PubMed Health⌕ Search

Biomedical subjects

J H Robben

Publications and source records attributed to J H Robben.

18 recordsLinked to original sources
PubMed2006

Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus.

Intracellular retention of a functional vasopressin V2 receptor (V2R) is a major cause of congenital nephrogenic diabetes insipidus (NDI) and rescue of V2R mutants by nonpeptide antagonists may restore their basolateral membrane (BM) localization and function. However, the criteria for efficient functional rescue of G protein-coupled receptor (GPCR) mutants at clinically feasible antagonist concentrations are unknown. We found that the four nonpeptide antagonists SR49059, OPC31260, OPC41061, and SR121463B induced maturation and rescued the BM expression of eight of nine different V2R mutants, stably expressed in physiologically relevant polarized cells. The extent of maturation and rescued BM expression correlated with the antagonists' concentration and affinity for the V2R. Displacement of the antagonists by AVP and subsequent cAMP generation inversely correlated with the antagonists' affinities for the V2R but is partially influenced by antagonist-specific aspects. Despite limited increases in maturation and cell-surface expression of V2R mutants, the low-affinity SR49059 optimally induced functional rescue at high concentrations, due to its easy displacement by vasopressin. At clinically feasible antagonist concentrations, however, only the high-affinity antagonists OPC31260 and OPC41061 induced functional rescue, as at these concentrations the extent of BM expression became limited. In conclusion, functional rescue of mutant V2Rs at clinically feasible concentrations is most effective with high-affinity antagonists. As OPC31260 and OPC41061 are clinically safe, they are promising candidates to relieve NDI. Moreover, as numerous other diseases are caused by endoplasmic reticulum-retained GPCRs for which cell-permeable antagonists become available, our finding that high-affinity antagonists are superior is anticipated to be important for pharmacotherapy development of these diseases.

Animals↗
PubMed2005

Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism.

Because missense mutations in genetic diseases of membrane proteins often result in endoplasmic reticulum (ER) retention of functional proteins, drug-induced rescue of their cell surface expression and understanding the underlying mechanism are of clinical value. To study this, we tested chemical chaperones and sarco(endo)plasmic reticulum Ca2+ ATPase pump inhibitors on Madin-Darby canine kidney cells expressing nine ER-retained vasopressin type-2 receptor (V2R) mutants involved in nephrogenic diabetes insipidus. Of these nine, only V2R-V206D showed improved maturation and plasma membrane rescue with glycerol, dimethyl sulfoxide (DMSO), thapsigargin/curcumin, and ionomycin but not with other osmolytes or growth at 27 degrees C. This revealed that rescue is mutant specific and that this mutant is prone to rescue by multiple compounds. Rescue did not involve changed expression of molecular chaperones calnexin, heat-shock protein (HSP) 70, or HSP90. V2R antagonist SR121463B treatment revealed that V2R-V206D and V2R-S167T were rescued and matured to a greater extent, suggesting that the rescuing activity of a pharmacological versus chemical chaperone is broader and stronger. Calcium measurements showed that rescue of V2R-V206D by thapsigargin, curcumin, and ionomycin was because of increased cytosolic calcium level, rather than decreased endoplasmic reticulum calcium level. The molecular mechanism underlying rescue by DMSO, glycerol, and SR121463B is different, because with these compounds intracellular calcium levels were unaffected.

Animals↗
PubMed2005

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma.

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.

Animals↗
PubMed2005

Characterization of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus in a polarized cell model.

