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PubMedDate not supplied

alpha 2-Macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease.

Because it has been suggested that alpha 2M could be involved in the generation of amyloid peptide, attention was given to a possible association of alpha 2M expression and amyloid accumulation in the brain. Therefore, we investigated the presence of the proteinase inhibitor alpha 2-macroglobulin (alpha 2M) in the cerebra of 4 patients with Alzheimer's Disease (AD). One case of a patient with Down's syndrome, 2 cases of patients with Dementia of the Lewy Body type (DLB), 1 case of an aged, clinically nondemented person who displayed many amyloid plaques, and 3 normal aged control brains were also studied. The results obtained by immunocytochemistry with monoclonal antibodies directed against two different epitopes of human alpha 2M showed an association of alpha 2M, only with neuritic-type plaques in patients with AD. No alpha 2M immunoreactivity was found in either preamyloid-type plaques or burned out-type plaques in AD, DLB, or aged nondemented controls. The results do not support a direct role of this proteinase inhibitor in the formation of amyloid. Because alpha 2M is observed to be associated with reactive microglia in the outer border of the neuritic plaques, the data suggest that alpha 2M could be a marker for an inflammatory cellular process in these neuritic plaques.

Aged↗

PubMed1985

Early onset myophosphorylase deficiency (Mc Ardle's disease) with absence of myophosphorylase protein on SDS electrophoresis. The role of the ischemic forearm test.

The authors present a case report of early onset myophosphorylase deficiency (Mc Ardle's disease) with absence of myophosphorylase protein on SDS-electrophoresis. The different varieties of myophosphorylase deficiency and the clinical investigations which may lead to the diagnosis are reviewed. In particular, the relevance and possible dangers of an ischemic forearm exercise test and the suggestion of using a needle biopsy as a preliminary screening in similar cases of metabolic myopathies are discussed.

Adult↗

PubMed1992

Purulent meningitis due to aspergillosis in a patient with systemic lupus erythematosus.

We report a 39-year-old female patient with systemic lupus erythematosus under immunosuppressive therapy who developed persistent neutrophilic meningitis, for which no infectious agent could be identified. Intensifying the immunosuppressive therapy induced a short amelioration of the clinical picture. At autopsy, basal meningitis was found to be due to Aspergillus sp.

Adult↗

PubMed1995

Chordoma of the lower cervical spine.

Vertebral chordomas are rather rare tumours, especially in the lower cervical region. We present a patient with a C7 vertebral body chordoma and a discussion of pertinent literature is given. Only three C7 chordomas have been reported previously. Diagnosis is sometimes difficult to establish and is based on radiological examinations. Once the histological diagnosis is available, one should aim at a total resection. If this is not possible, adjuvant radiotherapy should be given. For limited cervical lesions, we advise a corporectomy with fusion by an iliac crest graft and osteosynthetic plate stabilisation.

Cervical Vertebrae↗

PubMed1994

Appearance of localized immunoreactivity for the alpha 4 integrin subunit and for fibronectin in brains from Alzheimer's, Lewy body dementia patients and aged controls.

The localization of alpha 4 integrin subunit and of fibronectin in Alzheimer's disease (AD), Down's syndrome, Lewy body dementia (DLB) and normal brains was immunohistochemically investigated. Antibodies against the alpha 4 subunit and a fibronectin specific antibody stained 'neuritic' plaques in AD and Down's syndrome, while 'preamyloid' and 'burned-out' plaques remained negative. No alpha 4 integrin subunit or fibronectin immunoreactivity was detected in the plaques of DLB consistent with the absence of neuritic plaques. In addition, hippocampal pyramidal neurons and some neocortical neurons showed immunoreactivity with alpha 4 subunit and fibronectin antibodies in all aged individuals, but not in younger controls. These results suggest an age-related and localized expression of alpha 4 integrin subunit and fibronectin in the brain.

Adolescent↗

PubMed1984

The stimulation of prolactin secretion by taurine: studies on the site of action.

Taurine's site of action within the central nervous system was localized by studying its effect on prolactin secretion following the microinfusion of 125 nmoles of this amino acid into discrete regions of the brain. Taurine was found to stimulate prolactin secretion only when microinfused into the arcuate nucleus of the hypothalamus. Taurine was not effective in other areas of the hypothalamus or in several extra-hypothalamic sites. Mannitol infusions (125 nmoles) into the arcuate nucleus, used as a control, were without effect on prolactin secretion. These studies extend previous observations on the prolactin-releasing action of centrally administered taurine and suggest further that the arcuate nucleus is one target site for this action.

Animals↗

PubMed1994

NAD-independent Actinobacillus pleuropneumoniae strains: production of RTX toxins and interactions with porcine phagocytes.

