scholarly journals A Hallervorden–Spatz-eponímától a molekuláris nevezéktanig

2017 ◽  
Vol 158 (43) ◽  
pp. 1723-1727 ◽  
Author(s):  
Ferenc Garzuly
Keyword(s):  
Political System ◽  
Mitochondrial Protein ◽  
Underlying Disease ◽  
Genetic Alterations ◽  
Brain Iron ◽  
Mentally Disabled ◽  
Professional Activities ◽  
Disease Entities ◽  
Niemann Pick ◽  
Nazi Euthanasia

Abstract: Introduction and aim: A combination of Niemann-Pick- and Hallervorden-Spatz diseases led to the death of a 17-year-old boy in 1994. Genetic counseling necessitated further investigations in 2017. Meanwhile, the nomenclature of Hallervorden-Spatz disease has been abandoned. The author analyze the reasons for this change. Method: Professional activities of Hallervorden and Spatz during and after the Nazi euthanasia program are presented. Also, the scientific efforts that led to the discovery of the genetic background of the disease and ultimately to its new name are highlighted. Results: In nazi Germany, a large number of mentally disabled were killed. The majority of pediatric-brains were transferred to the “Kaiser Wilhelm Institut für Hirnforschung”, led by Hugo Spatz, and was included in the “Hallervorden collection”. Investigations exploring the connections between eponyms and nazi-activites started in the mid-1980s. This process was accelerated by the discovery of genetic alterations underlying disease entities, including neurodegeneration with brain iron accumulation (NBIA). NBIA has several subtypes, with the first being the disease described by Hallervorden and Spatz, and recently renamed to pantothenate kinase-associated neurodegeneration (PKAN). The case examined by the authors belongs to the third subtype, to the mitochondrial protein-associated neurodegeneration (MPAN). Conclusion: The works of the two noted neuropathologists strongly conflict with current ethical principles of human research studies. The buried “Hallervorden collection” in the Munich Waldfriedhof cemetery, and the memorial column erected there will remain a sad reminder of a time when a political system profoundly distorted the judgement of even academic physicians. Orv Hetil. 2017; 158(43): 1723–1727.

scholarly journals The role of macrophages in interstitial lung diseases

2017 ◽  
Vol 26 (145) ◽  
pp. 170009 ◽  
Author(s):  
Giulio Rossi ◽  
Alberto Cavazza ◽  
Paolo Spagnolo ◽  
Salvatore Bellafiore ◽  
Elisabetta Kuhn ◽  
...  
Keyword(s):  
Lung Biopsy ◽  
Morphological Characteristics ◽  
Underlying Disease ◽  
Interstitial Lung Diseases ◽  
Alveolar Haemorrhage ◽  
Routine Practice ◽  
Lipoid Pneumonia ◽  
Diffuse Panbronchiolitis ◽  
Niemann Pick Disease ◽  
Niemann Pick

The finding of collections of macrophages/histiocytes in lung biopsy and bronchoalveolar lavage is relatively common in routine practice. This morphological feature in itself is pathological, but the exact clinical significance and underlying disease should be evaluated together with clinical data, functional respiratory and laboratory tests and imaging studies.Morphological characteristics of macrophages and their distribution along the different pulmonary structures should be examined carefully by pathologists. Indeed, haemosiderin-laden macrophages are associated with smoking-related diseases when pigment is fine and distribution is bronchiolocentric, while alveolar haemorrhage or pneumoconiosis are the main concerns when pigment is chunky or coarse and the macrophages show an intra-alveolar or perilymphatic location, respectively. In the same way, pulmonary accumulation of macrophages with foamy cytoplasm is generally associated with pathologies leading to broncho-bronchiolar obstruction (e.g.diffuse panbronchiolitis, hypersensitivity pneumonia or cryptogenic organising pneumonia) or alternatively to exogenous lipoid pneumonia, some drug toxicity (e.g.amiodarone exposure or toxicity) and metabolic disorders (e.g.type B Niemann–Pick disease).This pathology-based perspectives article is aimed at concisely describing the diagnostic possibilities when faced with collection of macrophages in lung biopsy and cytology.

