bluuebunny/crossref_metadata_2025_split huggingface dataset:
„The Gospel Singing (Good People)“
Authors: Sinapius Peter 
Published: April 2021

ZusammenfassungUnter den Stichworten Gesundheit, Kunst und Spiritualität skizziert der Artikel eine Entwicklung in den modernen Gesellschaften, die in den letzten Jahrzehnten eine Kultur der individuellen Gesundheitspflege und Selbstoptimierung hervorgebracht hat, die begleitet wurde von einer Spiritualisierung, Sakralisierung und Ideologisierung therapeutischer Praktiken. Sie verstand sich als Gegenbewegung zur naturwissenschaftlich orientierten Medizin und fand ihre Verwirklichung in holistischen Entwürfen von Gesundheit und alternativen Formen therapeutischer Praxis. Die Kreativität wurde dabei zum Leitmotiv und dem schöpferischen Menschen die Aufgabe zugewiesen, seine Persönlichkeit zu entfalten und ein unverwechselbares Individuum zu werden. Ästhetische Praktiken wurden als ein Übersteigen der sinnlichen Wirklichkeit konzeptualisiert und als Grundbedingung von Erkenntnis und Selbstverwirklichung in der Therapie geltend gemacht.Der Beitrag kommentiert diese Entwicklung kritisch und entwirft dagegen ein Therapieverständnis, das die Therapie als einen Ort auffasst, an dem unterschiedliche Lebenskonzepte oder -entwürfe thematisch werden können. Künstlerische Praktiken sind dabei eine Möglichkeit unter anderen, durch die das geschehen kann. Sinn verwirklicht sich dann in der Art und Weise, wie die Beteiligten sich selber und andere sehen, wie sie sich zu anderen und zu anderem in eine Beziehung bringen und in dem Umfang, wie sie einen (kritischen) Blick auf ihre und andere Einstellungen und Vorstellungen gewinnen.
Metastatic medullary thyroid carcinoma presenting as ectopic Cushing’s syndrome
Authors: Forde Hannah E , Mehigan-Farrelly Niamh , Ryan Katie , Moran Tom , Greally Megan , Duffy Austin G , Byrne Maria M 
Published: April 2021

Summary
A 41-year-old male presented to the Emergency Department with a 6-month history of back and hip pain. Skeletal survey revealed bilateral pubic rami fractures and MRI of the spine demonstrated multiple thoracic and lumbar fractures. Secondary work up for osteoporosis was undertaken. There was no evidence of hyperparathyroidism and the patient was vitamin D replete. Testosterone (T) was low at 1.7 nmol/L (8.6–29.0) and gonadotrophins were undetectable. The patient failed a 1 mg dexamethasone suppression test (DST) with a morning cortisol of 570 nmol/L (<50) and subsequently a low dose DST with a cortisol post 48 h of dexamethasone of 773 nmol/L (<50) and an elevated ACTH 98 ng/L. A corticotropin-releasing factor (CRF) test suggested ectopic ACTH secretion. The patient was commenced on teriparatide for osteoporosis and metyrapone to control the hypercortisolaemia. A positron emission tomography (PET) scan to look for the source of ACTH secretion demonstrated right neck adenopathy. Biopsy and subsequent lymph node dissection were performed and histology revealed a metastatic neuroendocrine tumour. Immunostaining was positive for calcitonin and thyroid transcription factor 1 (TTF1). Serum calcitonin was also significantly elevated at 45 264 ng/L (<10). The patient proceeded to a total thyroidectomy and left neck dissection. Histology confirmed a 7 mm medullary thyroid carcinoma (MTC). Post-operatively, the patient commenced vandetanib therapy and achieved a clinical and biochemical response. After approximately 18 months of vandetanib therapy, the patient developed recurrent disease in his neck. He is currently on LOXO-292 and is doing well 36 months post-diagnosis.

Learning points

Unexplained osteoporosis requires thorough investigation and the workup for secondary causes is not complete without excluding glucocorticoid excess.

MTC should be considered when searching for sources of ectopic ACTH secretion.