Actinobacillus pleuropneumoniae RTX toxin (Apx) production by A. pleuropneumoniae biotype 2 (NAD-independent) serotype 2 strains was studied. Western blot analysis of culture supernatants of all biotype 2 strains tested revealed the presence of a 103 kDa protein which reacted with a monoclonal antibody against ApxIIA. This protein was also recognized by sera of pigs infected with a biotype 2-serotype 2 strain. Furthermore, antibodies that could neutralize ApxIIA were present in these sera. Proteins corresponding to ApxIA or ApxIIIA were not detected. The effects of a biotype 1-serotype 2 and a biotype 2-serotype 2 strain and their metabolites on the oxidative activity of porcine pulmonary alveolar macrophages (PAM) and polymorphonuclear cells (PMN) were compared using a chemiluminescence (CL) technique. Viable bacteria of both biotypes stimulated the production of oxygen radicals by phagocytes. CL responses were higher for the biotype 1 than for the biotype 2 strain. After having reached a peak value, the oxidative activity decreased until a total inhibition was achieved. Inactivated washed bacteria had no influence on the oxidative activity of phagocytes. In contrast, heat labile factors in culture supernatants of both biotypes stimulated and inhibited the oxidative activity of PAM in a dose-dependent manner. Dilutions of supernatant up to 1/32 of the biotype 2 strain and up to 1/512 of the biotype 1 strain were toxic for PAM, while dilutions from 1/64 to 1/128 of the biotype 2 strain and from 1/1024 to 1/4096 of the biotype 1 strain stimulated the oxidative activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinobacillus pleuropneumoniae↗

PubMedDate not supplied

4-bromo-2,5-dimethoxyamphetamine: psychoactivity, toxic effects and analytical methods.

4-bromo-2,5-dimethoxyamphetamine (bromo-DMA) is a drug of special interest in Australia as it is available in forms which are seldom seen elsewhere in the world. Data of interest to the Forensic Chemist is summarized. The psychoactivity of bromo-DMA is discussed and a number of case histories involving higher doses are related. A description of dosage forms has been included and variations in drug concentration is discussed. Chemical properties and various methods of quantitative and qualitative analysis, including the use of high performance liquid chromatography, mass spectrometry and infra-red spectroscopy are listed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1992

Single photon emission computed tomography using perfusion tracers in seizure disorders.

Single photon emission computed tomography (SPECT) using perfusion tracers makes it possible to estimate regional cerebral blood flow (rCBF) and, indirectly, local brain metabolism. It may be possible to detect and follow physiopathological alterations, such as may be seen in seizure disorders. The authors review the principles of and some data on perfusion SPECT in seizure disorders, stress advantages as well as major drawbacks and add their initial experience with Tc-99m hexamethylpropyleneamine oxime (HMPAO) SPECT in febrile convulsions.

Humans↗

PubMed2005

Differences in impulsivity and sensation seeking between early- and late-onset alcoholics.

The personality traits of impulsivity and sensation seeking have been proposed as important features of early-onset alcoholism. Early-onset (EOA, n=62) and late-onset (LOA, n=68 ) alcoholic inpatients were compared as to the severity of their substance use and related problems, and self-report scales measuring impulsivity (Barratt Impulsiveness Scale, version 11), sensation seeking (Sensation Seeking Scale), and aggressiveness (Buss Durkee Hostility Inventory). The symptom severity of the EOAs' alcohol-use disorder and related problems was higher than that of the LOAs. Furthermore, the EOAs had higher levels of impulsivity, sensation seeking, and aggression relative to the LOAs. The differences in impulsivity remained after an analysis controlling for the effect of aggressiveness. Finally, cigarette smoking was positively correlated with impulsiveness across alcoholic subgroups. Active screening for impulsive traits in treatment-seeking alcohol-abusing populations is recommended to improve treatment planning and prevent early drop-out.

Adult↗

PubMed2026

RNA splicing evidence enables robust classification of BRCA1 exon 18 variants: Results from the ENIGMA consortium.

The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) research consortium conducted a comprehensive study to characterize spliceogenic variants in BRCA1 exon 18. The absence of systematic RNA-based assessment for these variants has led to inconsistent interpretation, limiting accurate classification and management of individuals and their families. The splicing profile of 166 variants was assessed using minigene assays; 32 were additionally analyzed in blood-derived RNA from 51 individuals and 18 in mouse embryonic stem cell (mESC)-based assays to evaluate homology-directed repair (HDR) capacity. mRNA assessment by RT-PCR in blood samples and minigene assays showed a significant positive correlation, with splicing analysis in mESCs displaying highly concordant results. The mESC-based HDR assay showed that the in-frame exon 18 skipping (Δ18) transcript encodes a non-functional protein lacking rescue activity. Linear regression analysis using mESC splicing and functional data indicated that ≥59% of full-length (FL) levels and <34% of Δ18 were associated with benign HDR activity. These thresholds differ from those recommended by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) specifications for applying BP7_strong(RNA): >30% functional transcripts or <70% non-functional transcripts. Incorporation of RNA splicing evidence into variant interpretation increased pathogenic (28.6%-31.7%) and benign (3.7%-24.4%) classifications while reducing likely pathogenic (19.5%-17.7%), uncertain (18.9%-8.5%), and likely benign (29.3%-17.7%) categories. Experimental mRNA profiling impacted the interpretation of 34% of variants and resolved uncertainty in approximately 10% of cases. Exon 18 skipping was less tolerated, indicating that the degree of splice perturbation required to impair BRCA1 function may depend on the nature of the resulting non-functional transcript.

