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Biomedical subjects

J Hensen

Publications and source records attributed to J Hensen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Value of direct measurement of active renin concentrations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

UNLABELLED: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, measurement of plasma renin activity (PRA) has been the method of choice in diagnosing salt loss and in monitoring adequacy of mineralocorticoid replacement therapy. Due to methodological problems in PRA determinations, direct immunoradiometric assays for the measurement of active renin concentration have been developed. We measured PRA and active renin concentrations simultaneously in 39 patients with CAH (30 salt-wasting, 9 simple virilizing) to evaluate the potential role of this new method in the management of this disease. PRA was determined with an enzymatic assay (sample volume: 2 x 1000 microliters plasma), active renin concentration with a direct immunoradiometric assay (sample volume: 2 x 200 microliters plasma or serum). We found a highly significant correlation between active renin and PRA in our patients (P < 0.001), as previously shown in healthy subjects. Active renin was as reliable as PRA to assess the quality of mineralocorticoid replacement. CONCLUSION: In children, active renin determination is preferable to PRA determination because of methodological advantages and a smaller sample volume. It correlates well with PRA and determines the activation of the renin-angiotensin system as precisely as PRA. Active renin determination is useful in the surveillance of mineralocorticoid replacement therapy in CAH.

Adolescent↗
PubMed1996

Lithium induced polyuria and renal vasopressin receptor density.

BACKGROUND: Lithium, a drug frequently used for treatment of affective disorders, is known to cause a vasopressin-resistant state, leading to polyuria and polydipsia. It has been suggested that lithium interacts with the renal V2-vasopressin receptor. Detailed studies on the influence of lithium on the AVP receptor, however, have so far been difficult due to the lack of a suitable radioligand with high specific activity and high affinity. METHODS: Using 125I-[8-(p-(OH)-phenylpropionyl)]- LVP, we studied the effects of lithium on V2-vasopressin receptors in male Sprague-Dawley rats and LLC-PK1 cells. Rats, having free access to water, were orally treated with 10 mg lithium/100 mg b.w./day or placebo for 10 days. Scatchard analysis was performed using membranes prepared from homogenized renal papillae. RESULTS: Lithium caused significant polyuria and an impaired renal concentration capacity after water deprivation. Binding studies showed no effect of lithium on binding affinity KD (0.98 +/- 0.21 nmol/l vs. 0.86 +/- 0.15 nmol/l (Li) (n.s.). Receptor density, however, significantly decreased from 130 +/- 12.3 nmol/kg protein in controls (n = 8) to 101.7 +/- 13.4 nmol/kg protein (n = 8), (P < 0.05). Plasma osmotically and AVP were not significantly altered by lithium treatment. Vasopressin receptor density on LLC-PK1-cells, a pig renal cell line, was not changed by preincubation with lithium (312 +/- 22 nmol/kg vs. 329 +/- 25 nmol/kg (Li) (n = 6, n.s.). CONCLUSIONS: The decrease of AVP-receptor density in vivo might be related to vasopressin resistance, either primary, or secondary to other factors, e.g. actual water transport.

Animals↗
PubMed1996

[Hormonally inactive hypophyseal adenomas: the results and late sequelae after surgery and radiotherapy].