Resistance to tyrosine kinase inhibitors is well described with MTC and clinicians should have a low threshold for screening for recurrent disease.
Tratamiento de mixoma odontogénico en maxilar superior. Reporte de un caso
Authors: Moreno Villalobos David Erik , Rodríguez Flores Arturo , Vargas Rojas Diana Carolina 
Published: April 2021

El mixoma odontogénico es una neoplasia benigna, localmente agresiva, con una baja prevalencia (frecuencia del 2% al 5% de los tumores odontogénicos) en los maxilares. Este tumor a menudo se presenta como una lesión expansiva asintomática sin cambios nerviosos sensoriales. El objetivo del presente trabajo es detallar el caso de un paciente masculino de 42 años quien acude al servicio de Cirugía Bucal y Maxilofacial del Hospital Nacional Hipólito Unanue por presentar una tumoración de crecimiento lento en maxilar superior, que fue aumentando de tamaño con el tiempo y desplazando órganos dentarios, y que se extiende al paladar duro y parte de paladar blando, el diagnóstico anatomopatológico fue de mixoma odontogénico y recibió un tratamiento radical (hemimaxilectomia) por la naturaleza agresiva del tumor. En este trabajo discutimos la presentación del mixoma odontogénico en el maxilar superior, los enfoques de tratamiento; detallando la importancia de plantear alternativas de tratamiento que permitan la reconstrucción inmediata generando la menor morbilidad posible.
Role of Ras Isoforms in the Stimulated Proliferation of Human Renal Fibroblasts in Primary Culture
Authors: SHARPE CLAIRE C. , DOCKRELL MARK E. C. , NOOR MAZHAR I. , MONIA BRETT P. , HENDRY BRUCE M. 
Published: April 2021

Abstract.
The proliferation of renal fibroblasts is implicated in the pathophysiologic processes of renal fibrosis. Many of the growth factors involved in proliferation are known to activate intracellular signaling pathways that converge on Ras monomeric GTPases. Although three ras family genes exist, their functional specificity is not yet known. Using antisense oligonucleotides, a role for Kirsten (Ki)-Ras in the stimulated proliferation of a primate renal fibroblast cell line was previously demonstrated. This study examines Ras in primary cultures of adult human renal fibroblasts. Using reverse transcription-PCR, mRNA for Harvey (Ha)-ras, Ki(4B)-ras, and neural (N)-ras, but not Ki(4A)-ras, were detected. Antisense oligonucleotides targeting Ha-, Ki-, and N-ras mRNA, which were used for liposomal transfection at 100 to 200 nM, were demonstrated to be active and isoform-specific in quantitative reverse transcription-PCR assays. Cellular Ras protein levels, as estimated using isoform-specific monoclonal antibodies, indicated that Ki-Ras was the predominantly expressed isoform (>95% of total Ras protein) under both serum-containing and serum-free conditions, with N- and Ha-Ras being detected in small amounts. Consistent with this finding, the antisense oligonucleotide directed against Ki-Ras reduced total cellular Ras levels by >70%, whereas Ha-Ras, N-Ras, and control oligonucleotides had no significant effect. Proliferation of oligonucleotide-transfected cells was measured using epidermal growth factor (EGF) and serum stimulation. The Ki-Ras oligonucleotide at 100 nM reduced serum-stimulated proliferation by >50% and EGF-stimulated proliferation by 25%, compared with data obtained with the control oligonucleotide (P < 0.01). The N-Ras oligonucleotide was not active, compared with the control oligonucleotide. The Ha-Ras oligonucleotide was not significantly active at 100 nM but reduced serum-stimulated proliferation by 13% and EGF-stimulated growth by 40% at 200 nM (P < 0.01). These results demonstrate that Ki-Ras(4B) is the predominantly expressed Ras isoform in human renal fibroblasts in primary culture and is important for both serum- and EGF-stimulated proliferation. Ha-Ras appears to be expressed at low levels but may also play a distinct role in stimulated proliferation.
Abnormal Glomerular Basement Membrane Laminins in Murine, Canine, and Human Alport Syndrome
Authors: KASHTAN CLIFFORD E. , KIM YOUNGKI , LEES GEORGE E. , THORNER PAUL S. , VIRTANEN ISMO , MINER JEFFREY H. 
Published: April 2021

