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At least 1,153 records · Page 64Linked to original sources
PubMed1997

[Current lymphoma classification: a step forward for pathologists and clinicians].

Non-Hodgkin lymphomas encompass a heterogeneous group of lymphoid malignancies from the clinical as well as from the pathological point of view. Consequently, one condition of optimal communication among pathologists, clinicians and scientific researchers is an adequate classification system. A new classification of lymphomas was proposed in September 1994, the Revised European-American Lymphoma Classification (REAL classification). The REAL classification is aiming at integration of pathological and clinical data, making it possible to distinguish clinical-pathological entities each of which has its characteristic pathological spectrum, clinical evolution and clinical presentation. The REAL classification is based not only on morphological and immunohistochemical but also on molecular and cytogenetic data. Such a system may make it possible to develop specific therapies for specific pathological entities. The REAL classification constitutes an important step forward in haemato-oncology.

Hodgkin Disease↗
PubMed1986

Selection for increased mutation rates with fertility differences between matings.

Previous studies of mutation modification have considered models in which selection is a result of viability differences that are sex symmetric. The results of a numerical study of a model in which selection is a result of fertility differences between mated pairs demonstrate that the type of selection to which a population is subject can have a significant impact on the evolution of various parameters of the genetic system. When the fertility of matings between individuals with different genotypes exceeds the fertility of at least some of the matings between individuals with the same genotype, selection may favor increased rates of mutation, in contrast to the results from all existing constant viability models with random mating and infinite population size. Increased mutation rates are most frequently favored when forward and back mutation occur at approximately equal rates and when the modifying locus is loosely linked to the selected locus. We present one example in which selection favors increased rates of mutation even though the selection scheme is reducible to one of differential viability between the sexes.

Alleles↗
PubMed2004

Beyond the double helix: writing and reading the histone code.

Chromatin is the physiological carrier of not only genetic information, encoded in the DNA, but also of epigenetic information including DNA methylation and histone modifications. As such histone modifications are involved in many aspects of nuclear processes including gene regulation and chromosome segregation. Recently, a 'histone code' hypothesis was put forward to explain how patterns of histone modification may function in downstream processes. In support of the 'histone code' hypothesis, we found in vivo and in vitro evidence that effector proteins, HP1 (heterochromatin protein 1) and Pc (Polycomb) can discriminate and 'read' histone methylation marks on K9 and K27, respectively. Moreover, we propose a 'binary switch' model and suggest that binding and release of effector proteins to their cognate sites can be regulated by modifications on adjacent or nearby residues. Thus, combinations of adjacent histone modifications would function differently from singular modification, and static modifications (e.g. Lys methylation) may well be regulated by dynamic modifications (e.g. phosphorylation). Finally, we describe a novel histone phosphorylation event linking the function of Mst1 kinase and H2B Ser14 phosphorylation with apoptotic chromatin condensation in vertebrates. As this modification is not found during mitotic chromosome condensation, these findings suggest the intriguing possibility that a unique 'death' mark exists for chromatin condensation during apoptosis.

Acetylation↗
PubMed2003

[Genetic causes of retinal degeneration].

Premature death of rod and cone photoreceptor cells in the human retina leads to severe visual handicaps in affected patients. The two most important groups of retinal dystrophies, macular degeneration and retinitis pigmentosa, differ in primary symptoms and disease progression. Macular degeneration starts in the central retina and progresses towards the periphery. In RP, photoreceptor cell death starts in the periphery and then proceeds to the central part of the retina. Molecular studies have revealed important new findings during the last decade. There are two important results to be emphasized: 1. The very same clinical symptoms can result from mutations in different genes. RP is a prominent example for this phenomenon. 2. Mutations in the same gene can result in different phenotypes. The correlation between genotype and phenotype is not essentially straight forward. This may indicate that other factors can influence the phenotypic consequences of mutations. Different X-linked retinal dystrophies represent excellent examples for these findings.

Adult↗
PubMed2001

[Cell determination and differentiation: a concept of gene clusters].

