scholarly journals Growth hormone and Klotho

2013 ◽  
Vol 219 (2) ◽  
pp. R37-R57 ◽  
Author(s):  
Christoph Schmid ◽  
Marian C Neidert ◽  
Oliver Tschopp ◽  
Lisa Sze ◽  
René L Bernays
Keyword(s):  
Transmembrane Protein ◽  
Fibroblast Growth Factor 23 ◽  
Distal Tubule ◽  
Suppressor Gene ◽  
Signalling Pathways ◽  
Renal Phosphate Reabsorption ◽  
Pituitary Glands ◽  
Predominant Expression

Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data suggest that soluble Klotho (sKlotho) is also elevated in patients with active acromegaly. sKlotho decreases towards normal following removal of the GH-producing pituitary adenoma. TheKlothogene was identified in mice following its accidental disruption by ectopic DNA. It is an ageing suppressor gene of restricted expression (mainly in kidneys, brain, and parathyroid and pituitary glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co-receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes urinary phosphate excretion and inhibits the synthesis of calcitriol. The ectodomain of mKlotho is enzymatically released to result in a humoral factor, sKlotho, which exerts systemic effects (on ion channels and signalling pathways), possibly by working as an enzyme that modifies glycans of cell surface glycoproteins. GH enhances renal phosphate reabsorption and calcitriol production, i.e. exerts effects in the proximal tubule opposing those attributed to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho. sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in kidneys and choroid plexus, concentrations of sKlotho are particularly high in urine and CSF. Determination of sKlotho in serum and urine (both presumably reflecting GH action on the kidneys) could be used as a supplementary tool in the diagnosis and follow-up of patients with acromegaly. The question arises whether GH exerts selected actions via modifying activities of Klotho.

EVALUASI KESESUAIAN PELAKSANAAN PROBITY AUDIT PADA BPKP PUSAT DENGAN PEDOMAN PROBITY AUDIT PENGADAAN BARANG/JASA PEMERINTAH

INFO ARTHA ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 17-34
Author(s):  
Fadlil Usman
Keyword(s):  
Public Sector ◽  
Real Time ◽  
Procurement Process ◽  
Assessment Activity

Probity audit is an independence assessment activity to ensure the goods/services procurement processes have been implemented consistently appropriate with the principle of upholding integrity, uprightness, honesty and fulfill certain occur legislation aimed for improving the accountability for the use of public sector fund. Probity audit is done in real time simultaneously with the goods/services procurement process. This study aims to evaluate the suitability of the implementation of probity audit conducted by BPKP Headquarter as agency that initiated the implementation of probity audit in Indonesia compared with the Probity audit Guidelines for Procurement of Goods/Services as criteria. The results of this study indicate that the implementation of probity audit conducted by BPKP Headquarter has been implemented adequately, but there are activities that do not fit the criteria, especially in the activities of the determination of the scope of the audit, the preparation of working papers and the follow-up monitoring of the audit results. Probity audit merupakan kegiatan penilaian (independen) untuk memastikan bahwa proses pengadaan barang/jasa telah dilaksanakan secara konsisten sesuai dengan prinsip penegakan integritas, kebenaran, kejujuran dan memenuhi ketentuan perundangan yang berlaku yang bertujuan meningkatkan akuntabilitas penggunaan dana sektor publik. Probity audit dilakukan secara real time yaitu bersamaan dengan pelaksanaan pengadaan barang/jasa. Penelitian ini bertujuan untuk melakukan evaluasi kesesuaian pelaksanaan probity audit yang dilakukan oleh BPKP Pusat selaku instansi yang menginisiasi pelaksanaan probity audit di Indonesia dibandingkan dengan kriteria berupa Pedoman Probity audit Pengadaan Barang/Jasa Pemerintah. Hasil dari penelitian ini menunjukkan bahwa pelaksanaan probity audit yang dilakukan oleh BPKP Pusat sudah dilaksanakan secara memadai, namun masih terdapat hal yang belum sesuai dengan kriteria terutama dalam kegiatan penentuan ruang lingkup audit, penyusunan kertas kerja dan pemantauan terhadap tindak lanjut hasil audit.

scholarly journals Pathophysiological In Vitro Profile of Neuronal Differentiated Cells Derived from Niemann-Pick Disease Type C2 Patient-Specific iPSCs Carrying the NPC2 Mutations c.58G>T/c.140G>T

2021 ◽  
Vol 22 (8) ◽  
pp. 4009
Author(s):  
Maik Liedtke ◽  
Christin Völkner ◽  
Alexandra V. Jürs ◽  
Franziska Peter ◽  
Michael Rabenstein ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transmembrane Protein ◽  
Hereditary Disease ◽  
Cholesterol Homeostasis ◽  
Patient Specific ◽  
Differentiated Cells ◽  
Npc1 Gene ◽  
Niemann Pick

