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Biomedical subjects

Richard Kellermayer

Publications and source records attributed to Richard Kellermayer.

At least 19 recordsLinked to original sources
PubMed2026

Brief Review: Rethinking Colonic Redundancy in Gastroenterology.

BACKGROUND: Dolichocolon (DC), or colonic redundancy, is an elongated and tortuous colon described as early as 1820, yet it remains underrecognized in clinical gastroenterology. Advances in imaging and motility assessment offer new insights into its prevalence, mechanisms, and clinical implications. AIMS: To summarize current evidence on the anatomy, epidemiology, and potential clinical significance of DC and to explore possible pathophysiological mechanisms linking this variant to gastrointestinal disorders. METHODS: A targeted literature review of studies published between 1900 and 2024 was conducted using PubMed and Scopus with search terms including dolichocolon, colonic redundancy, and redundant colon. Publications addressing anatomy, motility, symptom associations, and disease relevance were included. RESULTS: Though epidemiological data are limited, it has been estimated that DC affects 10-20% of the population and is associated with constipation, volvulus, and, possibly, inflammatory bowel disease. Proposed mechanisms include segmental stasis and ischemia in redundant loops, altered neuromuscular signaling, and increased mucosal surface area promoting immune-microbiota interactions. Despite its potential importance, DC is rarely noted in modern radiology reports, contributing to under-recognition in clinical practice. CONCLUSIONS: Colonic redundancy represents a common anatomic variant with potentially overlooked clinical implications. Standardized radiologic characterization and prospective studies are needed to clarify its role in gastrointestinal disorders and to guide future diagnostic and therapeutic approaches.

Humans↗
PubMed2026

Dolichocolon May Differentially Associate with Ulcerative Colitis Phenotype in Children.

BACKGROUND: Dolichocolon (DC) is an underrecognized anatomic variant associated with constipation; its association with ulcerative colitis (UC) is unknown. METHODS: We retrospectively reviewed abdominal MRI and CT scans in children with UC, Crohn's disease (CD), and non-inflammatory bowel disease (non-IBD) controls, classifying DC subtypes. RESULTS: A total of 111 cases (66 with UC) were examined. DC was similarly common (p = 0.4436) in patients with constipated (69%) or non-constipated (NC-UC: 57%) UC. In non-constipated (NC) patients, DC prevalence was higher in children with UC than those with CD or controls. Type 1 DC predominated in NC children with proctitis/left-sided UC (E1/E2), while Type 2 DC was enriched in children with extensive/pancolitis (E3/E4). DISCUSSION: DC may be associated with different phenotypes of UC and may influence disease distribution independent of constipation. However, given the cross-sectional design of this study, these associations should be interpreted cautiously and require confirmation in longitudinal studies.

Humans↗
PubMed2024

Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune-mediated liver injury.

Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intrahepatic and extrahepatic bile ducts of unclear etiology. PSC is commonly (in 60%-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation. Here, we review recent epidemiologic observations and highlight that PSC-IBD and PSC-AIH overlap appear to represent aspects of a common PSC clinico-pathological pathway and manifest in an age-of-presentation-dependent manner. Particularly from the pediatric experience, we hypothesize that all cases of PSC likely originate from a complex "Early PSC"-"IBD"-"AIH" overlap in which PSC defines the uniquely and variably associated "AIH" and "IBD" components along an individualized lifetime continuum. We speculate that a distinctly unique, "diverticular autoimmunity" against the embryonic cecal- and hepatic diverticulum-derived tissues may be the origin of this combined syndrome, where "AIH" and "IBD" variably commence then variably fade while PSC progresses with age. Our hypothesis provides an explanation for the age-dependent variation in the presentation and progression of PSC. This is critical for the optimal targeting of studies into PSC etiopathogenesis and emphasizes the concept of a "developmental window of opportunity for therapeutic mitigation" in what is currently recognized as an irreversible disease process. The discovery of such a window would be critically important for the targeting of interventions, both the administration of current therapies and therapeutic trial planning.

Humans↗
PubMed2006

Lithium suppresses epidermal SERCA2 and PMR1 levels in the rat.

Autosomal dominant mutations in the genes encoding the calcium ATPases SERCA2 and PMRI/SPCA1 cause the genodermatoses Darier disease (DD) and Hailey-Hailey disease (HHD), respectively. Recent observations indicated that the level of the pathogenic proteins greatly decreases in the affected areas of the epidermis in these disorders. Here we addressed how lithium, a recognized exacerbating factor in Darier disease, affects the epidermal expression of SERCA2 and PMR1/SPCA1 in the rat as a model. Standard histologic and immunohistochemical methods were utilized in 3 lithium-treated and 3 control animals. A significant suppression of epidermal SERCA2 and PMR1 levels were observed as a result of lithium therapy in addition to marked qualitative and quantitative changes in the stratum corneum and the granular layer of the epidermis in the treated animals. Our findings suggest that exacerbating factors in calcium ATPase disorders of the skin suppress epidermal SERCA2 and PMR1 levels, further decreasing the already haploinsufficient protein expression to a potentially critical level in Darier disease and Hailey-Hailey disease, respectively. Lithium therapy should specifically be avoided not only in Darier disease, but Hailey-Hailey disease as well.

Animals↗
PubMed2006

Autosomal-dominant calcium ATPase disorders.

