The cellular mechanisms for spiral wrapping and compaction of myelin sheaths by oligodendrocytes are not known yet. In this study, we examined the role of fyn tyrosine kinase, which could be responsible for molecular events during the stage of myelination in the CNS. Western blot and immunohistochemical analyses revealed that fyn-deficient mice have significantly lower levels of myelin basic protein (MBP), which is required for intracellular membrane adhesion parts so-called major dense line (MDL) and thought to be essential for the stability of myelin sheath. Electron microscopy verified that the myelin ultrastructure could be used to distinguish fyn-deficient mice from wild-type mice, showing a thin and redundant myelin sheath in the corpus callosum. Further, the electron-dense 'major' line in myelin from the purified myelin fractions remained condensed, and myelin compaction was split opened in fyn-deficient mice. To determine whether there was a change in the microheterogeneity of MBP due to a post-translational event we first investigated peptidylarginine deiminase (PAD), which is an enzyme that converts arginine residues in peptides to citrulline residues. PAD immunoreactivity was observed both in the myelin from fyn-deficient and wild-type mice. By Western blot analysis we found an increase of the citrullined form of MBP. In addition, MBP from fyn-deficient mice did weakly induce vesicle aggregation properties of MBP-mediated adhesion. We concluded that although oligodendrocytes from fyn-deficient mice are able to wrap around the axon, they are unable to form compact myelin due to decreased MBP level and the presence of increased citrullinated MBP.

Animals↗

PubMed2000

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Cerebral Cortex↗

PubMed2000

Repulsive axon guidance molecule Sema3A inhibits branching morphogenesis of fetal mouse lung.

Semaphorin III/collapsin-1 (Sema3A) guides a specific subset of neuronal growth cones as a repulsive molecule. In this study, we have investigated a possible role of non-neuronal Sema3A in lung morphogenesis. Expression of mRNAs of Sema3A and neuropilin-1 (NP-1), a Sema3A receptor, was detected in fetal and adult lungs. Sema3A-immunoreactive cells were found in airway and alveolar epithelial cells of the fetal and adult lungs. Immunoreactivity for NP-1 was seen in fetal and adult alveolar epithelial cells as well as endothelial cells. Immunoreactivity of collapsin response mediator protein CRMP (CRMP-2), an intracellular protein mediating Sema3A signaling, was localized in alveolar epithelial cells, nerve tissue and airway neuroendocrine cells. The expression of CRMP-2 increased during the fetal, neonate and adult periods, and this pattern paralleled that of NP-1. In a two-day culture of lung explants from fetal mouse lung (E11.5), with exogenous Sema3A at a dose comparable to that which induces growth cone collapse of dorsal root ganglia neurons, the number of terminal buds was reduced in a dose-dependent manner when compared with control or untreated lung explants. This decrease was not accompanied with any alteration of the bromodeoxyuridine-positive DNA-synthesizing fraction. A soluble NP-1 lacking the transmembrane and intracellular region, neutralized the inhibitory effect of Sema3A. The fetal lung explants from neuropilin-1 homozygous null mice grew normally in vitro regardless of Sema3A treatment. These results provide evidence that Sema3A inhibits branching morphogenesis in lung bud organ cultures via NP-1 as a receptor or a component of a possible multimeric Sema3A receptor complex.

Animals↗

PubMed2000

Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir.

Two patients complained of severe abdominal pain as the first sign of varicella zoster virus infection about 1 year after allogeneic BMT. In case 1, eruptions, found on the face and chest on admission, became vesicular and dispersed on the third hospital day. Though acyclovir (ACV) was immediately started, he died on the fourth day. In case 2, skin rash was never observed during the clinical course. Laparotomy on the third hospital day revealed many hemorrhagic spots on the liver surface and mucous membrane of the upper GI tract, indicating disseminated visceral disease. Empiric therapy with ACV was successful.

Abdominal Pain↗

PubMed2000

Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings in a patient undergoing unrelated bone marrow transplantation.

A 23-year-old woman underwent HLA-matched unrelated BMT for CML. She developed cerebral blindness on day 81. Brain magnetic resonance imaging revealed hyperintensity on a T2-weighted image in the white and gray matter of the right frontal and both occipital lobes. Single-photon emission computed tomography (SPECT) was consistent with a decrease in radionuclide uptake in these areas, suggesting a vasoconstrictive mechanism. A diagnosis of CsA-induced encephalopathy was made and CsA was discontinued. Her vision recovered completely after 24 h and abnormal imaging resolved within 2 weeks. This case demonstrates late onset CsA-induced cerebral blindness with the previously unreported abnormalities on SPECT.

Aged↗

PubMed2000

Diagnosis and management of cystic pancreatic tumours with mucin production.

