Methylmalonic aciduria in pregnancy: a case report

Methylmalonic aciduria is a rare metabolic disorder of amino acid metabolism that is characterized by accumulation of large amounts of methylmalonic acid in the blood and urine. To our knowledge this is the first case report of a patient with methylmalonic aciduria who carried a pregnancy to term; the outcome was favorable despite high levels of methylmalonic acid in the serum and urine.     

Nanoparticle detachment: a possible link between macro- and nanotribology?

Although particle detachment is a common phenomenon associated with most tribological processes, it seldom occurs that each piece of elemental debris can be considered as the result of a single event. Such an association has been revealed by the systematic study of a specific system, where a pin of graphite is made to rub against thoroughly polished steel. While the discontinuous nature of the transfer film allows a quantitative assessment of the volume of transfer h _e to be made by 3D optical-profilometry, the linear dependence of the rate of particle detachment dh _e/dn (n=number of rubbing cycles) with the logarithm of sliding speed v strongly suggests the existence of a particular type of stick–slip, where each stick may lead to the detachment of a debris particle. The variations in size of these debris with environment as revealed by AFM, further suggest that the global rate of particle detachment is of the form: dh _e/dn=Nx _i , where N is the number of stick–slip events per rubbing cycle, x the proportion of stick events leading to a cohesive rupture, and _i the mean volume of an elemental particle. While this relation is apparently supported by most experimental results, its actual validation can only be made by experiments at the level of single (nanoscale) asperities, carried out under well-controlled experimental conditions.     

Expression and localization in the fish retina of a homologue of the Alzheimer's related PS1 gene

Early-onset familial Alzheimer's disease (early-onset FAD) has been linked with mutations in the presenilin gene, PS1. Mutations in PS1 may affect the processing/trafficking of b-amyloid precursor-protein (bAPP) and favour the production of toxic amyloid-b fragments that are associated with neural degeneration. This study reports the expression of a PS1-like cDNA in the carp (Cyprinus carpio) retina (the encoded protein shows 76% identity to the human PS1 protein). Carp PS1 mRNA was localized by in situ hybridization to the photoreceptor cell, inner nuclear and ganglion cell layers. Expression of the PS1 gene in the rat retina was also confirmed. The retinal expression of PS1 raises the possibility that PS1 mutations also lead to neural degeneration in the retina.     

Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion

Indirect antigenic stimulation by H. pylori-specific T cells is implicated in the development of low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT), however, the role of direct antigen stimulation is unknown. To study the role of direct antigen stimulation in MALT lymphomagenesis and its relationship with the pathogenesis of distinct pathological lesions, which represent different stages of the tumour progression, we cloned and sequenced the rearranged immunoglobulin (Ig) heavy chain gene in three low-grade (two from the lung, one from the stomach) and one high-grade (from the stomach) cases. In the low-grade gastric case, we studied the Ig sequence in primary as well as its disseminated and recurrent tumours. In the high-grade gastric case, we analysed the Ig sequence in tumour cell populations microdissected from the residual diffuse low-grade lesions, diffuse high-grade areas from follicles colonized by high-grade blasts. Compared with the published germline sequences, the heavy chain variable (VH) genes of three MALT lymphomas, in which the putative germline was identified, contained frequent somatic mutations, showing a much higher ratio of replacement/silent mutations in the complementarity determining regions (CDRs) than the framework regions (FRs). Ongoing mutation as indicated by intraclonal variation of the Ig sequence clearly existed in low-grade tumour including its dissemination and recurrence, but was not evident in high-grade tumour cell populations including those microdissected from independent colonized follicles. In addition, the germlines of VH genes used by the three MALT lymphomas are frequently found in autoreactive antibodies. Our results suggest that MALT lymphoma derives from postgerminal centre memory B cells, possibly autoreactive B cell clones, and that direct antigen stimulation may play an important role in the clonal expansion of low-grade MALT lymphoma.     

Die kombinierten Desoxidationsgleichgewichte mit Mangan,Aluminium und Silicium sowie ihre Bedeutung für die Einschlußbildung

Thermodynamische Berechnung des Zustandsschaubildes MnO–Al₂O₃. Polytherme Darstellung des Schlackensystems FeO_n–MnO–Al₂O₃. Entwicklung der kombinierten Desoxidationsgleichgewichte mit Mangan und Aluminium sowie Einschluß-bildung während der Auflösung von Aluminium in einer manganhaltigen Stahlschmelze. Entwicklung der kombinierten Desoxidationsgleichgewichte mit Aluminium und Silicium. Einfluß von Mangan auf die kombinierten Desoxidationsgleichgewichte mit Aluminium und Silicium.     

Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone

The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.     

True histiocytic lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases

We describe the morphologic, immunohistologic, and genotypic characteristics of 13 cases of true histiocytic lymphomas. Six cases presented with primary gastrointestinal involvement, five with lymphadenopathy, the other sites involved being the bone marrow and the skin. The neoplastic cells displayed large abundant eosinophilic cytoplasm, occasionally vacuolated with folded or bizarre-shaped nuclei with prominent nucleoli. Mitotic figures were numerous. Multinucleated cells were common. The pattern of growth was usually diffuse and noncohesive. Spindle cell sarcoma-like areas were evident in five cases, with a prominent foam cell component in four cases. All cases expressed histiocyte-associated markers (CD68, lysozyme, alpha-1-antitrypsin), CD45 or CD45RO, and were negative for CD1a, epithelial, and B- and T-cell lineage-specific markers. Reactivity for S-100 was observed in a variable proportion of cells in 11 cases. The proliferation fraction varied from 3 to 88%. Genotypic analysis for T-cell receptor or immunoglobulin gene rearrangement demonstrated a germline configuration in all cases. We demonstrate that true histiocytic lymphoma is a rare distinctive pathologic entity that may be defined by immunohistochemical criteria and that recognition among histiocytic disorders is important for clinical and prognosis reasons.     

Histologic, molecular, and radiologic characterization of resolving cerebral posttransplant lymphoproliferative disorder

Lymphoproliferative disorders (LPDs) are commoner in pediatric versus adult immunosuppressed transplant recipients, and frequently involve the central nervous system. In these circumstances, the justification for biopsy is heavily influenced by the likely diagnostic yield. The present study centers on a 12-y-old renal transplant patient who developed multifocal cerebral LPD and had serial magnetic resonance (MR) examinations during the course of her illness from which she has completely recovered upon reduction of immunosuppression. She underwent stereotaxic biopsy, which was analyzed by both immunocytochemistry and polymerase chain reaction to examine the general question of how to release the maximum amount of information contained within, as well as to obtain a tissue diagnosis in this particular case. We show that a combination of these methods permits identification of the immunophenotype, lineage, clonality, viral involvement, and origin of abnormal cellular infiltrates. The biopsy also showed a novel histologic pattern of LPD, comprising numerous benign T cells obscuring a tiny clone of B cells. The MR examinations documented, for the first time, the differences in signal that accompany clinical resolution at both biopsied and nonbiopsied sites, showing that the latter may be associated with reduction, but not elimination, of MR signal abnormality. We conclude: 1) a combination of conventional and polymerase chain reaction analysis offers the greatest diagnostic yield from stereotaxic biopsies, even when the available tissue is minimal; 2) a focal polyclonal T cell infiltrate should prompt further investigation to exclude an underlying B cell lesion.     

A comparative study of the value of immunohistochemistry and the polymerase chain reaction in the diagnosis of follicular lymphoma

We have compared the value of immunohistochemical and polymerase chain reaction (PCR) techniques in distinguishing follicular lymphoma from follicular hyperplasia in formalin-fixed paraffin-embedded tissues of 41 follicular lymphomas, 15 reactive lymph nodes and 5 reactive tonsils. Immunohistochemistry demonstrated bcl-2 protein in the follicle centre cells of 97% of follicular lymphomas whereas monoclonal immunoglobulin light chain was detected in 83% of cases. Assessing the lowest proliferating follicle of each case by MIB-1 immunostaining, proliferation fractions in the lymphomas varied from 0.5% to 59% (mean 15.6%). Over 80% of lymphomas had proliferation fractions of less than 25%. PCR detected gene rearrangement either at the bcl-2 locus, or at the IgH locus, or at both loci in 32%, 44% and 61% of lymphomas, respectively. The follicle centre cells of the reactive lymph nodes and tonsils were all bcl-2 protein negative and polytypic for kappa and lambda light chains. Proliferation fractions of the lowest proliferating follicle in each reactive case ranged from 30.5% to 86.8% (mean 64.9%). Rearrangements of the bcl-2 or IgH loci were not detected in any reactive case. This study demonstrates that bcl-2 and light chain immunostaining are the most consistently helpful aids to diagnosing follicular lymphoma. A low proliferation fraction also indicates lymphoma but a high proliferation fraction does not exclude the diagnosis. Immunostaining with a combination of anti bcl-2 and MIB 1 antibodies is a sensitive and specific method for identifying follicular lymphoma, is technically simple to perform and easy to interpret. In occasional cases, where immunostaining gives equivocal results, PCR analysis can confirm lymphoma, but a negative result does not exclude the diagnosis.