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Article ; Online: The Inability of Podocytes to Proliferate: Cause, Consequences, and Origin.

Kriz, Wilhelm

Anatomical record (Hoboken, N.J. : 2007)

2019 Volume 303, Issue 10, Page(s) 2588–2596

Abstract: This study presents a theoretical analysis of the problems related to the inability of podocytes to proliferate. The basis of these problems is the very high rate of glomerular filtration. Podocytes do not in general die by apoptosis or necrosis but are ... ...

Abstract	This study presents a theoretical analysis of the problems related to the inability of podocytes to proliferate. The basis of these problems is the very high rate of glomerular filtration. Podocytes do not in general die by apoptosis or necrosis but are lost by detachment from the glomerular basement membrane (GBM) as viable cells. Podocytes situated on the outside of the filtration barrier and attached to the GBM only by their foot processes are permanently exposed to the flow dynamic forces of the high filtration rate tending to detach them from the GBM. The major challenge seems to consist of the high shear stresses on the foot processes within the filtration slits due to filtrate flow. Healthy podocytes are able to resist this challenge, injured podocytes are not, and may undergo foot process detachment, leading to a gap in the podocyte cover of the GBM. This represents a mortal event. Like a dam break, such a leak cannot be repaired. The ongoing exposure to filtrate flow prevents any attempt to close the gap, thus preventing any regeneration including cell proliferation. An improvement of this precarious situation consists of healing by scarring that may involve only one lobule of the glomerulus, permitting the remaining lobules to maintain filtration. An answer to the question of which waste product requires such a high filtration rate for its excretion may be in the huge quantity of circulating peptides, a problem that dates far back in evolution.
MeSH term(s)	Animals ; Cell Proliferation/physiology ; Glomerular Basement Membrane/cytology ; Humans ; Podocytes/cytology ; Stress, Mechanical
Language	English
Publishing date	2019-10-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2269667-2
ISSN	1932-8494 ; 1932-8486
ISSN (online)	1932-8494
ISSN	1932-8486
DOI	10.1002/ar.24291
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Article ; Online: Maintenance and Breakdown of Glomerular Tuft Architecture.

Kriz, Wilhelm

Journal of the American Society of Nephrology : JASN

2018 Volume 29, Issue 4, Page(s) 1075–1077

MeSH term(s)	Extracellular Matrix Proteins ; Kidney Glomerulus ; Mesangial Cells
Chemical Substances	Extracellular Matrix Proteins ; nephronectin
Language	English
Publishing date	2018-03-13
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2018020200
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Zs.A 3344: Show issues

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Article ; Online: The complex pathology of diabetic nephropathy in humans.

Kriz, Wilhelm / Löwen, Jana / Gröne, Hermann-Josef

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2023 Volume 38, Issue 10, Page(s) 2109–2119

Abstract: This review summarizes the pathomorphological sequences of nephron loss in human diabetic nephropathy (DN). The relevant changes may be derived from two major derangements. First, a failure in the turnover of the glomerular basement membrane (GBM) based ... ...

Abstract	This review summarizes the pathomorphological sequences of nephron loss in human diabetic nephropathy (DN). The relevant changes may be derived from two major derangements. First, a failure in the turnover of the glomerular basement membrane (GBM) based on an increased production of GBM components by podocytes and endothelial cells leading to the thickening of the GBM and accumulation of worn-out GBM in the mesangium. This failure may account for the direct pathway to glomerular compaction and sclerosis based on the continuous deposition of undegraded GBM material in the mesangium. Second, an increased leakiness together with an increased propensity of glomerular capillaries to proliferate leads to widespread plasma exudations. Detrimental are those that produce giant insudative spaces within Bowman's capsule, spreading around the entire glomerular circumference and along the glomerulo-tubular junction onto the tubule resulting in tubular obstruction and retroactively to glomerulosclerosis. Tubular atrophy and interstitial fibrosis develop secondarily by transfer of the glomerular damage onto the tubule. Interstitial fibrosis is locally initiated and apparently stimulated by degenerating tubular epithelia. This leads to a focal distribution of interstitial fibrosis and tubular atrophy accompanied by a varying interstitial mononuclear cell infiltration. Spreading of fibrotic areas between intact nephrons, much less to the glomerulus, has not been encountered.
MeSH term(s)	Humans ; Diabetic Nephropathies/pathology ; Endothelial Cells/metabolism ; Glomerular Basement Membrane/metabolism ; Fibrosis ; Atrophy/pathology ; Diabetes Mellitus/pathology
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfad052
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Zs.A 2198: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mesangial Injury and Capillary Ballooning Precede Podocyte Damage in Nephrosclerosis.