Darier disease (DD) and Hailey-Hailey disease (HHD) are the only known autosomal-dominant Ca2+ ATPase disorders. Epidermal symptoms selectively occur in the affected individuals, the precise reason for which is still not fully understood. Here, we review the clinical, epidermal, and molecular features of the two genodermatoses. It is concluded that epidermal Ca2+ regulation disturbances and epigenetic factors may play an even more prominent role in the pathogenesis of DD and HHD than earlier appreciated.

Calcium-Transporting ATPases↗
PubMed2006

Translational readthrough induction of pathogenic nonsense mutations.

The treatment of genetic disorders is one of the biggest challenges lying ahead of modern medicine. While major advancements have been made in gene therapy, it is still far from achieving clinical success. However, other potential methods for treating single gene related diseases have also emerged recently. One such approach is the suppression of pathogenic nonsense mutations through inducing translational readthrough of the in-frame premature stop mutation. Aminoglycosides were the first drugs that gave promising results in this respect. This report provides a brief overview on the past, present and potential future of this pharmacogenetic approach.

Aminoglycosides↗
PubMed2006

A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders. Irrespective of the genetic defect, patients with SCID may be engrafted with transplacentally derived maternal T-lymphocytes that in a subset of cases may be responsive to phytohemagglutinin. Here, we present, from a genetic perspective, an SCID patient who not only harbored a novel mutation in the gene encoding the common gamma chain (gamma c) of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes that produced a karyotype that was initially perplexing.

Base Sequence↗
PubMed2006

The versatile RECQL4.

The human DNA helicase RECQL4 interacts in an array of intracellular regulatory pathways from the initiation of DNA replication, through maintaining genomic stability, to the N-end rule pathway. Interestingly, mutations in RECQL4 have recently been revealed not only in Rothmund-Thomson-, but RAPADILINO-, and cases of Baller-Gerold syndrome also. Although these disorders represent distinct genetic entities, clinical observations have delineated highly variable expressivity and significant overlaps in the associated phenotypic manifestations. Consequently, it is especially difficult to draw precise genotype-phenotype correlations in RECQL4 related syndromes. This is likely due to the complex and multiple cellular networks RECQL4 is associated with.

Abnormalities, Multiple↗
PubMed2005

Electrically induced gel-to-gel phase-transition in neurons.

At the end of transcardial perfusions with ice-cold physiological saline for 30 min or with isoosmotic potassium chloride for 5 min, but immediately before perfusion fixation, condenser-discharge electric shocks were administered to rats through surface electrodes pressed onto the temporal muscles of the scalped skull. As a result, striking ultrastructural compaction came about in numerous neurons thinly scattered in certain brain areas. Its features displayed a high degree of similarity to those previously observed following the in vivo administration of the same kind of electric shocks. This surprising independence from the actual state of metabolism questions whether the ultrastructural compaction, induced either in vivo or post mortem, is the result of any cascade of enzyme-mediated processes. On the other hand, a physical mechanism, phase transition propagated by non-covalent free energy stored in a cytoplasmic gel structure, which was proposed recently to explain a mechanically induced similar ultrastructural compaction, appears to apply also to the present case.

Animals↗
PubMed2005

Calcium and magnesium competitively influence the growth of a PMR1 deficient Saccharomyces cerevisiae strain.

PMR1, the Ca2+/Mn2+ ATPase of the secretory pathway in Saccharomyces cerevisiae was the first member of the secretory pathway Ca2+ ATPases (SPCA) to be characterized. In the past few years, pmr1Delta yeast have received more attention due to the recognition that the human homologue of this protein, hSPCA1 is defective in chronic benign pemphigus or Hailey-Hailey disease (HHD). Recent publications have described pmr1Delta S. cerevisiae as a useful model organism for studying the molecular pathology of HHD. Some observations indicated that the high Ca2+ sensitive phenotype of PMR1 defective yeast strains may be the most relevant in this respect. Here we show that the total cellular calcium response of a pmr1Delta S. cerevisiae upon extracellular Ca2+ challenge is decreased compared to the wild type strain similarly as observed in keratinocytes. Additionally, the novel magnesium sensitivity of PMR1 defective yeast is revealed, which appears to be a result of competition for uptake between Ca2+ and Mg2+ at the plasma membrane level. Our findings indicate that extracellular Ca2+ and Mg2+ competitively influence the intracellular Ca2+ homeostasis of S. cerevisiae. These observations may further our understanding of HHD.

Calcium↗
PubMed2005

Hailey-Hailey disease as an orthodisease of PMR1 deficiency in Saccharomyces cerevisiae.

The term orthodisease has recently been introduced to define human disorders in which the pathogenic gene has orthologs in model organism genomes. Here, we describe Hailey-Hailey disease (HHD), a blistering skin disorder caused by haploinsufficiency of ATP2C1 as an orthodisease from a Saccharomyces cerevisiae perspective. ATP2C1 encodes the human secretory pathway Ca(2+)/Mn(2+) ATPase hSPCA1 and is orthologous to the PMR1 gene in S. cerevisiae. hSPCA1 fully complements PMR1 deficiency in yeast and pmr1DeltaS. cerevisiae has proved to be a valuable tool to screen ATP2C1 mutations and address potential pathogenic/pharmacologic mechanisms in HHD. Consequently, this human skin disorder is an ideal example of an orthodisease.

Calcium-Transporting ATPases↗