Abstract.
Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin α, β, and γ chains using monospecific antibodies. Laminin α2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin α2 seems to be deposited as part of both laminin-2 (α2β1γ1) and laminin-4 (α2β2γ1) but as part of only laminin-4 in human Alport kidneys. GBM laminin α2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the α3, α4, and α5 chains of type IV collagen: (1) type IV collagen α1 and α2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin α2 chain and (5) the laminin α1 and β1 chains in mice and dogs. These findings emphasize further the critical role played by the α3, α4, and α5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.
Expression of Apoptosis-Related Genes and Proteins in Experimental Chronic Renal Scarring
Authors: YANG BIN , JOHNSON TIMOTHY S. , THOMAS GRAHAM L. , WATSON PHILIP F. , WAGNER BART , SKILL NICHOLAS J. , HAYLOR JOHN L. , NAHAS A. MEGUID EL 
Published: April 2021

Abstract.
Apoptosis has been proposed to play an important role in the progression of renal scarring. The mechanisms that determine whether a cell enters the apoptotic program are complex. Bax and Bcl-2 are recognized modulators of this event; their relative levels determine the fate of cells. A role for apoptosis in the progression of renal scarring in the remnant kidneys of rats submitted to subtotal nephrectomy (SNx) has been described. This study investigated the expression (protein and mRNA) of Bax and Bcl-2 in remnant kidneys between day 7 and day 120 post-SNx. Northern blot analysis showed that bax mRNA was increased in remnant kidneys from day 7 (150% of control; P < 0.05), whereas bcl-2 mRNA was decreased from day 15 (23% of control; P < 0.05) resulting in a 14-fold increase in the ratio of bax to bcl-2 mRNA by day 120. Western blot analysis showed similar changes in Bax and Bcl-2 protein in remnant kidneys, resulting in a 147-fold increase in the ratio of Bax to Bcl-2 on day 120. Immunohistochemistry showed increases in Bax to be located predominantly in tubules in SNx kidneys. Interstingly, Bcl-2 immunostaining increased in some epithelial cells within atrophic tubules despite the overall decrease in Bcl-2 protein and mRNA. The overall renal apoptotic cells correlated closely with the ratio of bax to bcl-2 at both the mRNA and protein levels (r = 0.594 and 0.308, respectively; P < 0.05). Furthermore, tubular apoptosis correlated positively with the mRNA level of bax (r = 0.471; P < 0.01) and negatively with the mRNA and protein levels of bcl-2 (r = -0.443 and -0.607, respectively; P < 0.01). The increase in the ratio of the death inducer (Bax) to the death repressor (Bcl-2) at the mRNA and protein levels may control the apoptosis associated with the progression of tubular atrophy and chronic renal fibrosis within remnant rat kidneys. These observations may have prognostic and therapeutic implications in chronic renal failure.
Trends of Analgesic Nephropathy in Two High-Endemic Regions with Different Legislation
Authors: MICHIELSEN PAUL , SCHEPPER PAUL DE 
Published: April 2021

Abstract.
Analgesic abuse is related to a specific form of interstitial nephritis, but the exact nature of the causal agent remains controversial and this has resulted in differences in regulation. In Flanders, the free sale of phenacetin was banned, but the consumption of other combined analgesics remained free. In New South Wales, phenacetin was also banned, but 2 yr later the sales of all combined analgesics were also prohibited. This study compared the evolution of end-stage renal disease as a result of analgesic nephropathy (AN) in these two high-endemic regions with different legislation. In both regions, the time trend of the age-specific incidence of end-stage renal disease as a result of AN is similar in the age group 45 to 54 yr. In all age groups combined, the time trend of the percentage of AN among the patients admitted for renal replacement therapy is also similar. This finding does not support the hypothesis that non-phenacetin mixed analgesics play a significant role in the occurrence of AN.
Angiotensinogen in Essential Hypertension
Authors: LALOUEL JEAN-MARC , ROHRWASSER ANDREAS , TERREROS DANIEL , MORGAN TERRY , WARD KENNETH 
Published: April 2021

Abstract.
There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.
Transcytosis of Retinol-Binding Protein across Renal Proximal Tubule Cells after Megalin (gp 330)-Mediated Endocytosis
Authors: MARINÓ MICHELE , ANDREWS DAVID , BROWN DENNIS , McCLUSKEY ROBERT T. 
Published: April 2021