This paper formulates a conception of cluster organization of the genetic material, responsible for cell determination and differentiation in multicellular organisms. According to this conception, gene controlling each particular stage of these processes are functionally integrated via genes-activators into gene groups (clusters) of different levels of hierarchy. Besides, some hypotheses of molecular mechanisms providing the action of these gene groups have been put forward. Attempts were made to elucidate some phenomena of cell differentiation, specifically a drop or a complete loss of dividing ability in highly specialized cells, in addition to a property of the cell to remember the history of its own development inside the organism, and to inherit the ancestor's direction of differentiation. Attention was paid to a mechanism (originating from this conception) of the emergency of malignant tumors, which means that cells giving rise to tumors are known to evade primarily their involvement in the process of further specialization. Besides, mechanisms of a molecular supply of positional information are examined. Phylogenetic aspects concerning the standing of the fragment of genetic apparatus controlling cell specialization, and the development of its inner hierarchy that involves subordination of some clusters to other ones.

Animals↗
PubMed2006

Genetics of chronic obstructive pulmonary disease, beyond a1-antitrypsin deficiency.

It is known that only 10-20% of smokers develop COPD, implying that apart from environmental features, additional factors such as genetic variability contribute to smoke susceptibility. This proposal is in compatibility with the "Dutch Hypothesis", formulated in the early 60's. Alpha-1-antitrypsin gene was implicated in the pathogenesis of COPD, especially the homozygous state of z allele. Since then many other genes have stepped forward as possible contributors to COPD development. In the present review we attempt to summarize the majority of these, including the genes of matrix metalloproteinases and their inhibitors, elastin, serpine2, tumor necrosis factor - a, transforming growth factor beta, a variety of interleukins and their receptors and antagonists, high affinity IgE receptor , human calcium-activated chloride channel 1, heme oxygenase, vascular endothelial growth factor, microsomal epoxide hydrolase, glutathione S-transferase, cytochrome P45O, superoxide dismutase, vitamin D binding protein, beta2-adrenergic receptor, Toll like receptor, human B defensins, mucins, cystic fibrosis transmembrane regulator, surfactant protein and Nuclear Factor E2 Related Factor 2.

Alleles↗
PubMed2006

Disrupted in schizophrenia 1: building brains and memories.

Schizophrenia and bipolar affective disorder are common, debilitating, and poorly understood and treated disorders. Both conditions are highly heritable. Recent genetic studies have suggested that the gene disrupted in schizophrenia 1 (DISC1) is an important risk factor. DISC1 seems to have a key role in building the brain and memories by interacting with other proteins, including nuclear distribution E-like protein and phosphodiesterase 4B. Here, we review the current knowledge, highlight some key unanswered questions and propose ways forward towards a better understanding of normal and abnormal brain development and function. In the long term, this might lead to the discovery of drugs that are more efficacious and safer than currently available ones.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer's disease.

It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.

Alcoholism↗
PubMed2004

Janus kinase-3 (JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation.

Current immunosuppressive therapy in clinical organ transplantation is based on drugs that suppress various functions of immunocompetent cells but still affect cells and organ compartments other than the immune system. Hence, these drugs have considerable side effects which lead to increased morbidity and reduced life-quality of transplant recipients. A major step forward in the rationale design of clinical immunosuppression resides in the elucidation of molecular targets that play a critical role specifically within the immune system. Recently, Janus kinase 3 (JAK3) has been identified as such a molecule. Genetic absence or ablation of this tyrosine kinase is associated with defective T-cell immunity that results in severe combined immunodeficiency (SCID) without apparent changes in other organ systems. Furthermore, pharmacological inhibition has significantly prolonged allograft survival in several experimental models of organ transplantation. The present review provides an overview of the emerging role of JAK3 in the immune system and the development of JAK3-inhibiting drugs. The potential clinical application of JAK3 inhibitors in organ transplantations is discussed in the light of a recent series of successful kidney transplantations in non-human primates immunosuppressed solely with a novel JAK3 inhibitor.

Animals↗
PubMed2026

Omics in optic neuropathies: From molecular landscapes to personalized therapeutics.

