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[Mercaptoacetyltriglycine (MAG 3) 99mTc--a new radiopharmaceutic for uropoietic diagnoses].

The present authors show mercaptoacetyltrigylcine (MAG 3), labelled with 99mTc technetium, as a novel prospective diagnostic agent of the uropoietic system, replacing the injections of sodium iodohippurate labelled with 131I. The paper reports the procedure of labelling of this novel radiopharmaceutical with technetium 99mTc, evaluation of its quality by chromatographic methods, and biological distribution of MAG 3 in laboratory animals in comparison with the biodistribution of injections of sodium iodohippurate labelled with 131I.

Animals↗

Heterogeneity of human anti-MAG IgM as revealed by their reactivity on avian embryonic tissues.

Monoclonal IgM from patients with peripheral neuropathies frequently have an antibody activity directed against myelin-associated glycoprotein (MAG). Reactivity of 19 of these sera with avian embryonic tissues was compared. Immunohistological studies allowed their classification into distinct groups according to the staining pattern. Both neural and non-neural cell lineages were recognized by these antibodies. The IgM specificities were also compared with those of the monoclonal antibodies HNK-1 and NC-1, which react with MAG and some cell adhesion molecules. Only one group displayed a pattern of staining similar to that observed with these monoclonals. The reactivity of these IgM paraproteins with two cell adhesion molecules, neural cell adhesion molecule and neuron-glia-cell adhesion molecule by immunoblotting confirmed the heterogeneity found in the histological study.

Animals↗

[Polyneuropathies and gammapathies: a form with antiglycoprotein MAG antibodies].

Two cases of polyneuropathy with IgM gammopathy are reported. Myelin associated glycoprotein is the antigen for the monoclonal antibody in both of these patients. The same antigenic specificity has now been identified in other patients having a paraproteinemia with a polyneuropathy. These findings suggest the existence of a new syndrome characterized by: a) a primary demyelinating neuropathy; b) a monoclonal IgM antibody to a specific glycoprotein component of myelin, referred to as myelin associated glycoprotein (MAG). As in other humorally mediated autoimmune diseases, it is suggested that demyelination is caused by circulating anti-MAG antibodies. The role of immunosuppressive drugs and plasmapheresis is discussed.

Aged↗

Evaluation of mag-fura-5, the new fluorescent indicator for free magnesium measurements.

The new fluorescent indicator, mag-fura-5, was evaluated for its ability to measure accurately physiological changes in cytosolic free magnesium. The apparent dissociation constants (Kd) of the fluorochrome for Mg2+, Mg2+/EGTA and Ca2+/EGTA solutions were 14.7 mM, 15.4 mM, and 1.8 mM respectively. The calculated difference in the fluorescence ratios and in the resulting pMg between the standards with low-Ca2+ or low H+ backgrounds and the corresponding samples with approximately physiological levels were not significant. In contrast, the changes due to an increased Ca2+ or H+ content were statistically significant, with mean pMg differences of 0.10 +/- 0.09 (P < 0.02) and 0.33 +/- 0.26 (P < 0.01) respectively. Repetitive measurements on 3 consecutive days yielded comparable data with differences not exceeding 4%. Because of the good reproducibility, it is suggested that the new fluorescent probe may be suitable for free cytosolic magnesium determinations in isolated cells.

Calcium↗

A large renal pelvic diverticulum, presenting incomplete excretion during tc-99m MAG-3 scintigraphy and tracer accumulation on tc-99m DMSA scintigraphy; a case report.

This case report illustrates the dynamic and static renal scintigraphic images of a patient with an unusual large diverticulum of the renal pelvis. The initial diagnosis by intravenous pyelography (IVP) and ultrasonographic (US) examination was a renal pelvic diverticulum of the left kidney, and the patient was referred to the nuclear medicine department for exploration of the effect of the pelvic diverticulum on renal functions. We performed dynamic renal scintigraphy with technetium-99m (Tc-99m) labeled mercaptoacetyl triglycine (MAG-3) and static renal scintigraphy with Tc-99m labeled dimercaptosuccinic acid (DMSA). In dynamic renal scintigraphy, bilaterally normal concentration function was observed. While right kidney excretion function was normal, an incomplete excretion pattern was seen on the left side. Complete urinary flow obstruction occurred approximately at the 10th minute of the acquisition, which did not seem to respond to the i.v. furosemide application. However, when only the renal cortex was included in the region of interest, the obstructive pattern disappeared. In static renal scintigraphy, a large renal pelvic diverticulum localized antero-medially was clearly visualized in the left-anterior oblique projection, most probably due to accumulation of radiopharmaceutical inside it. This case showed that a renal pelvic diverticulum should be thought of when an incomplete excretion pattern is seen on dynamic renal scintigraphy. Using only a cortical region of interest may also help to distinguish other types of obstructive pattern from diverticulum. Additionally, Tc-99m DMSA scintigraphy may show diverticulum localization with antero-oblique projections in addition to routine projections.

