Biomedical subjects

Joris H Robben

Publications and source records attributed to Joris H Robben.

4 recordsLinked to original sources

PubMed2006

Polarisation, key to good localisation.

Polarisation of cells is crucial for vectorial transport of ions and solutes. In literature, however, proteins specifically targeted to the apical or basolateral membrane are often studied in non-polarised cells. To investigate whether these data can be extrapolated to expression in polarised cells, we studied several membrane-specific proteins. In polarised MDCK cells, the Aquaporin-2 water channel resides in intracellular vesicles and apical membrane, while the vasopressin-type 2 receptor, anion-exchanger 1 (AE1) protein and E-Cadherin mainly localise to the basolateral membrane. In non-polarised MDCK cells, however, Aquaporin-2 localises, besides plasma membrane, mainly in the Golgi complex, while the others show a dispersed staining throughout the cell. Moreover, while AQP2 mutants in dominant nephrogenic diabetes insipidus are missorted to different organelles in polarised cells, they all predominantly localise to the Golgi complex in non-polarised MDCK cells. Additionally, the maturation of V2R, and likely its missorting, is affected in transiently-transfected compared to stably-transfected cells. In conclusion, we show that the use of stably-transfected polarised cells is crucial in interpreting the processing and the localisation of membrane targeted proteins.

Animals↗

PubMed2006

Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.

In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. The disorder nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate pro-urine in response to AVP, which is mostly acquired due to electrolyte disturbances or lithium therapy. Alternatively, NDI is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.

Amino Acid Sequence↗

PubMedDate not supplied

Comparison of ultrasonography, computed tomography, and single-photon emission computed tomography for the detection and localization of canine insulinoma.

Accurate preoperative detection, localization, and staging of the primary tumor and metastases are essential for the selection of appropriate candidates for surgery. In dogs with insulinoma, preoperative assessment usually is performed with transabdominal ultrasonography (US). There are no reports on the use of computed tomography (CT) for this purpose. The preoperative use of somatostatin receptor scintigraphy (SRS) recently has been advocated for the identification of insulinoma and gastrinoma in dogs, but its accuracy remains to be established. In this report US, CT, and single-photon emission computed tomography (SPECT) with [111In-DTPA-D-Phe1]-octreotide (a specific form of SRS) were compared for their effectiveness in detecting and localizing primary and metastatic insulinoma in dogs. Findings at surgery or postmortem examination served as control. Of 14 primary insulinomas, 5, 10, and 6 were correctly identified by US, CT, and SPECT, respectively. No lymph node metastases were detected by US or SPECT. CT identified 2 of 5 lymph node metastases but also identified 28 false-positive lesions. Two of 4 livers were found to be positive for metastases by 1 of the imaging techniques. US can be used for the initial evaluation of dogs with hypoglycemia. Although CT identifies most primary tumors, intraoperative inspection and palpation of the pancreas is still superior. SPECT appears as effective as US and CT in detecting insulinomas. Future developments in preoperative imaging techniques might improve current methods of canine insulinoma detection.

Animals↗

PubMedDate not supplied

Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism.

In dogs with primary hypoadrenocorticism, hypocortisolism and hypoaldosteronism usually are present, but these deficiencies also may occur in isolated forms. The diagnosis is commonly made by measuring plasma cortisol concentration before and after stimulation with ACTH, thereby ignoring aldosterone. In search of an alternative approach that would include assessment of glucocorticoid and mineralocorticoid production, 2 pairs of endocrine variables were measured: (1) plasma concentration of cortisol and ACTH, and (2) plasma aldosterone concentration and plasma renin activity. In addition, the cortisol-to-ACTH ratio (CAR) and the aldosterone-to-renin ratio (ARR) were calculated. Reference intervals were established in a population of 60 healthy dogs. In these dogs, CAR ranged from 1.1 to 26.1 and ARR ranged from 0.1 to 1.5. The variables were compared with those of 22 dogs with spontaneous primary hypoadrenocorticism. Plasma concentration of cortisol and ACTH in both groups of dogs overlapped, whereas CAR did not. Similarly, plasma aldosterone concentration and plasma renin activity overlapped, whereas ARR did not. These observations indicate that measurement of these endogenous variables (in one blood sample) allows the specific diagnoses of primary hypocortisolism and primary hypoaldosteronism.

Adrenal Insufficiency↗