Kriz, Wilhelm / Wiech, Thorsten / Gröne, Hermann-Josef

The American journal of pathology

2022 Volume 192, Issue 12, Page(s) 1670–1682

Abstract: The development of focal and segmental glomerulosclerosis (FSGS) as a consequence of glomerular hypertension resulting from arterial hypertension is widely considered a podocyte disease. However, the primary damage is encountered in the mesangium. In ... ...

Abstract	The development of focal and segmental glomerulosclerosis (FSGS) as a consequence of glomerular hypertension resulting from arterial hypertension is widely considered a podocyte disease. However, the primary damage is encountered in the mesangium. In acute settings, mesangial cells disconnect from their insertions to the glomerular basement membrane, causing a ballooning of capillaries and severe changes of the folding pattern of the glomerular basement membrane, of the arrangement of the capillaries, and thereby of the architecture of the tuft. The displacement of capillaries led to contact of podocytes and parietal epithelial cells, initiating the formation of tuft adhesions to Bowman's capsule, the committed lesion to progress to FSGS. In addition, the displacement of capillaries also caused an abnormal stretching of podocytes, resulting in podocyte damage. Thus, the podocyte damage that starts the sequence to FSGS is predicted to develop secondary to the mesangial damage. This sequence was found in two hypertensive rat models of FSGS and in human hypertensive nephrosclerosis.
MeSH term(s)	Rats ; Humans ; Animals ; Podocytes/pathology ; Glomerulosclerosis, Focal Segmental/pathology ; Nephrosclerosis/complications ; Capillaries/pathology ; Glomerular Basement Membrane/pathology ; Hypertension, Renal/complications
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2022.08.007
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Article: Padaczka z obecnościa wyładowań iglicowych w okolicy centrośrodkowej (pole Rolando). Szczególna postać drgawek w dzieciństwie.

Kriz, M / Gazdik, M

Neurologia i neurochirurgia polska

1978 Volume 12, Issue 4, Page(s) 413–419

Abstract: The study presents the results of a long term investigation of 60 epileptic children with Rolandic (centrotemporal) spikes in EEG. The results could be summarized as follows: the Rolandic epilepsy is relatively frequent entity (13.4% of the total number ... ...

Title translation	Epilepsy with centrotemporal (Rolandic) spikes. A peculiar seizure disorder of childhood.
Abstract	The study presents the results of a long term investigation of 60 epileptic children with Rolandic (centrotemporal) spikes in EEG. The results could be summarized as follows: the Rolandic epilepsy is relatively frequent entity (13.4% of the total number of epileptic children). The age span was from 3--13 years, with a peak of age incidence between the 7th and 8th year of life. More than half of children had nocturnal fits only. From the clinical point of view 60% of children had generalized crises, and the remaining 40% had partial attacks corresponding to the functional organization of the Rolandic cortical area. The evolution of the Rolandic epilepsy in childhood is favourable. More than 50% didn't have more attacks after the introduction of antiepileptic therapy, and 3/4 of them could be classified as practically cured after an long-term follow-up (criterion: an attack-free period of at least 5 years. Finally, in more than 80% of cases after three years of follow-up the spikes have disappeared from the EEG tracings which were completely normal.
MeSH term(s)	Adolescent ; Age Factors ; Child ; Child, Preschool ; Diagnosis, Differential ; Electroencephalography ; Epilepsies, Partial/diagnosis ; Epilepsies, Partial/epidemiology ; Humans ; Terminology as Topic
Language	Polish
Publishing date	1978-07
Publishing country	Poland
Document type	English Abstract ; Journal Article
ZDB-ID	415519-1
ISSN	1897-4260 ; 0028-3843
ISSN (online)	1897-4260
ISSN	0028-3843
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Article: Role of LGR5-positive mesenchymal cells in craniofacial development.

Olbertová, Kristýna / Hrčkulák, Dušan / Kříž, Vítězslav / Jesionek, Wojciech / Kubovčiak, Jan / Ešner, Milan / Kořínek, Vladimír / Buchtová, Marcela

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 810527

Abstract: Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), a Wnt pathway member, has been previously recognised as a stem cell marker in numerous epithelial tissues. In this study, we ... ...