X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the gene encoding the vasopressin V2 receptor (V2R). For the development of a tailored therapy for NDI, knowledge of the cellular fate of V2R mutants is needed. It would be useful when this fate could be predicted from the location and type of mutation. To identify similarities and differences in localization, maturation, stability, and degradation of COOH-terminal GFP-tagged V2R mutants, we stably expressed nine mutants in polarized Madin-Darby canine kidney cells. The mutants V2R-L44P, -Delta62-64, -I130F, -S167T, -S167L, and -V206D were mainly expressed in the endoplasmic reticulum (ER) as immature proteins. These mutants had relatively short half-lives due to proteasomal degradation, except for V2R-Delta62-64. In contrast, V2R-R113W, -G201D, and -T204N were expressed in the ER and in the basolateral membrane as immature, high-mannose glycosylated, and mature complex-glycosylated proteins. The immature forms of V2R-R113W and -T204N, but not V2R-G201D, were rapidly degraded. The mature forms varied extensively in their stability and were degraded by only lysosomes (V2R-T204N and wild-type V2R) or lysosomes and proteasomes (V2R-G201D, -R113W). These data reveal that most missense V2R mutations lead to retention in the ER and suggest that mutations that likely distort a transmembrane domain or introduce a charged amino acid close to it make a V2R mutant more prone to ER retention. Because six of the mutants tested showed significant increases in intracellular cAMP levels on transient expression in COS cells, activation of these six receptors following rescue of cell-surface expression might provide a cure for NDI patients.

Amino Acid Sequence↗
PubMed2004

Regulation of the vasopressin V2 receptor by vasopressin in polarized renal collecting duct cells.

Binding of arginine-vasopressin (AVP) to its V2 receptor (V2R) in the basolateral membrane of principal cells induces Aquaporin-2-mediated water reabsorption in the kidney. To study the regulation of the V2R by dDAVP in a proper model, a polarized renal cell line stably-expressing V2R-GFP was generated. Labeled AVP-binding studies revealed an equal basolateral vs. apical membrane distribution for V2R-GFP and endogenous V2R. In these cells, GFP-V2R was expressed in its mature form and localized for 75% in the basolateral membrane and for 25% to late endosomes/lysosomes. dDAVP caused a dose- and time-dependent internalization of V2R-GFP, which was completed within 1 h with 100 nM dDAVP, was prevented by coincubation with a V2R antagonist, and which reduced its half-life from 11.5 to 2.8 h. Semiquantification of the V2R-GFP colocalization with E-cadherin (basolateral membrane), early endosomal antigen-1 (EEA-1) and lysosome-associated membrane protein-2 (LAMP-2) in time revealed that most dDAVP-bound V2R was internalized via early endosomes to late endosomes/lysosomes, where it was degraded. The dDAVP-internalized V2R did not recycle to the basolateral membrane. In conclusion, we established the itinerary of the V2R in a polarized cell model that likely resembles the in vivo V2R localization and regulation by AVP to a great extent.

Animals↗
PubMed2002

Locally produced growth hormone in canine insulinomas.

The production and release of GH has been demonstrated in a variety of extra-pituitary tissues. In this respect insulin-producing pancreatic tumours are also of interest because it has been observed that GH may promote islet cell proliferation. However, these effects have only been related to GH of pituitary origin and the possibility of local production of GH with autocrine-/paracrine effects has not been considered. In this study, a reverse transcriptase polymerase chain reaction (RT-PCR) was used to demonstrate the presence of GH mRNA in pancreatic tissue of five healthy dogs and insulinomas of 14 dogs. After Southern blotting of the RT-PCR products, blots were hybridized using a canine-specific GH-probe and quantified using phosphor imaging. GH gene expression was further demonstrated by in situ hybridization using a canine digoxigenin-labelled GH-specific cDNA probe. In addition, GH immunohistochemistry was performed. In five samples of normal pancreatic tissue a weak hybridization signal was found. This signal was significantly higher in nine of 12 primary tumours. In ten of 11 metastases there was a positive hybridization signal, and this signal was also significantly higher than in the primary tumours. In situ hybridization in one sample demonstrated that GH mRNA was only produced in the tumour cells. The local production of GH was confirmed by positive staining of tumour tissue with anti-GH antibodies in ten of 12 samples. It is concluded that canine insulinomas express the gene encoding GH mRNA. The locally produced GH may have an autocrine/paracrine effect on tumour progression. The relatively high expression levels in metastases of these tumours may be related to the low inhibitory influence of somatostatin outside the pancreas.

Animals↗
PubMed2000

Pyothorax in nine dogs.