Niemann-Pick type C2 (NP-C2) disease is a rare hereditary disease caused by mutations in the NPC2 gene. NPC2 is a small, soluble protein consisting of 151 amino acids, primarily expressed in late endosomes and lysosomes (LE/LY). Together with NPC1, a transmembrane protein found in these organelles, NPC2 accomplishes the exclusion of cholesterol; thus, both proteins are essential to maintain cellular cholesterol homeostasis. Consequently, mutations in the NPC2 or NPC1 gene result in pathophysiological accumulation of cholesterol and sphingolipids in LE/LY. The vast majority of Niemann-Pick type C disease patients, 95%, suffer from a mutation of NPC1, and only 5% display a mutation of NPC2. The biochemical phenotype of NP-C1 and NP-C2 appears to be indistinguishable, and both diseases share several commonalities in the clinical manifestation. Studies of the pathological mechanisms underlying NP-C2 are mostly based on NP-C2 animal models and NP-C2 patient-derived fibroblasts. Recently, we established induced pluripotent stem cells (iPSCs), derived from a donor carrying the NPC2 mutations c.58G>T/c.140G>T. Here, we present a profile of pathophysiological in vitro features, shared by NP-C1 and NP-C2, of neural differentiated cells obtained from the patient specific iPSCs. Profiling comprised a determination of the NPC2 protein level, detection of cholesterol accumulation by filipin staining, analysis of oxidative stress, and determination of autophagy. As expected, the NPC2-deficient cells displayed a significantly reduced amount of NPC2 protein, and, accordingly, we observed a significantly increased amount of cholesterol. Most notably, NPC2-deficient cells displayed only a slight increase of reactive oxygen species (ROS), suggesting that they do not suffer from oxidative stress and express catalase at a high level. As a site note, comparable NPC1-deficient cells suffer from a lack of catalase and display an increased level of ROS. In summary, this cell line provides a valuable tool to gain deeper understanding, not only of the pathogenic mechanism of NP-C2, but also of NP-C1.

Squamous Cell Carcinoma of the External Ear: A Review of 75 Cases

1987 ◽  
Vol 97 (3) ◽  
pp. 308-312 ◽  
Author(s):  
William W. Shockley ◽  
Fred J. Stucker
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cancer Control ◽  
Surgical Excision ◽  
External Ear ◽  
Common Cancer ◽  
Node Metastases

Squamous cell carcinoma of the external ear can be a potentially lethal lesion. Although it is the most common cancer involving the pinna, the variables that have the greatest impact on prognosis are still in question. We reviewed 75 cases of squamous cell carcinoma of the external ear to determine patterns of occurrence and treatment failure. Forty patients had adequate follow-up for determination of cancer control rates. Local control was successful with initial treatment in 85% of the cases. The incidence of lymph node metastases was 10%, whereas distant metastasis occurred in only one patient (2.5%). This series differs from others in that most patients were unselected and most of the lesions treated were early (less than 1 cm). The significance of positive margins after surgical excision is also analyzed.

scholarly journals Determination of Transmembrane Protein with Diazotized (125I)-Iodosulfanilic Acid in the Squid Giant Axon

1978 ◽  
Vol 54 (6) ◽  
pp. 310-315 ◽  
Author(s):  
Tohru YOSHIOKA ◽  
Toshifumi TAKENAKA ◽  
Hidenori HORIE ◽  
Hiroko INOUE ◽  
Kimie INOMATA
Keyword(s):  
Transmembrane Protein ◽  
Giant Axon ◽  
Squid Giant Axon

scholarly journals Cervical Cat Scratch Disease Lymphadenitis in a Patient with Immunoglobulin M Antibodies to Toxoplasma gondii

2002 ◽  
Vol 9 (2) ◽  
pp. 496-498
Author(s):  
Mardjan Arvand ◽  
Ilkay Kazak ◽  
Sergije Jovanovic ◽  
Hans-Dieter Foss ◽  
Oliver Liesenfeld
Keyword(s):  
Toxoplasma Gondii ◽  
Clinical Symptoms ◽  
Bartonella Henselae ◽  
Cervical Lymphadenopathy ◽  
Immunoglobulin M ◽  
Cat Scratch Disease ◽  
Specific Immunoglobulin ◽  
Acute Toxoplasmosis

ABSTRACT We report on a young patient with chronic cervical lymphadenopathy and serological and histological evidence for infection with Bartonella henselae and Toxoplasma gondii. Serological follow-up studies, including testing for avidity of Toxoplasma-specific immunoglobulin G antibodies, assisted in the determination of the cause of the acute lymphadenitis. Our results suggest that the clinical symptoms were most likely due to cat scratch disease rather than to acute toxoplasmosis.