PURPOSE: External radiation therapy for non functioning pituitary adenomas is clearly indicated in inoperable patients, after incomplete transsphenoidal microsurgery and in case of tumor progression. This retrospective analysis gives results and toxicity following surgery and postoperative radiotherapy of non-functioning pituitary adenomas. PATIENTS AND METHODS: Between 1983 and 1990, 50 patients with non-functioning pituitary adenomas received combined treatment at our institutions. Surgical approaches were transsphenoidal (61%), transcranial (24%) or a combination of both (15%) in short intervals. All 50 patients received a full-dose radiotherapy with single fractions between 1.9 and 2.1 Gy (median 1.9 Gy) and total doses between 46 and 63 Gy (median 48 Gy). Field sizes ranged between 20 and 72 cm2 (median 30 cm2). Endpoints of this study were: progression-free survival, late effects of brain, optic nerve and intracranial vessels, visual impairment and hypothalamic-pituitary dysfunction. Median follow-up was 54 months. RESULTS: Forty-seven of the 50 patients remained progression-free. Patients over age 60 years progressed more frequently (3/17) as compared to younger patients (0/33, p = 0.034). Following radiotherapy vision improved in 8 patients (16%), 14 patients (28%) experienced a visual impairment between 10% and 60% (according to the grading system of the German Ophthalmologic Society). In multivariate analysis no influence of age (p = 0.097) or biologically effective dose (BED) (p = 0.11) was seen on visual impairment. Three patients (6%) experienced late effects with optic neuropathy in 2 cases and temporal lobe necrosis in 1 case. Only the BED had a significant impact on late effects (p = 0.0094). Adrenal, thyroid and gonadal function abnormalities were present in 58%, 66% and 96% of the patients at last follow-up, respectively. CONCLUSIONS: Radiotherapy after incomplete transsphenoidal or transcranial surgery of non-functioning pituitary adenoma is an effective treatment. Future perspectives must include the better defining of high-risk patients and the reduction of late morbidity.

Adenoma↗
PubMed1995

Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors.

Chlorpropamide (CP), a sulfonylurea used for treatment of non-insulin dependent diabetes mellitus, is known to potentiate the antidiuretic action of arginine vasopressin (AVP), predisposing to hyponatremia. It has been suggested that CP acts directly on the antidiuretic vasopressin receptor. Detailed studies on the influence of CP on the AVP receptor, however, have been hampered by lack of a suitable radioligand. Using a newly developed radioiodinated derivative of AVP with high specific activity and high affinity for the AVP V2-receptor (125I-[8-(p-(OH)-phenylpropionyl)]-LVP), we studied the role of AVP V2-receptors in CP-induced water retention. Male-Sprague-Dawley rats were treated orally with 40 mg CP/day or placebo for 7 days, after which Scatchard analysis was performed using membranes prepared from homogenized renal papilla. After oral water load, CP-treated rats but not control rats showed a significant decrease in plasma osmolality (289 +/- 2.2 to 284 +/- 0.8 mosmol/kg, p < 0.05). The Kd was 0.69 +/- 0.16 nmol/l in controls and 0.70 +/- 0.12 nmol/l after CP treatment (NS); Bmax was 129 +/- 5.3 nmol/kg protein in controls (N = 8). Chlorpropamide significantly increased receptor density (Bmax) to 167 +/- 8.4 nmol/kg protein (N = 8) (p < 0.05). Plasma AVP did not change significantly during CP treatment. These data show for the first time that CP in vivo increases the density of AVP V2 receptors without altering plasma AVP. This is associated with an impairment in water excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Somatostatin receptor expression in the thyroid demonstrated with 111In-octreotide scintigraphy.

Neuroendocrine tumors with somatostatin receptor expression may be localized by 111In-octreotide scintigraphy. This study examines those thyroid conditions where 111In-octreotide uptake could be observed also in the thyroid gland. 26 consecutive patients who underwent 111In-octreotide scintigraphy for tumor localization were additionally examined for thyroid disease by sonography and 99mTc-pertechnetate scintigraphy. 12 of these patients had no significant thyroid uptake and had an euthyroid normal-sized thyroid gland 14 patients with 111In thyroid uptakes had endemic goiters, two of them with thyroid autonomy and one with Graves' disease. Thus, 111In-octreotide thyroid uptake was predominantly seen in patients with endemic goiter with or without thyroid autonomy.

Adult↗
PubMed1994

[Calcitriol administration during pregnancy in a partial DiGeorge anomaly].