The results of treatment of pyothorax using systemic antibiotics, drainage, and lavage of the pleural space, are reported for 9 dogs. All 9 dogs recovered completely. In 8 of the 9 dogs the follow-up period was at least 6 months and in none was there a relapse. The results obtained with this treatment are excellent in comparison with the results that have been reported for treatment with systemic antibiotics and drainage of the pleural space but without lavage. Apart from the addition of pleural lavage to the treatment protocol, the better result might be because migrating plant related foreign bodies did not seem to play an important role in the pathogenesis of pyothorax in this group of dogs.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1999

[Enteral, nutritional support for critically ill patients].

Critically ill patients are characterized by acute changes in their metabolism, which are described by the term 'hypermetabolism'. In combination with anorexia, hypermetabolism leads to a negative energy and nitrogen balance. Consequently, wound healing can be inhibited, resistance is reduced, and (multiple) organ failure can occur. With the aid of nutritional support these consequences can be counteracted. During hypermetabolism protein breakdown is increased, and it is necessary to supply extra protein in the diet of critically ill patients. The amino acid glutamine is an important source of energy for enterocytes, and extra glutamine can improve the protective function of the intestinal mucosa. Branched amino acids serve as energy source during the acute phase. Arginine can reduce symptoms of encephalopathy by improving the conversion of ammonia to urea. Extra arginine in the diet also improves resistance. Because of the increased energy demand, diets for critically ill patients should be rich in fat. Moreover, extra n-3 fatty acids can improve immune function. A diet supplemented with extra zinc seems warranted because of its beneficial effect on wound healing and its inhibitory effect on protein breakdown. The enteral route is preferred because it protects the mucosal barrier of the gut, and it is less expensive and easier than the parenteral route. An enteral diet for critically ill patients is presented. Various factors that determine the choice of technique for enteral feeding are discussed.

Animals↗
PubMed1999

[Pyothorax in nine dogs].

Nine dogs with pyothorax were treated with systemic antibiotics, and drainage and lavage of the pleural space. All nine dogs recovered completely. Eight dogs were followed up for 6 months or longer and none showed signs of relapse. The results of this treatment are excellent compared with those for treatment with systemic antibiotics and drainage of the pleural space but without lavage. Apart from the addition of pleural lavage to the treatment protocol, this difference in efficacy may be due to the fact that migrating grass seed awns do not seem to play an important role in the pathogenesis of pyothorax in dogs in the Netherlands.

Animals↗
PubMed1998

Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning.

The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted.

Animals↗
PubMed1997

[Anticoagulant rodenticide poisoning in dogs in The Netherlands].

The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide poisoning in dogs in the Netherlands was evaluated by a survey among Dutch veterinarians carried out by the National Poisons Control Center (NPCC). The survey included information on 54 dogs, 32 being treated by veterinarians who consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n = 19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31 dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2 died shortly after admission to the UUCCA. Signs of bleeding occurred especially in poisoning by brodifacoum (n = 16). In all but one of the dogs without hemorrhages, the intake of poison had taken place within 24 hours before presentation. The method of treatment varied, with the induction of vomiting and the use of vitamin K mentioned most. The choice of therapy was determined by the length of time after intake of the poison, the clinical signs and whether or not an anticoagulant toxicosis was suspected at the time of the initial examination. These findings provide the basis for discussion of several aspects of diagnosis and treatment.

Animals↗
PubMed1997

[Percutaneous placement of an esophagostomy tube in cats: first experience with a new technique].

A new technique for percutaneous placement of tube esophagostomy for enteral feeding in cats is described. The technique is characterized by its symplicity and rapid placement of the feeding tube. Its use is demonstrated in 8 cats in which nutritional support with enteral feeding was indicated. Placement of the tube was performed without complications. The feeding tube was tolerated well. Complications after placement were restricted to occasional vomiting after feeding (n = 2) and minor inflammation of the esophagostomy incission. Tubes could be removed after 7 to 16 (median 14) days. Two cats died as a result of the primary disease. This technique is a useful aid in the application of enteral feeding because of its simplicity and minimal complications.

