 50, 100, 200, 400 and 800 mg/kg given 1.5 hr before the oral administration of 3 g/kg ethanol, sucralfate inhibited the development of erosions by 36, 62, 72, 90, 98 and 100 percent, respectively. Cimetidine, up to a dose of 160 mg/kg, was ineffective in this model. Sucralfate, in a dose of 400 mg/kg, also decreased the drop in transmucosal potential difference produced by the intragastric instillation of 3 ml of 20% ethanol from 21 mV to 13 mV. In separate experiments, pylorus-ligated rats received 125I-labeled human serum albumin intravenously and the leakage of 125I-radioactivity into the gastric lumen was studied as a parameter of mucosal permeability to macromolecules. Ethanol, in a dose of 3 g/kg, produced a two-fold increase in leakage over control. This was prevented by sucralfate (250 mg/kg) when given either 1.5 hr before or 3 hr after the dose of ethanol. The results of these experiments suggest that sucralfate protects the gastric mucosa against ethanol-induced damage by enhancing mucosal resistance.

[Interferon therapy after ablation of Kent bundle for a patient with chronic hepatitis type B complicated with WPW syndrome].

Cardiotoxicity of interferon-alpha or gamma, such as fatal arrhythmia and myocardial infarction, has been reported. Therefore cardiotoxicity of interferon should be seriously considered before administration for patients with a pre-existing heart disease. We treated a patient with chronic active hepatitis type B, coexisted with Wolff-Parkinson-White syndrome, who has had frequent attacks of paroxysmal atrial fibrillation. To prevent the occurrence of fatal arrhythmia with an interferon therapy in this patient, we performed radiofrequency catheter ablation of the Kent bundle. After the successful ablation, we could safely administered recombinant interferon alpha-2b for chronic hepatitis type B.