Abstract	Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), a Wnt pathway member, has been previously recognised as a stem cell marker in numerous epithelial tissues. In this study, we used
Language	English
Publishing date	2022-09-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.810527
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Article ; Online: Glomerular diseases: podocyte hypertrophy mismatch and glomerular disease.

Kriz, Wilhelm

Nature reviews. Nephrology

2012 Volume 8, Issue 11, Page(s) 618–619

MeSH term(s)	Body Weight/physiology ; Glomerular Basement Membrane/pathology ; Glomerular Basement Membrane/physiopathology ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Hypertrophy ; Kidney Diseases/pathology ; Kidney Glomerulus ; Podocytes/pathology
Language	English
Publishing date	2012-09-25
Publishing country	England
Document type	News ; Research Support, Non-U.S. Gov't
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/nrneph.2012.198
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Zs.A 6334: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 107: Show issues

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Article: Hand-Held Echocardiography by Advanced Practice Providers in Patients with Congestive Heart Failure.

Tagle-Cornell, Maria Cecilia / Novais, Barbara S / Wen, Songnan / Shipman, Justin N / Mandale, Deepa R / Flom, Andrew P / Sahnan, Sandeep K / Kriz, Lindsey M / Alland, Michelle L / Bird, Christen W / Naqvi, Tasneem Z

Journal of clinical medicine

2024 Volume 13, Issue 2

Abstract: Objectives: The performed hand-held echocardiography (HHE) was evaluated and interpreted by trained advanced practice providers (APPs) on hospitalized CHF patients for image quality and interpretation by comparing with expert echocardiographer and SE ... ...

Abstract	Objectives: The performed hand-held echocardiography (HHE) was evaluated and interpreted by trained advanced practice providers (APPs) on hospitalized CHF patients for image quality and interpretation by comparing with expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While a standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: (a) left ventricular (LV) size, (b) LV ejection fraction (LVEF), and (c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted the HHE images and compared them with APPs and SE findings. Kappa statistics determined the degree of agreement between APPs and the study echocardiographer's interpretation of the HHE images and SE. Results: A total of 80 CHF patients (age 73 ± 14 years, 58% males; LVEF (by SE) 45 ± 19%; 36.3% body mass indexes ≥ 30 kg/m Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted the LV function and RAP in CHF patients in good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients, leading to expedited and optimized treatment.
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13020312
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Article: QSAR-derived affinity fingerprints (part 1): fingerprint construction and modeling performance for similarity searching, bioactivity classification and scaffold hopping.

Škuta, C / Cortés-Ciriano, I / Dehaen, W / Kříž, P / van Westen, G J P / Tetko, I V / Bender, A / Svozil, D

Journal of cheminformatics

2020 Volume 12, Issue 1, Page(s) 39

Abstract: An affinity fingerprint is the vector consisting of compound's affinity or potency against the reference panel of protein targets. Here, we present the QAFFP fingerprint, 440 elements long in silico QSAR-based affinity fingerprint, components of which ... ...

Abstract	An affinity fingerprint is the vector consisting of compound's affinity or potency against the reference panel of protein targets. Here, we present the QAFFP fingerprint, 440 elements long in silico QSAR-based affinity fingerprint, components of which are predicted by Random Forest regression models trained on bioactivity data from the ChEMBL database. Both real-valued (rv-QAFFP) and binary (b-QAFFP) versions of the QAFFP fingerprint were implemented and their performance in similarity searching, biological activity classification and scaffold hopping was assessed and compared to that of the 1024 bits long Morgan2 fingerprint (the RDKit implementation of the ECFP4 fingerprint). In both similarity searching and biological activity classification, the QAFFP fingerprint yields retrieval rates, measured by AUC (~ 0.65 and ~ 0.70 for similarity searching depending on data sets, and ~ 0.85 for classification) and EF5 (~ 4.67 and ~ 5.82 for similarity searching depending on data sets, and ~ 2.10 for classification), comparable to that of the Morgan2 fingerprint (similarity searching AUC of ~ 0.57 and ~ 0.66, and EF5 of ~ 4.09 and ~ 6.41, depending on data sets, classification AUC of ~ 0.87, and EF5 of ~ 2.16). However, the QAFFP fingerprint outperforms the Morgan2 fingerprint in scaffold hopping as it is able to retrieve 1146 out of existing 1749 scaffolds, while the Morgan2 fingerprint reveals only 864 scaffolds.
Language	English
Publishing date	2020-05-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2486539-4
ISSN	1758-2946
ISSN	1758-2946
DOI	10.1186/s13321-020-00443-6
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Article ; Online: Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome.