Animals↗
PubMed1997

In vitro and in vivo detection of functional somatostatin receptors in canine insulinomas.

UNLABELLED: Ten dogs with hypoglycemia due to insulinomas were studied to assess the expression of somatostatin receptors (SSTRs) in canine insulinomas and its potential diagnostic value. METHODS: The response of circulating glucose and insulin concentrations to the subcutaneous administration of a somatostatin analog, octreotide, was measured. SSTRs were visualized in vitro by autoradiography. [Iodine-125-Tyr3]-octreotide and [125I-Tyr11]-somatostatin-14 (SRIF-14) were used as radioligands. SPECT was performed 6 hr after the injection of [111In-DTPA-D-Phe1]-octreotide. RESULTS: After subcutaneous injection of 50 micrograms octreotide, plasma glucose concentration rose from 2.3 +/- 0.2 mmol/liter to 3.2 +/- 0.3 mmol/liter at 3.5 hr (p < 0.05) and plasma insulin concentration decreased from 451 +/- 135 pmol/liter to a nadir of 249 +/- 115 pmol/liter at 30 min (p < 0.05). In vitro autoradiography revealed that all primary insulinomas and their metastases had specific SSTRs for both [125I-Tyr3]-octreotide and [126I-Tyr11]-SRIF-14. Scatchard analysis of SSTR binding in the tumor tissue of one dog revealed high-affinity binding sites for [125I-Tyr3]-octreotide (dissociation constant (Kd) 1.7 nM, maximum binding capacity (Bmax) 499 fmol/mg membrane protein). The primary tumor and/or metastases in five of six dogs could be visualized and localized by SPECT with [111In-DTPA-D-Phe1]-octreotide. In the remaining dog, multiple metastases (< 3 mm) were found in the liver at necropsy, apparently too small to be visualized by SPECT. CONCLUSION: The in vitro autoradiography and ligand binding studies indicate that canine insulinomas express one type of SSTR. This is in contrast with findings in humans where, on the basis of ligand binding studies, different subtypes of SSTRs have been identified. The uniformity of SSTRs, their high frequency of expression and the high incidence of metastatic disease make canine insulinomas very suitable for investigation of the value of SRIF analogs in the diagnosis and treatment of metastasized endocrine pancreatic tumors.

Animals↗
PubMed1995

Continuous monitoring of ECG in horses at rest and during exercise.

A method for the continuous monitoring of the electrocardiogram (ECG) of horses at rest and during exercise was evaluated in five healthy horses. The horses spent 24 hours in a loose box and performed a standardised exercise test on a treadmill during this period. Two bipolar leads were recorded, lead 1 between the xiphoid and the left withers, and lead 2 between the left ventral thorax and the left dorsal thorax, using disposable electrodes. The quality of the ECGs enabled both an 'operator-controlled' and an automatic analysis to be made. Lead 1 was the most stable during exercise and lead 2 during rest in the loose box. The heart rate and occurrence of arrhythmias were assessed over 22 hours. During the boxed period the heart rate varied from 31 +/- 2 to 138 +/- 11 beats per minute (bpm) and during exercise it varied from 79 +/- 8 to 177 +/- 12 bpm. All the horses had sinus arrhythmias, sinus tachycardias and second degree atrioventricular blocks. One horse developed a ventricular escape rhythm.

Animals↗
PubMed1989

[A comparison of parrot food commercially available in The Netherlands].

The composition of a number of parrot foods commercially available in the Netherlands was put to the test for the (partly hypothetical) needs of the larger psittacine birds such as African Grey parrots, Amazon parrots, macaws and cockatoos. These studies showed that the majority of the foods is multideficient. When the deficient foods are supplied to parrots without any additions, this will give rise to the appearance of disease. However, some of the products recently put on the market (Bogena and Kasper Fauna Food) comply better with the requirements of a 'complete parrot food'. As regards public enlightenment, food producers, petshops, consumer organisations and veterinarians are obviously responsible.

Animal Feed↗