Humans↗

PubMed2004

Multivessel distal sutureless off-pump coronary artery bypass grafting procedure using magnetic connectors.

Proximal anastomotic devices for beating heart coronary artery bypass grafting (CABG) have been developed to avoid ascending aortic manipulation. Distal anastomotic devices may become an extremely useful tool to assist in enabling minimally invasive (robotic) multivessel CABG. As a transition phase toward this ultimate goal we have been using a distal anastomotic device for the left internal mammary artery-left anterior descending artery (LIMA-LAD) anastomosis. In addition we recently performed two off-pump coronary artery bypass procedures that were distally completely sutureless.

Aged↗

PubMed2006

N-glycosylation of human nicastrin is required for interaction with the lectins from the secretory pathway calnexin and ERGIC-53.

The gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin (NCT), APH-1 and PEN-2, is responsible for the intramembranous cleavage of amyloid precursor protein (APP), Notch and several other type I transmembrane proteins. gamma-Secretase cleavage of APP releases the Abeta peptides, which form the amyloid plaques characteristic of Alzheimer's disease brains, and cleavage of Notch releases an intracellular signalling peptide that is critical for numerous developmental processes. NCT, a type I membrane protein, is the only protein within the complex that is glycosylated. The importance of these glycosylation sites is not fully understood. Here, we have observed that NCT N-linked oligosaccharides mediated specific interactions with the secretory pathway lectins calnexin and ERGIC-53. In order to investigate the role played by N-glycosylation, mutation of each site was performed. All hNCT mutants interacted with calnexin and ERGIC-53, indicating that the association was not mediated by any single N-glycosylation site. Moreover, the interaction with ERGIC-53 still occurred in PS1/2 double knockout cells as detected in immunoprecipitation as well as confocal immunofluorescence microscopy studies, which indicated that NCT interacted with ERGIC-53 prior to its association with the active gamma-secretase complex.

Amyloid Precursor Protein Secretases↗

PubMed2004

Presumptive FMRF-amide-like immunoreactive retinopetal fibres in Crocodylus niloticus.

A small contingent of 30-50 of centrifugal visual fibres, showing FMRF-amide-like immunoreactivity, has been identified in C. niloticus; these fibres extend from the chiasmatic region into the retina. They do not take the marginal optic tract, but pass medially to the chiasmatic fascicles, from the preoptic region. The cells of origin of these fibres have not been identified. However, none of the retinopetal neurons of the brainstem [M. Medina, J. Reperant, R. Ward, D. Miceli, Centrifugal visual system of Crocodylus niloticus : a hodological, histochemical and immunocytochemical study, J. Comp. Neurol. 468 (2004) 65-85], labelled by retrograde transport of rhodamine beta-isothiocyanate after intraocular injection of this tracer, show FMRF-amide-like immunoreactivity; neither are any of the FMRF-amide-like immunopositive neurons in the crocodile brain, particularly those of the complex involving the terminal nerve and the septo-preoptic region, labelled by rhodamine after its intraocular injection.

Alligators and Crocodiles↗

PubMed2005

GnRH-immunoreactive centrifugal visual fibers in the Nile crocodile (Crocodylus niloticus).

Thin varicose centrifugal visual fibers, between 30-45 in number and displaying cGnRH-I immunoreactivity, were identified in Crocodylus niloticus. Approximately 80% of these fibers were also FMRF-amide-like immunoreactive. The cGnRH-I fibers extended from the preoptic region to the retina where they appeared to terminate in the external portion of the inner plexiform layer. The location of their neurons of origin could not be determined precisely following the intraocular injection of the retrograde axonal tracer RITC. Nevertheless, the presence of cGnRH-I-immunoreactive neurons exclusively within the complex comprising the terminal nerve and the septo-preoptic region, and of several retinopetal fibers labelled retrogradely with the axonal tracer at the septo-preoptic junction, indicates that the cGnRH-immunoreactive centrifugal visual system originates from within this complex.