A 23-year-old pregnant woman was known since birth to have partial DiGeorge syndrome with idiopathic hypoparathyroidism and clinically suspected thymus hypoplasia. The hypocalcaemia had until recently been treated with 1000 IU vitamin D3 daily. During the 9th week of pregnancy the serum calcium level was 1.9 mmol/l, the phosphate one 1.58 mmol/l and parathormone 5.6 pg/ml. To ensure better control, calcitriol was given (1.25-[OH]2-vitamin D3, initially 1 microgram daily and then, from the 22nd week of pregnancy onward, 1.5 micrograms daily), as well as calcium gluconate and lactate (initially 300 mg daily, then 900 mg daily). The serum calcium level at that time was between 2.0 and 2.5 mmol/l. Because of toxaemia of pregnancy the patient was hospitalized and confined to bed during the 37th week, whereupon the serum calcium level rose from 2.2 to 2.7 mmol/l, but a decrease in calcitriol dosage resulted in a decrease to within normal limits within one day. A girl was delivered by section in the 39th week: she had normal serum calcium and phosphate levels and appeared healthy.

Adult↗
PubMed1994

[Thyrotropin-producing hypophyseal adenoma in a case with congenital thyroid gland hypoplasia].

A 56 year old mentally disabled woman of short stature was admitted to our hospital because of severe chest pain and dyspnoea. An extended myocardial infarction in the anterior wall was clinically found and confirmed by autopsy. On admission cretinism with massive myxedema was diagnosed, which was confirmed by subsequent laboratory findings. Only at the base of the tongue thyroid tissue 3 mm in diameter was found. In the anterior lobe of the pituitary gland areas with nodular hyperplasia and microadenomas of TSH-producing cells were detected. Thyrotroph adenomas in long standing hypothyroidism are rare. There are only few reports on congenital hypothyroidism as primary underlying disease.

Adenoma↗
PubMed1994

Effect of bacitracin on the degradation of a vasopressin receptor ligand with high affinity for the V1 and V2 vasopressin isoreceptors.

We previously described a new iodinated vasopressin analogue (N epsilon-[125I]L-Tyr-[Lys8]-vasopressin) with high affinity for the vasopressin V1 and V2 isoreceptors. The aim of the present study was: i) to analyse the degradation pathway of N epsilon-[125I]L-Tyr-[Lys8]-vasopressin and (ii) to look for an effective inhibitor of radioligand degradation. N epsilon-[125I]L-Tyr-[Lys8]-vasopressin was processed in a temperature-dependent manner by crude cell membranes from LLC-PK1 cells. Only one degradation product was seen using RP-HPLC. The degradation product co-eluted with monoiodotyrosine. The stereoisomer, N epsilon-[125I]D-Tyr-[Lys8]-vasopressin, underwent the same degradation process. Bacitracin prevented degradation at doses as low as 40 mg/l without alterating the binding affinity.

Animals↗
PubMed1993

The functional spectrum of adrenocortical adenomas.

Adrenocortical adenomas (ACA) are frequently discovered at autopsy. Nowadays, modern radiologic techniques incidentally uncover the usually silent ACA during lifetime. On the basis of various reports and the results of endocrine tests, i.e. dexamethasone suppression (DST) and CRH response, we characterize 3 major types of functioning ACA. Type I ACA (cortisol < 100 nmol/l after 1 mg dexamethasone (DXM)) comprises the majority of the so-called 'nonfunctioning' adrenocortical adenomas. However, these adenomas may not be 'truly nonfunctioning' ACA, as their mean FMAX/ACTHMAX-ratio after CRH is significantly higher than in controls without ACA. Also, 19-iodocholesterol adrenal scan has shown persistent adrenal uptake despite DXM administration in some patients with normal DST. Type II ACA ('pre-Cushing's') is comparable to the euthyroid autonomous adenoma. The results of function tests suggest the existence of an ACTH-hyperresponsive subtype. Finally, type III ACA are associated with overt hypercortisolism. An ACTH-responsive and an ACTH-unresponsive form can be characterized. A continuous functional spectrum and the transition between the different types of adenomas is discussed.