scholarly journals Classification of renal cell tumors – current concepts and use of ancillary tests: recommendations of the Brazilian Society of Pathology

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Daniel Abensur Athanazio ◽  
Luciana Schultz Amorim ◽  
Isabela Werneck da Cunha ◽  
Katia Ramos Moreira Leite ◽  
Alexandre Rolim da Paz ◽  
...  
Keyword(s):  
Renal Cell ◽  
Who Classification ◽  
Recent Literature ◽  
Underlying Disease ◽  
Genetic Alterations ◽  
Renal Tumors ◽  
Specific Gene ◽  
Brazilian Society ◽  
Resource Limited

AbstractClassification of renal cell carcinomas has become more challenging. The 2016 WHO classification included 14 different subtypes and 4 emerging/provisional entities, and recent literature indicates new entities to be incorporated. Nomenclature is based on cytoplasmic appearance, architecture, combination of morphologies, anatomic location, underlying disease, familial syndromes, and specific genetic alterations. Immunohistochemistry is useful in selected cases while it can be insufficient in entities that require molecular confirmation of a specific gene alteration. The aim of these recommendations is to provide a reasonable and optimized approach for the use of ancillary tests in subtyping renal tumors, particularly in resource-limited settings.

scholarly journals Bridging Molecular Genetics and Biomarkers in Lewy Body and Related Disorders

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Gilbert J. Ho ◽  
Willie Liang ◽  
Masaaki Waragai ◽  
Kazunari Sekiyama ◽  
Eliezer Masliah ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Biological Fluids ◽  
Lewy Bodies ◽  
Underlying Disease ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Common Disease ◽  
Disease Mechanisms

Recent advances have been made in defining the genetic and molecular basis of dementia with Lewy bodies (DLBs) and related neurodegenerative disorders such as Parkinson's disease (PD) and Parkinson's disease dementia (PDD) which comprise the spectrum of “Lewy body disorders” (LBDs). The genetic alterations and underlying disease mechanisms in the LBD overlap substantially, suggesting common disease mechanisms. As with the other neurodegenerative dementias, early diagnosis in LBD or even identification prior to symptom onset is key to developing effective therapeutic strategies, but this is dependent upon the development of robust, specific, and sensitive biomarkers as diagnostic tools and therapeutic endpoints. Recently identified mutations in the synucleins and other relevant genes in PD and DLB as well as related biomolecular pathways suggest candidate markers from biological fluids and imaging modalities that reflect the underlying disease mechanisms. In this context, several promising biomarkers for the LBD have already been identified and examined, while other intriguing possible candidates have recently emerged. Challenges remain in defining their correlation with pathological processes and their ability to detect DLB and related disorders, and perhaps a combined array of biomarkers may be needed to distinguish various LBDs.

scholarly journals Infectious Complications Associated with Monoclonal Antibodies and Related Small Molecules

2009 ◽  
Vol 22 (2) ◽  
pp. 274-290 ◽  
Author(s):  
Edsel Maurice T. Salvana ◽  
Robert A. Salata
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecules ◽  
Disease Process ◽  
Direct Consequence ◽  
Underlying Disease ◽  
Infectious Complications ◽  
Full Potential ◽  
Specific Therapy ◽  
Effect Of Therapy ◽  
Disease Entities

SUMMARY Biologics are increasingly becoming part of routine disease management. As more agents are developed, the challenge of keeping track of indications and side effects is growing. While biologics represent a milestone in targeted and specific therapy, they are not without drawbacks, and the judicious use of these “magic bullets” is essential if their full potential is to be realized. Infectious complications in particular are not an uncommon side effect of therapy, whether as a direct consequence of the agent or because of the underlying disease process. With this in mind, we have reviewed and summarized the risks of infection and the infectious disease-related complications for all FDA-approved monoclonal antibodies and some related small molecules, and we discuss the probable mechanisms involved in immunosuppression as well as recommendations for prophylaxis and treatment of specific disease entities.