BACKGROUND: To aid selection of the most appropriate treatment for intraductal tumours (IDTs) and mucinous cystic tumours (MCTs) of the pancreas, this study describes the clinical and diagnostic features of these tumours and compares the clinicodiagnostic features of malignant and benign tumours and hyperplasia. METHODS: The clinical features of 28 IDTs (four cases of hyperplasia, six adenomas and 18 adenocarcinomas) and six MCTs (four adenomas and two adenocarcinomas) were studied. RESULTS: An IDT was found in 24 men and four women with a mean age of 64.5 years, whereas all patients with an MCT were women, with a mean age of 50.8 years. Twenty IDTs were located in the pancreatic head, whereas all MCTs were in the pancreatic body-tail. The mean size of IDTs was smaller than that of MCTs (4.4 versus 7.7 cm). The mean size of hyperplastic lesions, adenomas and adenocarcinomas in IDTs were 1.7, 2.9 and 5.4 cm respectively. Hyperplastic IDT lesions were smaller than 2 cm without either mural nodules or dilatation of the main pancreatic duct. IDTs larger than 3 cm with mural nodules and mucin secretion from an enlarged papilla orifice and dilatation of the main pancreatic duct were often adenocarcinomas. CONCLUSION: Although follow-up of intraductal hyperplasia is a reasonable approach, other types of IDT and MCT require surgical treatment.

Adenocarcinoma↗

PubMed2000

Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis. Interleukin- 18 (IL-18), for which the gene was recently cloned, is a novel T helper 1 cytokine, which augments interferon-gamma production. We designed this study to clarify the role of IL-18 in primary biliary cirrhosis and to examine whether serum IL-18 level can be a prognostic indicator for the disease. Serum IL-18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus-related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL-18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus-related liver cirrhosis and obstructive jaundice (P < 0.05). The IL-18 levels in primary biliary cirrhosis increased according to the disease progression, and fell promptly after living-related liver transplantation. Moreover, serum IL-18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin-18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.

Autoimmune Diseases↗

PubMed2000

Modified rapid urease test for Helicobacter pylori detection in relation to an immunohistochemical stain.

BACKGROUND: The rapid urease test and touch cytology have been used for the rapid detection of Helicobacter pylori infection. Recently, a modified rapid urease (MRU) test, which provides results in 20 min has been available on a commercial basis. To date, few reports have evaluated the accuracy of this test. This study evaluated the sensitivity, specificity, and accuracy of the MRU test and touch cytology to detect H. pylori in relation to the density of H. pylori infection determined semi-quantitatively by using immunohistochemical stains. METHODS: Biopsy specimens obtained from a total of 60 patients who underwent endoscopy for evaluation of gastroduodenal diseases were studied by using the MRU test, Giemsa stain for touch smear tissue and histological methods. An immunohistochemical stain was used as a standard, and the density of H. pylori infection was graded according to the number of individual bacteria seen as follows: grade 0 = 0; grade 1+ = 1-9; grade 2+ = 10-29; grade 3+ = 30-99; grade 4+ > or = 100. The severity of gastritis was evaluated histologically in each specimen and compared with the density of H. pylori infection. RESULTS: The MRU test had an overall sensitivity of 73%, specificity of 100% and accuracy of 85%. The Giemsa stain had a sensitivity of 91%, specificity of 100% and accuracy of 95%.The sensitivities of the MRU test and Giemsa stain decreased in mild H. pylori infection. In the MRU test, the sensitivity was 47% when the density of H. pylori infection was 1+, while 80-100% sensitivities were obtained when the densities of infection were > or = 2+. With the Giemsa stain, the sensitivity was 80% when the density was 1+, while the sensitivity increased to 100% when the densities were > or = 2+. The severity of gastritis determined by the Rauws scores showed a positive correlation with the density of H. pylori infection as evaluated by immunohistochemical staining. CONCLUSIONS: The MRU test had high sensitivity and specificity for moderate to severe H. pylori infection, but it may result in false-negative results in tests for mild infection. As the MRU test has the advantages of shorter incubation times and low cost, a combination of the MRU test and the Giemsa stain for touch cytology may be the most time- and cost-efficient tests in a clinical setting for the diagnosis of H. pylori infection.

Cytodiagnosis↗

PubMed2000

Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.

BACKGROUND: Acute graft-versus-host disease still represents the major factor that limits successful allogeneic bone marrow transplantation. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease. OBJECTIVE: This study was performed to investigate whether the serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were associated with the manifestation of acute graft-versus-host disease. METHODS: Serum cytokine levels were measured by sandwich ELISA in 18 patients who underwent allogeneic bone marrow transplantation. RESULTS: Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were increased in patients in whom acute graft-versus-host disease developed. However, only serum soluble IL-2 receptor levels were significantly related to disease severity. Serum levels of IL-12 and IL-18, both of which are mainly produced by activated macrophages, were increased in different phases of acute graft-versus-host disease, especially grade I. Serum levels of soluble IL-2 receptor and IFN-gamma were significantly elevated in patients with fever. CONCLUSION: Serum levels of soluble IL-2 receptor were more closely related to the severity of acute graft-versus-host disease than those of IL-12, IL-18, and IFN-gamma.

Acute Disease↗