Effectiveness of a Modified Version of Airflow Therapy

1982 ◽  
Vol 47 (2) ◽  
pp. 160-164
Author(s):  
Glenn L. Falkowski ◽  
Arthur M. Guilford ◽  
Jack Sandler
Keyword(s):  
Success Rate ◽  
Scientific Literature ◽  
Future Research ◽  
Relative Importance ◽  
Differential Effectiveness ◽  
History Of ◽  
One Year ◽  
Main Components

Utilizing airflow therapy, Schwartz (1976) has claimed an 89% success rate with stutterers following treatment and an 83% success rate at one year follow-up. Such claims have yet to be documented in the scientific literature. The purposes of this study were: (a) to investigate the effectiveness of a modified version of airflow therapy; (b) to examine the relative importance of its two main components—passive airflow and elongation of the first vowel spoken. The speech of two adult male stutterers with a lengthy history of stuttering, was assessed with spontaneous speaking and reading tasks. Results indicated marked improvement in both subjects' speech on the reading task was maintained at follow-up 10 weeks later. For spontaneous speech, results were generally weaker and less durable. Effects of the two treatment components were cumulative and did not allow determination of any differential effectiveness between components. Implications of these findings were considered and directions for future research discussed.

Anticholinergic Medication Use, Dopaminergic Genotype, and Recurrent Falls

2021 ◽  
Author(s):  
Andrea L Rosso ◽  
Zachary A Marcum ◽  
Xiaonan Zhu ◽  
Nicolaas Bohnen ◽  
Caterina Rosano
Keyword(s):  
Fall Risk ◽  
Medication Use ◽  
Effect Modification ◽  
Anticholinergic Medication ◽  
Anticholinergic Medications ◽  
Recurrent Falls ◽  
Health Aging ◽  
Dopamine Signaling

Abstract Background Anticholinergic medications are associated with fall risk. Higher dopaminergic signaling may provide resilience to these effects. We tested interactions between anticholinergic medication use and dopaminergic genotype on risk for recurrent falls over 10 years. Methods Participants in the Health, Aging, and Body Composition (Health ABC) study (n = 2 372, mean age = 73.6; 47.8% men; 60.0% White) without disability or anticholinergic use at baseline were followed for up to 10 years for falls. Medication use was documented in 7 of 10 years. Highly anticholinergic medications were defined by Beers criteria, 2019. Recurrent falls were defined as ≥2 in the 12 months following medication assessment. Generalized estimating equations tested the association of anticholinergic use with recurrent falls in the following 12 months, adjusted for demographics, health characteristics, and anticholinergic use indicators. Effect modification by dopaminergic genotype (catechol-O-methyltransferase [COMT]; Met/Met, higher dopamine signaling, n = 454 vs Val carriers, lower dopamine signaling, n = 1 918) was tested and analyses repeated stratified by genotype. Results During follow-up, 841 people reported recurrent falls. Anticholinergic use doubled the odds of recurrent falls (adjusted odds ratio [OR] [95% CI] = 2.09 [1.45, 3.03]), with suggested effect modification by COMT (p = .1). The association was present in Val carriers (adjusted OR [95% CI] = 2.16 [1.44, 3.23]), but not in Met/Met genotype (adjusted OR [95% CI] = 1.70 [0.66, 4.41]). Effect sizes were stronger when excluding baseline recurrent fallers. Conclusion Higher dopaminergic signaling may provide protection against increased 12-month fall risk from anticholinergic use. Assessing vulnerability to the adverse effects of anticholinergic medications could help in determination of risk/benefit ratio for prescribing and deprescribing anticholinergics in older adults.

Determination of Dynamic Limits for Rig Heave and Running Speed Based on Drilling Parameters, Well Data and Completion Tool Limitations - Case Studies

2021 ◽  
Author(s):  
Dmitri Gorski ◽  
Martin Kvernland ◽  
Knut Hals ◽  
Margrethe Blaaflat ◽  
Johannes Ladenhauf ◽  
...  
Keyword(s):  
Drill Pipe ◽  
Planning Software ◽  
Drilling Parameters ◽  
Industry Practice ◽  
Novel Method ◽  
Different Depths ◽  
Well Data ◽  
Productive Time

Summary A novel method of utilizing simulations of surge and swab induced by floating rig heave is presented in this paper. The intended applications are in well planning and follow-up of drilling and completion operations. We focus on rig heave during drill pipe connections when the rig's heave compensator cannot be engaged. The method consists of: (1) estimating a dynamic, well- and operation-specific, rig heave limit based on surge & swab simulations at different depths in a well and (2) clearly communicating the dynamic rig heave limit to the rig crew and onshore organization as a simple metric. We present cases where this novel methodology has been tested during the drilling and completion of two offshore wells in Norway, and we elaborate on the operators’ view of the method's advantages. We conclude that complementing the traditional fixed rig-specific heave limit with the dynamic one that is based on the properties of the actual well and the actual drilling/completion parameters offers an opportunity to improve management of risks related to breaching well pressure margins or damaging downhole equipment and to reduce costs through reduction of weather-related non-productive time. We show that the dynamic rig heave limit may differ significantly from well to well and also throughout the same well depending on the kind of operation in the well, depth in the well, well geometry and other parameters related to well and operation properties. Our conclusion is that care should be taken when generalizing a maximum allowed rig heave value as is the industry practice today. The benefits of utilizing dynamic well-specific rig heave limit should be assessed during well planning for any well drilled and completed from a floating rig. Well planning software existing today does not offer this functionality.

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