Abstract.
Plasma retinol-binding protein (RBP) combined with vitamin A (retinol) is partially filtered through the glomerulus and then absorbed by proximal tubule cells, leading to recycling of retinol to the circulation. Recently, it was shown that reabsorption of RBP-retinol complexes by proximal tubule cells is mediated by megalin (gp 330), an apical endocytic receptor. It was proposed that RBP is transported by megalin to lysosomes, where it is degraded, thus liberating retinol, which then combines with newly synthesized RBP to be secreted into the bloodstream. This study shows that passage of RBP through immortalized rat renal proximal tubule (IRPT) cells occurs by transcytosis after megalin-mediated endocytosis, which provides an alternative pathway for recycling of retinol. IRPT cells cultured as polarized monolayers with tight junctions were used on permeable filters in the upper chamber of dual-chambered devices, with megalin expression exclusively on the upper surface. After addition of RBP to the upper chamber and incubation at 37°C, intact RBP was found in fluids that were collected from the lower chamber. In contrast, control substances (mannitol, lysozyme, albumin, and glutathione-S-transferase) were not appreciably transported across IRPT cells, indicating that passage of RBP was by transcytosis and not by paracellular leakage. Confocal microscopy analysis of IRPT cells after addition of RBP to the upper chamber revealed RBP-containing granules at the apical membrane, subapically, and also at basolateral membranes. When RBP was added to IRPT cells together with megalin competitors, the amount of transcytosed RBP was markedly reduced. We also found that some RBP was internalized and degraded by IRPT cells, but this process was not appreciably affected by megalin competitors, indicating that RBP endocytosed by megalin was not transported to lysosomes and degraded but rather transcytosed across IRPT cells.
Upregulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor α in Rat Kidney with Ischemia-Reperfusion Injury
Authors: YANG CHUL WOO , LIM SUN WOO , HAN KI WHAN , AHN HEE JONG , PARK JUNG HEE , KIM YOUNG HEE , KIRSH MATTHIAS , CHA JUNG HO , PARK JOO HYUN , KIM YONG SOO , KIM JIN , BANG BYUNG KEE 
Published: April 2021

Abstract.
Ciliary neurotrophic factor (CNTF) is presumed to play a role as a survival factor in neuronal cells, but little is known about its role in the kidney. To investigate this, the expression of CNTF and CNTF receptor α (CNTFR α) was analyzed in the ischemic rat kidney. An ischemia/reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min. Animals were killed at 1, 2, 3, 5, 7, 14, and 28 d after ischemia. The expression of CNTF and CNTFR α was monitored by reverse transcription-PCR, in situ hybridization, immunoblotting, immunohistochemistry, and electron microscopy. In sham-operated rat kidneys, CNTF expression was weak and limited to the descending thin limb of the loop of Henle. With I/R injury, CNTF mRNA and protein expressions were strikingly increased as compared with the sham-operated rat kidney, and the immunoreactivity of CNTF was mainly observed in the regenerating proximal tubules. The expression of CNTFR α mRNA was also increased after I/R injury, and its location and expression patterns were similar to the expression of CNTF. These findings suggest a possible role of CNTF as a growth factor during renal tubular repair processes after I/R injury and an autocrine or paracrine function of CNTF acting against CNTFR α.
Puromycin Aminonucleoside Suppresses Integrin Expression in Cultured Glomerular Epithelial Cells
Authors: KRISHNAMURTI UMA , ZHOU BING , FAN WEI-WEI , TSILIBARY EFFIE , WAYNER ELIZABETH , KIM YOUNGKI , KASHTAN CLIFFORD E. , MICHAEL ALFRED 
Published: April 2021

Abstract.
Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. Because PAN injection into rats results in retraction of glomerular epithelial cell foot processes and glomerular epithelial cell detachment, it was hypothesized that PAN might alter the contacts between these cells and the glomerular basement membrane. The major integrin expressed by glomerular epithelial cells is α3β1, which mediates attachment of these cells to extracellular matrix proteins including type IV collagen. T-SV 40 immortalized human glomerular epithelial cells were used to study PAN's effects on α3β1 expression, as well as that of podocalyxin and the slit diaphragm component ZO-1. Glomerular epithelial cells were seeded into plastic flasks and allowed to attach and proliferate for 48 h. The cells were then incubated for another 48 h in media containing 0, 0.5, or 5.0 μg/ml PAN. PAN exposure resulted in dose-dependent decreases in α3 and β1 expression, both at the protein level and at the mRNA level. This was accompanied by a significant decrease in the adhesion of glomerular epithelial cells to type IV collagen. PAN did not affect ZO-1 protein expression. Treatment with PAN increased the expression of podocalyxin at the protein and mRNA levels. Reduced glomerular epithelial cell expression of α3β1 integrins and impaired adhesion to type IV collagen may contribute to the glomerular epithelial cell detachment from glomerular basement membrane seen in the PAN nephrosis model.
Approaching the Therapeutic Window for Cyclosporine in Kidney Transplantation
Authors: MAHALATI KAMRAN , BELITSKY PHILIP , WEST KENNETH , KIBERD BRYCE , FRASER ALBERT , SKETRIS INGRID , MACDONALD ALAN S. , MCALISTER VIVIAN , LAWEN JOSEPH 
Published: April 2021