On the Differential Diagnosis of Manie - Depressive Insanity and Dementia Præcox. (Glasg. Med. Journ., vol. lxxx., Sept. 1913, pp. 185–192)

1916 ◽  
Vol 62 (258) ◽  
pp. 622-624
Author(s):  
Hubert J. Norman
Keyword(s):  
Mental Disorder ◽  
Underlying Disease ◽  
Dementia Praecox ◽  
Disease Category ◽  
General Acceptance ◽  
Manic Depressive ◽  
Disease Entities ◽  
The Individual ◽  
The Brain ◽  
Organic Change

“The terms manic-depressive insanity and dementia præcox were used by Kraepelin to designate two disease entities, which he considered were between them responsible for most of the states of mental disorder usually gathered together under the title, the psychoses.” The psychoses are something more than states of mental disorder, and something less than disease entities; they lie between them. Excitement, depression, delirium, and stupor are states of mental disorder which may arise during the course of many diseases, general paralysis, hysteria, epilepsy, the cerebropathies, constitutional and infectious diseases; but acute mania, acute melancholia, anergic stupor, delirious mania, are psychoses. They differ from a state of mental disorder in so far as they are self-sufficient, and are not the expression of an underlying disease; moreover, they run a fairly definite course, ending either in recovery or in dementia. The classifications of the psychoses have been unsatisfactory, and none of them has met with general acceptance. The most satisfactory method is that formulated by Kraepelin: and, in the opinion of Dr. Marshall, he “has done for the psychoses what Erb did for the amyotrophies.” He emphasised the importance of dementia as a termination of the psychoses, and gathered those which ended in dementia into one disease category, dementia præcox, and those which did not so end into another category, manic-depressive insanity. The fact that dementia occurred predicated an organic change in the brain, so that dementia præcox was an organic and manic-depressive a functional disease of the brain. Certain states of mental disorder are common to both conditions: yet there are symptoms which render it possible to distinguish between them. In dementia præcox there is “inco-ordination of the individual psychical processes”: manic-depressive insanity depends on “a change in the mutability of the individual psychical processes.” Normal mentality results from the co-ordinated action of the emotional, intellectual, and volitional processes, and is characterised by a certain congruity of thought and conduct. If there is inco-ordination of these fundamental processes, incongruity of thought and conduct results. The nature of the incongruity depends on the mental process mainly responsible for the incoordination. The symptoms may be for a time emotional, intellectual, or volitional.

scholarly journals Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Chary López-Pedrera ◽  
Carlos Pérez-Sánchez ◽  
Manuel Ramos-Casals ◽  
Monica Santos-Gonzalez ◽  
Antonio Rodriguez-Ariza ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Disease Risk ◽  
Underlying Disease ◽  
Systemic Autoimmune Diseases ◽  
New Genes ◽  
Gene And Protein Expression ◽  
New Directions ◽  
Disease Entities ◽  
Traditional Risk Factors ◽  
Regulatory Functions

Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as systemic inflammation mediators, including cytokines, chemokines, proteases, autoantibodies, adhesion receptors, and others, have been implicated in the development of these vascular pathologies. Yet, the characteristics of vasculopathies may significantly differ depending on the underlying disease. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been further detected. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Epigenetic regulatory mechanisms comprise DNA methylation, histone modifications, and microRNA activity, all of which act upon gene and protein expression levels. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, not only showing differences between AID patients and healthy controls, but also showing how one disease differs from another and even how the expression of key proteins involved in the development of each disease is regulated.