Adult↗

Antibodies to sulfated glucuronic acid containing glycosphingolipids in neuropathy associated with anti-MAG antibodies and in normal subjects.

Serum of patients with neuropathy and IgM monoclonal antibodies (M-proteins) that bind to the myelin-associated glycoprotein (MAG) were tested for binding to the major cross-reactive sulfated glucuronic acid containing glycosphingolipid, sulfated glucuronic acid paragloboside (SGPG). IgM binding to the glycolipid was detectable at serum dilutions of 1:10,000 and reactivity was greatest at 4 degrees C. Low titers of IgM binding to the glycolipid were also detected in sera from normal subjects and from patients with neurologic or rheumatologic diseases without serum M-proteins. Binding activity was present in 25% of the sera tested, and titers ranged between 1:25 and 1:400. One patient with peripheral neuropathy, however, had a measurable titer of 1:12,800 in the absence of monoclonal gammopathy. The study indicates that cold reacting anti-SGPG IgM antibodies are frequent constituents of the normal human antibody repertoire, and that monoclonal or polyclonal expansion of B cells that secrete these antibodies, is associated with peripheral neuropathy.

Antibodies, Monoclonal↗

MAG, a novel plasma protein receptor from Streptococcus dysgalactiae.

The gene encoding a plasma protein receptor from Streptococcus dysgalactiae has been cloned and sequenced. The gene product, with a predicted molecular mass of approx. 44 kDa, binds alpha 2-macroglobulin (alpha 2 M), serum albumin and immunoglobulin G (IgG). By subcloning and expressing various parts of the gene as fusion proteins, we found that the three binding activities reside in discrete domains of the protein. The single IgG-binding domain, localized in the C-terminal part of the molecule, shows high homology to streptococcal type-III Fc receptors. In the middle of the molecule, there is a stretch of 50 amino acids (aa) mediating albumin binding. This region has partial homology with the albumin-binding domains of streptococcal protein G. The alpha 2 M-binding domain is located in the N terminus of the molecule and is composed of a unique aa sequence. We call this trifunctional plasma protein receptor, MAG (binds alpha 2 M, albumin and IgG).

Albumins↗

Characterization of Mg2+ transport in brush border membrane vesicles of rabbit ileum studied with mag-fura-2.

Mg2+ transport in rabbit ileal brush border membrane vesicles (BBMV) was characterized by means of a modified mag-fura-2 technique. In the presence of an i>o Na+ gradient, BBMV showed a saturable Mg2+ uptake with a Km of 1.64 mmol l-1. There was no evidence of an overshoot. K+, Li+, and choline+ were as effective as Na+ in stimulating Mg2+ transport. In contrast, only a small amount of Mg2+ transport was observed in the presence either of an o>i Na+ gradient, or in an Na+ equilibrium or in the absence of Na+. Moreover, the findings that Na+ efflux was not stimulated but inhibited by outside Mg2+ and that the nonfluorescent amiloride-analogues DMA and EIPA did not affect Mg2+ transport do not favour the idea of an Mg2+/Na+ antiport system. At Cl- equilibrium, independent of the Na+ gradient, the rate of Mg2+ transport was markedly suppressed compared with the transport rate noted in the presence of an i>o Cl- gradient. The stimulating effect of inside anions could be enhanced by SCN- and decreased by SO2-4. Furthermore, nonfluorescent anion transport antagonist H2-DIDS stimulated Mg2+ transport. These findings indicate that Mg2+ transport can be modulated by inside anions. Mg2+ transport appeared to be electroneutral because it was not dependent on membrane potential. Mg2+ transport was neither stimulated by Bay K8644, a Ca2+ channel agonist, nor inhibited by verapamil, diltiazem, nifedipine and imipramine, the Ca2+ channel antagonists. It, therefore, seems unlikely that Mg2+ uses the Ca2+ transport system.