Optic neuropathies comprise a heterogeneous group of disorders involving transient or permanent injury to retinal ganglion cells (RGCs) and their axons. Clinically, these neurodegenerative conditions manifest as dyschromatopsia, decreased visual acuity, and visual field defects, and in severe cases may ultimately lead to blindness and disability. The marked heterogeneity across disease subtypes, incompletely understood etiologies, and complex pathogenic mechanisms pose substantial challenges to precise diagnosis and effective treatment. Recent advances in omics technologies - including genomics, transcriptomics, proteomics, metabolomics, lipidomics, single-cell and spatial sequencing, and integrative multi-omics approaches - have ushered optic nerve degenerative disease research into an era of high-resolution comprehensive investigation. In this review, we summarize representative applications of omics approaches to elucidate genetic alterations, signaling dysregulation, metabolic reprogramming, and immune responses in optic neuropathies. We further discuss the emerging potential of multi-omics in identifying early diagnostic biomarkers and informing individualized therapeutic strategies. Finally, we provide a forward-looking perspective on the future trajectory of omics technologies and their prospects in both fundamental research and clinical translation, with the overarching aim of accelerating the bench-to-bedside transition in this critical eye disease field.

biomarkers↗
PubMed1989

Anticipation in myotonic dystrophy: fact or fiction?

In 1918 Fleischer reported that after transmission from one generation to the next, myotonic dystrophy has an earlier onset and is more severe. The hypothesis put forward by Penrose in 1948 that 'anticipation' is caused by bias of index case selection was based on theoretical arguments only and has not been supported by clinical observations. This hypothesis was tested in a clinical and genetic study of 14 families with myotonic dystrophy. Excluding index patients, an earlier onset in the child was found in 98% of 61 parent-child pairs. A greater mean difference in age of onset was found with transmission via the father than via the mother. The comparison of the severity of the disease between parents and children was difficult because of the variation in symptoms but, in general, the disease was more severe in the child than in the parent. The penetrance of the abnormal gene was nearly complete in the 14 families combined, leaving little room for the observation of 'complementary' parent-child pairs in the future. Also in retrospect no complementary parent-child pairs were found in the first generations. Fertility was severely reduced only in the very early onset patient group and this selective infertility cannot be responsible for the total amount of anticipation observed. It is therefore concluded that anticipation may be inherent in the transmission of myotonic dystrophy. This has important consequences for genetic counselling.

Adult↗
PubMed2005

[Adjunctive reflections on history of hematopoietic stem cell study--editorial].

The article reviews concisely around the history of hematopoietic stem cell research, basic and clinical, since its very beginning after the nuclear explosions at the end of the Second World War, that explains why the stem cell study in the world began with the hematopoietic stem cells and the existence of non-hematopoietic stem cell in vivo had been left out of account for many decades till 21st century. During 50-60s of the last century, it was known from the animal experiments that there must be hematopoietic stem cells existing in vivo and believed that the effective bone marrow transplant is actually the stem cell transplantation. It is reviewed how the basic studies of stem cell interacted with the clinical stem cell transplantation and how great the contribution was given to strongly push forward the development of contemporary stem cell biology and modern hematology from the basic studies especially in the immunological and molecular biological fields, for instance, the applications of HLA technology and monoclonal antibody produced, flow cytometry, and genetic recombinant cytokines, the novel technique for gene cloning, genomics, proteomics, and iRNA as well as bioinformatics. It has lead to the pluralistic cell therapy as a novel trend in stem cell transplantation as to combine immunotherapy and mesenchymal stem cells with the conventional stem cell transplants. This paper looks back in the past several decades, however, on every achievement of stem cell study that were usually accompanied with some idealistic one-sidedness or even errors in design and conclusion of some experiments. Usually it took a period of 2 or even 4 decades to clarify some basic idea, that seemed normal in the science development, for examples, the dividing line between the hematopoietic stem cell and progenitor cells, possibility to expand or clone the real stem cell ex vivo, and whether the majority of leukemias are originated from stem cell level, etc. Towards the end of 20th century, the greatest discovery was the existence of adult stem cells in adult tissues, which are no doubt the remnants from the embryonic development including all stages of embryonic stem cells, very earlier and later, hematopoietic and nonhematopoietic, and could be induced to differentiate into all kinds of tissue cells by proper ways in vitro. No evidence has really provided for the hypothesis of so called trans-differentiation or de-differentiation, which brought about strong calls in questions in the past 5 years. The problems in developing the clinical gene therapy by using hematopoietic stem cell as carrier of interested gene still remained to be solved so far. Because of the relatively weak base of related basic studies, the clinical application of gene therapy resulted in the failure of clinical practice with lots of lessons towards the end of last century. The whole history of stem cell study in the world was an endless process of continuous redress for theoretical ideas in stem cell biology that had never been consummate.