CD24High / FLJ/P1Low Expression Correlates with Bad Prognosis and Shorter Survival in Adult ALL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1451-1451
Author(s):  
Lionel J. Coignet ◽  
Thimothy Johnson ◽  
Alain Nganga ◽  
Qing Zhang ◽  
Corinna Meyer ◽  
...  
Keyword(s):  
Cell Line ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Active Form ◽  
Mitochondrial Protein ◽  
Chromosomal Translocation ◽  
Genetic Alterations ◽  
Leukemia Cells ◽  
Chromosome Band ◽  
Hematopoietic Stem

Abstract Leukemia is a neoplastic proliferation of cells of hematopoietic origin that arises following somatic mutation in a single hematopoietic stem cell, the progeny of which forms a clone of leukemia cells. Genetic alterations leading to leukemia transformation of a cell are often associated with major alterations of chromosomes that can be detected by studying cells of the leukemic clone in mitosis. One of these alterations is a chromosomal translocation that is often used to identify genes potentially involved in other type of rearrangements such as deletions. Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (ALL), in differentiated and undifferentiated acute myeloid leukemia (AML) and in chronic myeloid leukemia at progression to blast crisis (CML-BC). Recently, we have shown the presence of a myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia (Genes Chromosome Cancer 25:222–229,1999). In addition, a new cell line has been established from one of the lymphoid cases, MUTZ5, that carries a single t(12;13) translocation (Leukemia 15:1471–1474, 2001). The molecular characterization of this translocation led to the identification of a new gene, FLJ13639, that is disrupted and lost in the MUTZ5 cell line. This gene shares homologies with the large family of short-chain dehydrogenase reductase (SDR). Furthermore, three transcripts and proteins were found to be differentially expressed for this gene, where P1 is potentially the active form of dehydrogenase, while P2 and P3 are lacking the co-activator site. We report here that one of the consequences of the loss of FLJ13639 is the over-expression of CD24 that appears to provide leukemia cells with a proliferation and invasiveness advantage, as well as a certain degree of chemoresistance. FLJ13639 is a new mitochondrial protein that seems to be important for the respiration and apoptosis processes. In addition, semi-quantitative RT-PCR for CD24 and FLJ13639/P1 was performed in a series of cell lines as well as 29 adult ALL samples at diagnosis. Fifty percent of the samples showed a CD24High / FLJ/P1Low profile whereas the remaining samples showed either a balanced expression or a CD24Low / FLJ/P1High profile. These preliminary data on patient samples indicated a correlation between survival and CD24High / FLJ/P1Low expression profile (p=0.04). The current median time survival for the CD24High / FLJ/P1Low group is 9 months whereas the CD24Low / FLJ/P1High group is 28 months. Therefore, this appears to be a new potential prognostic marker for adult ALL. Figure Figure

scholarly journals Absence of an Orphan Mitochondrial Protein, C19orf12, Causes a Distinct Clinical Subtype of Neurodegeneration with Brain Iron Accumulation

2011 ◽  
Vol 89 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Monika B. Hartig ◽  
Arcangela Iuso ◽  
Tobias Haack ◽  
Tomasz Kmiec ◽  
Elzbieta Jurkiewicz ◽  
...  
Keyword(s):  
Mitochondrial Protein ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Clinical Subtype

Blueberry muffin baby syndrome – praca poglądowa

2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Bartosz Chyżyński ◽  
Michał Matysiak
Keyword(s):  
Skin Lesions ◽  
Underlying Disease ◽  
Diagnostic Process ◽  
Skin Symptom ◽  
Congenital Rubella ◽  
Common Causes ◽  
Therapeutic Procedures ◽  
Rubella Virus Infection ◽  
Disease Entities ◽  
First Time

Blueberry muffin baby syndrome is a nonspecific skin symptom characterized by the presence of blue-red, purple, small skin lesions with a coherent consistency, size from 1-5 mm, which have historically been described for the first time in newborns with congenital rubella virus infection. Originally, these changes were associated with the presence of persistent fetal dermal erythropoiesis during the fetal period. We now know that the described changes may be related not only to infectious disorders, but also to other disease entities ranging from hematological, vascular and metabolic disorders to neoplastic diseases including neonatal period. The image of skin lesions depending on the underlying disease may be significantly different. To our knowledge, at present there is no generally accepted algorithm for diagnostic and therapeutic procedures in patients with blueberry muffin skin changes. Knowledge about the most common causes underlying the symptom of bluberry muffin baby syndrome is the key to conducting an efficient diagnostic process, establishing a diagnosis and implementing a quick and effective treatment appropriate for the underlying blueberry muffin disease.

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