Animals↗

High-performance liquid chromatographic analysis for the determination of a novel polymer-bound camptothecin derivative (MAG-camptothecin) and free camptothecin in human plasma.

A selective HPLC assay is described for the determination of free and total (free plus polymer-bound) camptothecin (CPT) in human plasma after administration of the anti-tumor drug MAG-CPT (polymer bound camptothecin). Total CPT levels were determined after hydrolysis and free CPT was extracted from acidified plasma using Oasis solid-phase extraction material. Extracts were analyzed on a Zorbax SB-C8 analytical column, using a mixture of acetonitrile-25 mM phosphate buffer (pH 4.0) as the eluent. Detection was performed fluorimetrically. Concentrations of polymer-bound CPT were calculated by subtraction of free from total CPT. The lower limits of quantitation of the methods were 100 ng/ml for total and 1.0 ng/ml for free CPT using 50 microl and 250 microl plasma, respectively. Special attention was paid to the stability of the analytes. The presented method was successfully applied in a clinical pharmacokinetic study in our institute.

Antineoplastic Agents, Phytogenic↗

Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro.

Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibition by MAG and by myelin in general. While MAG/myelin support the growth of young DRG neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are high in young DRGs but drop spontaneously at an age that coincides with the switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury.

Animals↗

P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp.

In inhibiting neurite outgrowth, several myelin components, including the extracellular domain of Nogo-A (Nogo-66), oligodendrocyte myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG), exert their effects through the same Nogo receptor (NgR). The glycosyl phosphatidylinositol (GPI)-anchored nature of NgR indicates the requirement for additional transmembrane protein(s) to transduce the inhibitory signals into the interior of responding neurons. Here, we demonstrate that p75, a transmembrane protein known to be a receptor for the neurotrophin family of growth factors, specifically interacts with NgR. p75 is required for NgR-mediated signalling, as neurons from p75 knockout mice are no longer responsive to myelin and to each of the known NgR ligands. Blocking the p75-NgR interaction also reduces the activities of these inhibitors. Moreover, a truncated p75 protein lacking the intracellular domain, when overexpressed in primary neurons, attenuates the same set of inhibitory activities, suggesting that p75 is a signal transducer of the NgR-p75 receptor complex. Thus, interfering with p75 and its downstream signalling pathways may allow lesioned axons to overcome most of the inhibitory activities associated with central nervous system myelin.

Animals↗

Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13.1-13.3 in a large consanguineous Lebanese family: exclusion of MAG as a candidate gene.

Autosomal recessive Charcot-Marie-Tooth disease (CMT) type 4 (CMT4) is a complex group of demyelinating hereditary motor and sensory neuropathies presenting genetic heterogeneity. Five different subtypes that correspond to six different chromosomal locations have been described. We hereby report a large inbred Lebanese family affected with autosomal recessive CMT4, in whom we have excluded linkage to the already-known loci. The results of a genomewide search demonstrated linkage to a locus on chromosome 19q13.1-13.3, over an 8.5-cM interval between markers D19S220 and D19S412. A maximum pairwise LOD score of 5.37 for marker D19S420, at recombination fraction [theta].00, and a multipoint LOD score of 10.3 for marker D19S881, at straight theta = .00, strongly supported linkage to this locus. Clinical features and the results of histopathologic studies confirm that the disease affecting this family constitutes a previously unknown demyelinating autosomal recessive CMT subtype known as "CMT4F." The myelin-associated glycoprotein (MAG) gene, located on 19q13.1 and specifically expressed in the CNS and the peripheral nervous system, was ruled out as being the gene responsible for this form of CMT.

Adolescent↗

StrainMake: reproducible hybrid metagenomics with MAG recovery and strain-level resolution.

SUMMARY: Metagenomic workflows involve complex multi-step analyses, from quality control and assembly to binning, annotation, and strain-level profiling. Few existing metagenomic pipelines achieve the combination of flexibility, reproducibility, and hybrid assembly support within a unified workflow. We present StrainMake, a Snakemake-based workflow for de novo metagenomic analysis from short, long, or hybrid sequencing data. StrainMake integrates widely used tools across all major steps-quality control, assembly, binning, dereplication, taxonomic and functional annotation-while also providing non-redundant gene catalogues, community-scale metabolic models, and strain-level microdiversity metrics. The modular design enables the use of alternative tools, scalable execution on HPC systems, and full reproducibility through Snakemake and Conda. RESULTS: Applied to the CAMI II strain-madness dataset, StrainMake produced high-quality assemblies and metagenome-assembled genomes (MAGs), while enabling strain-resolved comparisons across samples. Hybrid assemblies improved contiguity, whereas short-read assemblies offered faster runtimes, illustrating the workflow's benchmarking capacity. AVAILABILITY AND IMPLEMENTATION: StrainMake is open source and available at https://github.com/UMMISCO/strainmake, together with comprehensive documentation. Generated data are deposited in Zenodo (doi: 10.5281/zenodo.16950162).