Alligators and Crocodiles↗

PubMed2006

Distribution of ganglion cells in the pigeon retina labeled via retrograde transneuronal transport of the fluorescent dye rhodamine beta-isothiocyanate from the telencephalic visual Wulst.

The distribution of retinal ganglion cells (RGCs) providing input to the thalamofugal visual system in the pigeon was studied with an anatomical transneuronal transport technique using the fluorescent dye rhodamine beta-isothiocyanate (RITC). Unilateral injections of RITC made into the telencephalic visual Wulst resulted in the retrograde (1) first-order labeling (FOL) of dorsal thalamic (n. dorsolateralis anterior and n. superficialis parvocellularis: SPC) and brainstem somata as well as (2) second-order labeling of other cell populations within the brain and of retinal ganglion cells in both eyes obtained after transneuronal transfer of the tracer from neurons labeled directly via FOL. The mapping and counting of labeled RGCs in retinal flat-mounts showed that they were mainly distributed within the nasal portion of the retinal yellow field (YF) and that their total numbers were consistently higher (averaging 57%) in the eye contralateral to the tracer injection. Labeled RGCs in the retinal red field (RF) represented 13.4% and 12.0% of total labeled cells in the ipsilateral and contralateral eye, respectively. Moreover, the average densities of labeled cells/mm(2) in the RF and YF were respectively 8.4 and 42.8 (ipsilateral) and 17.9 and 54.0 (contralateral). The preferential distribution of labeled RGCs within the nasal YF supports the notion that the thalamofugal visual system in the lateral-eyed pigeon is mainly concerned with viewing in the lateral visual field. Conversely, the relatively low numbers of labeled RGCs observed within the specialized RF indicate that, unlike the case in frontal-eyed bird species and mammals, this system does not appear to be involved in binocular visual processing.

Animals↗

PubMed2026

The landscape of clonal hematopoiesis of indeterminate potential in long-term breast cancer survivors.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) can confound blood-based genomics and may be shaped by cytotoxic therapy; clarifying its persistence after breast-cancer chemotherapy is relevant for long-term survivorship follow-up. PATIENTS AND METHODS: Buffy-coat whole-exome sequencing was performed in 189 stage I-III breast-cancer survivors with blood collected a median 136.5 months after diagnosis. CHIP was assessed using a prespecified 100-gene hematopoietic-driver compendium and exome-wide interrogation. Clinical associations were assessed with univariable tests and multivariable logistic regression including chemotherapy, radiotherapy, age, smoking and obesity. RESULTS: Within the 100-gene compendium, 54/189 (28.6%) patients harbored ≥1 variant, predominantly missense, with DNMT3A and TET2 predominating and multi-hit cases rare. In multivariable models, chemotherapy was not associated with panel-defined CHIP (OR 0.77; 95% CI 0.40-1.48; p = 0.432). Similarly, age, adjuvant radiotherapy, obesity and smoking status were not significantly associated with panel-defined CHIP. Gene-level comparisons showed no differences by chemotherapy exposure. Exome-wide, 67/189 (35.4%) patients carried ≥1 variant; chemotherapy was not associated with exome-wide variant positivity (OR 0.89; 95% CI 0.48-1.67; p = 0.721), and no locus differed between chemotherapy-exposed and never-exposed women. CONCLUSION: Buffy-coat WES performed in long-term breast cancer survivors shows no cohort-level association between prior chemotherapy and increased CHIP.

Humans↗

PubMed2026

Genetic overlap between depression and C-reactive protein levels: Evidence from a cross-trait analysis.

Inflammation and depression have been consistently associated, with elevated C-reactive protein (CRP) levels observed in a significant subset of affected individuals. However, the genetic mechanisms underlying this association remain poorly understood. We integrated results from large-scale genome-wide association studies (GWAS) of depression and CRP levels in a cross-trait analysis specifically focusing on identifying horizontally pleiotropic loci. Identified variants were stratified as concordant versus discordant based on their direction of effects on the two traits and followed up using functional annotation, gene set enrichment, and colocalization analyses. We also explored causal relationships using Mendelian Randomization (MR) analysis with extensive sensitivity analyses, including adjustment for body mass index (BMI). We identified 9 novel loci. Functional analyses revealed that concordant loci were enriched in genes linked to immune and inflammatory processes, while discordant loci mostly mapped to metabolic pathways, including lipid regulation. MR provided strong evidence for body mass index driving a causal relationship between the genetic liability of depression on CRP levels. Our findings suggest that the association between depression and CRP levels is partly driven by shared genetic influences, pointing to different biological pathways depending on whether genetic effects are concordant or discordant. These results underscore the importance of considering effect direction when assessing the genetic overlap between depression and inflammatory processes. In addition, they highlight BMI as a key factor in the causal relationship between depression and systemic inflammation.

C-Reactive Protein↗