Shaik, Shabana M / Cao, Yajun / Gogola, Joseph V / Dodiya, Hemraj B / Zhang, Xulun / Boutej, Hejer / Han, Weinong / Kriz, Jasna / Sisodia, Sangram S

Molecular neurodegeneration

2023 Volume 18, Issue 1, Page(s) 95

Abstract: Background: Microglia, the brain-resident macrophages perform immune surveillance and engage with pathological processes resulting in phenotype changes necessary for maintaining homeostasis. In preceding studies, we showed that antibiotic-induced ... ...

Abstract	Background: Microglia, the brain-resident macrophages perform immune surveillance and engage with pathological processes resulting in phenotype changes necessary for maintaining homeostasis. In preceding studies, we showed that antibiotic-induced perturbations of the gut microbiome of APPPS1-21 mice resulted in significant attenuation in Aβ amyloidosis and altered microglial phenotypes that are specific to male mice. The molecular events underlying microglial phenotypic transitions remain unclear. Here, by generating 'APPPS1-21-CD11br' reporter mice, we investigated the translational state of microglial/macrophage ribosomes during their phenotypic transition and in a sex-specific manner. Methods: Six groups of mice that included WT-CD11br, antibiotic (ABX) or vehicle-treated APPPS1-21-CD11br males and females were sacrificed at 7-weeks of age (n = 15/group) and used for immunoprecipitation of microglial/macrophage polysomes from cortical homogenates using anti-FLAG antibody. Liquid chromatography coupled to tandem mass spectrometry and label-free quantification was used to identify newly synthesized peptides isolated from polysomes. Results: We show that ABX-treatment leads to decreased Aβ levels in male APPPS1-21-CD11br mice with no significant changes in females. We identified microglial/macrophage polypeptides involved in mitochondrial dysfunction and altered calcium signaling that are associated with Aβ-induced oxidative stress. Notably, female mice also showed downregulation of newly-synthesized ribosomal proteins. Furthermore, male mice showed an increase in newly-synthesized polypeptides involved in FcγR-mediated phagocytosis, while females showed an increase in newly-synthesized polypeptides responsible for actin organization associated with microglial activation. Next, we show that ABX-treatment resulted in substantial remodeling of the epigenetic landscape, leading to a metabolic shift that accommodates the increased bioenergetic and biosynthetic demands associated with microglial polarization in a sex-specific manner. While microglia in ABX-treated male mice exhibited a metabolic shift towards a neuroprotective phenotype that promotes Aβ clearance, microglia in ABX-treated female mice exhibited loss of energy homeostasis due to persistent mitochondrial dysfunction and impaired lysosomal clearance that was associated with inflammatory phenotypes. Conclusions: Our studies provide the first snapshot of the translational state of microglial/macrophage cells in a mouse model of Aβ amyloidosis that was subject to ABX treatment. ABX-mediated changes resulted in metabolic reprogramming of microglial phenotypes to modulate immune responses and amyloid clearance in a sex-specific manner. This microglial plasticity to support neuro-energetic homeostasis for its function based on sex paves the path for therapeutic modulation of immunometabolism for neurodegeneration.
MeSH term(s)	Mice ; Animals ; Male ; Female ; Alzheimer Disease/metabolism ; Microglia/metabolism ; Mice, Transgenic ; Anti-Bacterial Agents/metabolism ; Anti-Bacterial Agents/pharmacology ; Amyloidosis/metabolism ; Microbiota ; Macrophages/metabolism ; Peptides/metabolism ; Mitochondrial Diseases/metabolism ; Mitochondrial Diseases/pathology ; Epigenesis, Genetic ; Amyloid beta-Peptides/metabolism ; Disease Models, Animal
Chemical Substances	Anti-Bacterial Agents ; Peptides ; Amyloid beta-Peptides
Language	English
Publishing date	2023-12-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-023-00668-7
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