Abstract.
Neoral dosing is traditionally based on cyclosporine (CyA) trough levels (C0). Four-h area under the curve (AUC0-4) for Neoral in the early posttransplantation period was shown previously to have a better correlation to acute rejection (AR) and CyA nephrotoxicity (CyANT), compared with C0. An AUC0-4 range of 4400 to 5500 μg/h per L during the first week was associated with the lowest AR and CyANT. This article describes a prospective study to assess the feasibility, safety, and efficacy of dosing Neoral solely by AUC0-4 monitoring, regardless of C0, in the first 3 mo after kidney transplantation. Fifty-nine kidney transplant recipients received Neoral-based triple immunosuppression. AUC0-4 was measured on days 3, 5, 7, 10, and 14 and weeks 3, 4, 6, and 8, then monthly. Target AUC0-4 was 4400 to 5500 μg/h per L. Dose was adjusted by percentage difference from target AUC0-4. Ninety-four percent of AUC were performed on the scheduled day or close to it. No patients had CyANT while AUC0-4 was in target range. Four patients had reversible CyANT with AUC0-4 > 5500. Only 1 of 33 patients (3%) who achieved and maintained AUC0-4 > 4400 by day 3 posttransplantation had AR, whereas 10 of 22 (45%) of those with day 3 to 5 AUC0-4 < 4400 had AR (P = 0.0002). In logistic regression analysis, higher early AUC0-4 was the only significant variable associated with lower serum creatinine at 3 mo. Neoral dose monitoring by AUC0-4 is a potentially valuable tool for optimizing Neoral immunosuppression. Attainment of a target range of 4400 to 5500 μg/h per L for AUC0-4 early after transplantation has been demonstrated to reduce significantly the risk of AR and CyANT.
Polycystin
Authors: WILSON PATRICIA D. 
Published: April 2021

Abstract.
Polycystin-1 is a modular membrane protein with a long extracellular N-terminal portion that bears several ligand-binding domains, 11 transmembrane domains, and a ≥200 amino acid intracellular C-terminal portion with several phosphorylation signaling sites. Polycystin-1 is highly expressed in the basal membranes of ureteric bud epithelia during early development of the metanephric kidney, and disruption of the PKD1 gene in mice leads to cystic kidneys and embryonic or perinatal death. It is proposed that polycystin-1 functions as a matrix receptor to link the extracellular matrix to the actin cytoskeleton via focal adhesion proteins. Co-localization, co-sedimentation, and co-immunoprecipitation studies show that polycystin-1 forms multiprotein complexes with α2β1-integrin, talin, vinculin, paxillin, p130cas, focal adhesion kinase, and c-src in normal human fetal collecting tubules and sub-confluent epithelial cultures. In normal adult kidneys and confluent epithelial cultures, polycystin-1 is downregulated and forms complexes with the cell-cell adherens junction proteins E-cadherin and β-, γ-, and α-catenin. Polycystin-1 activation at the cell membrane leads to intracellular signaling via phosphorylation through the c-Jun terminal kinase and wnt pathways leading to activation of AP-1 and TCF/LEF-dependent genes, respectively. The C-terminal of polcystin-1 has been shown to be phosphorylated by c-src at Y4237, by protein kinase A at S4252, and by focal adhesion kinase and protein kinase X at yet-to-be identified residues. Inhibition of tyrosine phosphorylation or increased cellular calcium increases polycystin-1 focal adhesion complexes versus polycystin-1 adherens junction complexes, whereas disruption of the actin cytoskeleton dissociates all polycystin-1 complexes. Genetic evidence suggests that PKD1, PKD2, NPHP1, and tensin are in the same pathway.