Hematopoietic Stem Cells↗
PubMed1994

[Genetic predisposition to latent influenza A virus in children with blood type B(III) as a possible cause of new epidemiologic strains in the countries of South-Eastern Asia].

Regular clinical and epidemiological surveys of two groups of healthy 14-16-year-old boys were carried out for 3 years from September 1989 to May 1992 to investigate the latent circulation of influenza A viruses in the human population. Once or twice a quarter clinical materials were laboratorily studied to detect virus antigens, virus-specific NA-sequences and to determine changes in humoral immunity. The latent circulation of influenza A viruses might be identified in 10-20% of cases long before (2-4 months) the onset of epidemic development. The incidence of epidemic isolations was found to reach 33-36%, gradually decreasing from 29 to 9 or 3.5% in the postepidemic period. The long-term persistence (for 5 months) of virus antigens was reported among healthy children who had chiefly blood group B(III). The new hypothesis that the genetic predisposition of children with blood group B(III) to latent persistence of influenza A viruses may be a possible cause of the emergence of new epidemic strains in the South-East Asian countries has been forwarded.

ABO Blood-Group System↗
PubMedDate not supplied

[Primary severe neonatal hyperparathyroidism. Significance of genetic study and emergency parathyroidectomy].

Primary hyperparathyroidism in the newborn is uncommon. The clinical features as well as histological lesions of the parathyroid glands are quite different from those in the adult. The degree of hypercalcemia and the high frequency of pulmonary complications may threaten the life of the infant. Management is straight forward: early surgical removal and supplementation with calcium and vitamins should be quickly followed by an autograft. In the severe case herein reported, the diagnosis, suggested by family history, was confirmed by a rapid increase in calcemia as well as by very characteristic skeletal lesions.

Consanguinity↗
PubMedDate not supplied

The effects of estrogen on short-term memory in genetic men.

BACKGROUND: The subject of estrogen in regard to short-term memory is controversial. There is support in the medical literature for estrogen improving short-term memory in women, but there are few data on this subject pertaining to genetic men. OBJECTIVE: To examine the effects of supplemental estrogen on short-term memory in genetic men. DESIGN: A matched control study. SETTING: Private interview rooms. PARTICIPANTS: The variable group consisted of 31 transsexual men taking estrogen to change their gender. The control group comprised 31 age- and education- matched men not taking estrogen. In addition, a group of four subjects not initially taking estrogen was studied immediately before and for a short time after initiating estrogen therapy. MEASUREMENTS: Short-term memory was evaluated by four accepted short-term memory tests dealing with digits, words, and sentences. RESULTS: Three of the four short-term memory tests showed statistical significance favoring the estrogen-treated subjects. The Wechsler Adult Intelligence Scale-Revised Digit Span for Digits Forwards (Test 1) showed a trend toward improvement. The Wechsler Adult Intelligence Scale-Revised Digit Span for Digits Backwards (Test 2), the Woodcock-Johnson Tests of Cognitive Ability Memory for Words (Test 3),Sentences (Test 4) all showed statistical significance. CONCLUSIONS: Results support the hypothesis that estrogen enhances short-term memory in genetic men. This study, in conjunction with others, indicates the possible usefulness of estrogen therapy in the treatment of Alzheimer's disease.

Journal Article↗
PubMed2001

Genetic aspects of psoriasis.

Epidemiological studies indicate that genes play an important role in the pathogenesis of psoriasis. Multiple genes are likely to be involved, interacting not only with each other but also with the environment to cause disease expression. Molecular genetic studies indicate that there are multiple susceptibility loci present throughout the human genome. It is clear that a gene or genes of major impact on psoriasis is present on chromosome 6 within the major histocompatibility complex (MHC). Linkage disequilibrium studies indicate this gene to reside within a 300 kb interval centred around the centromeric end of class I MHC. Known candidate genes in this region are HLA-C, corneodesmosin and HCR, although novel genes, as yet unknown, may also exist. There is accumulating evidence that HLA-C is not itself the causative gene but rather a marker for it. Identification of the genes involved in psoriasis susceptibility will represent a step forward in our understanding of the disease and our future ability to help patients with psoriasis.

Adult↗