Metagenomics↗

Methodological and interpretive constraints resulting from the use of the Per-Mag classification in high-risk information-processing research.

It has previously been argued that the current Per-Mag classification criteria may erroneously select some individuals who are not vulnerable to psychosis. We suggest that a second false-positive problem exists with these criteria. Specifically, actively psychotic individuals may be included in presumably prepsychotic samples. Implications of this problem for at-risk information-processing research are discussed.

Humans↗

The new HMI beamline MAGS: an instrument for hard X-ray diffraction at BESSY.

The Hahn-Meitner-Institute Berlin is operating the new hard X-ray diffraction beamline MAGS at the Berlin synchrotron radiation source BESSY. The beamline is intended to complement the existing neutron instrumentation at the Berlin Neutron Scattering Centre. The new beamline uses a 7 T multipole wiggler to produce photon fluxes in the 10(11)-10(12) photons s(-1) (100 mA)(-1) (0.1% bandwidth)(-1) range at energies from 4 to 30 keV at the experiment. It has active bendable optics to provide flexible horizontal and vertical focusing and to compensate the large heat load from the wiggler source. The experimental end-station consists of a six-circle Huber diffractometer which can be used with an additional (polarization) analyser and different sample environments. The beamline is intended for single-crystal diffraction and resonant magnetic scattering experiments for the study of ordering phenomena, phase transitions and materials science.

Equipment Design↗

Normal-appearing captopril MAG-3 renal scintigraphy in hemodynamically significant renal artery stenosis. A case report.

The finding from a normal-appearing angiotensin converting enzyme (ACE)-inhibitor renal scan is generally reassuring to the physician screening for renovascular hypertension. In fact, the false-negative rate for captopril scintigraphy is very low. Possible reasons for false-negative scans have not been well documented. A fifty-two-year-old man was evaluated and found to have renovascular hypertension on two occasions, at initial presentation and again eight months later (restenosis had occurred). Renovascular hypertension was present on both occasions as judged by decline of blood pressure following angioplasty of right renal artery stenosis (approximately 80% and approximately 70% stenosis on the two occasions, respectively). However, ACE-inhibitor renal scanning with 99mTc MAG-3 gave disparate results on the two occasions. The first study using oral captopril (25 mg) indicated a low probability of renal artery stenosis, whereas the second study done with the patient regularly taking lisinopril (10 mg daily) was markedly positive. Possible reasons for the initial negative study include poor absorption of oral captopril or inadequate inhibition of the renin-angiotensin system by the 25 mg dose.

Captopril↗

Distribution of sodium and potassium channels as well as myelin associated glycoprotein (MAG) during the early stages of Wallerian degeneration.

The distribution of sodium and potassium channel proteins and the myelin associated glycoprotein (MAG) was studied by immunofluorescence during the early stages of Wallerian degeneration. Routine electron microscopy was also performed in order to investigate the success of the lesion in producing degeneration and also to evaluate the integrity of the axolemma and cytoskeleton. Sural nerves from Sprague-Dawley rats were submitted to surgical crush and analyzed after 30, 36 and 48 h. The preparations were observed by light microscopy and the amount of labeled and unlabeled sites was quantified using a computer linked microscope. The number of sodium and potassium labeled nodes was dramatically reduced 30 h after crushing. However, a small number of labeled nodes was still present even after 48 h. These remaining nodal channel proteins are probably responsible for the maintenance of the nerve's electrical activity during the first 4 days of Wallerian degeneration. Ultrastructural analyses of longitudinal sections revealed areas of intact axolemma in the presence of a partially or completely disrupted cytoskeleton. These results are in disagreement with the generally accepted view that axolemma and cytoskeleton disruption occur simultaneously in the peripheral nervous system. Our results also concern the mechanism underlying the disappearance of these channel proteins during the degeneration of the peripheral nerve fibres, since in this pathology the axons are affected before myelin and Schwann cells become affected.

Animals↗