Adenoma↗
PubMed1993

Influence of sodium and potassium diets on adrenal vasopressin content and direct effects of vasopressin on aldosterone synthesis in adrenocortical cells.

Two questions were investigated to elucidate the adrenal function of arginine vasopressin (AVP) in controlling aldosterone secretion: Are vasopressin tissue concentrations in the adrenal modulated by diets that influence aldosterone secretion? Does its direct stimulation of aldosterone secretion from adrenal cells in vitro suggest that vasopressin plays an important role in controlling aldosterone? Diets that modulate aldosterone secretion from rat adrenals did not modulate concentrations of AVP in this tissue: Adrenal AVP concentrations did not differ significantly between rats on low- and high-sodium (22.9 +/- 3.8 and 32.4 +/- 6.4 pg/g) or between low- and high-potassium (25.6 +/- 2.5 and 12.5 +/- 7.3 pg/g) diets. Although the existence of AVP receptors on adrenocortical cells incubated in vitro and the stability of AVP during cell incubation was confirmed, AVP had only a minor direct effect on steroid secretion in short-term incubations alone and in combination with angiotensin II (A II), potassium and atrial natriuretic factor (ANF). The importance of AVP for an indirect control of aldosterone secretion in vivo is discussed.

Adrenal Cortex↗
PubMed1993

Expression of vasopressin receptors (V2-subtype) on LLC-PK1 cells during cell culture.

Vasopressin receptor expression on LLC-PK1-cells (a porcine renal tubular cell line) during cell culture is still not fully understood. We studied receptor expression using a novel vasopressin analogue with high specific radioactivity ([125I][8-p-hydroxy-phenylpropionyl]-lys8-vasopressin, 74EBq/mol (2000 Ci/mmol)). LLC-PK1 cells were grown in monolayers for 1 to 6 days. Scatchard analysis performed with membranes of LLC-PK1 cells revealed a single binding site with a binding constant (Kd) of 0.46 +/- 0.04 nmol/l. During cell culture, the binding constant (Kd) was not altered, but receptor density increased significantly (21,115 +/- 645 receptors per cell, day 2; 42,315 +/- 1512 receptors per cell, day 6). A receptor occupancy of about 30% was found to be associated with a cAMP stimulation of 50%. The receptor reserve might be even higher because, by using a highly specific oxytocin antagonist, we found that 20% of the occupied [125I][8-p-hydroxy-phenylpropionyl]-lys8-vasopressin-binding sites are oxytocin receptors. For lys8-vasopressin receptor studies, great care has to be taken to examine cells in identical culture phases.

Animals↗
PubMed1992

High specific activity 125I- and 35S-labeled vasopressin analogues with high affinity for the V1 and V2 vasopressin isoreceptors.

Since iodination of the tyrosine residue in the pressin ring of vasopressins abolishes binding to the V2 (renal) isoreceptor, the low specific activity tritiated vasopressins have been the only radioligands available for this receptor. Alternative vasopressin radioligands are described in the present study. N-tert-Butoxycarbonyl- (N-t-Boc) 125I-tyrosine or [35S]methionine were conjugated to the 8th amino acid of lysine- (LVP) or deamino-ornithine-vasopressin via active succinimidyl esters. Following the purification on C-18 reverse-phase high pressure liquid chromatography, t-Boc removal, and a second high pressure liquid chromatography purification, specific activities of 2200 and 1300 Ci/mmol were obtained for the 125I- and the 35S-labeled ligands, respectively. These vasopressin analogues, conjugated outside the pressin ring, were found to bind with high affinity to the V1A (vascular) and V2 vasopressin isoreceptors (Kd less than or equal to 10(-9) M) and to retain the full biological activity of intact vasopressin. The present study demonstrates the possibility of producing high specific activity radioligands with high affinity for the V1A and V2 vasopressin isoreceptors by conjugating labeled moieties to the 8th amino acid of vasopressin analogues. Since these new radioligands have specific activities much higher than the tritiated ligands (1300-2200 versus 10-30 Ci/mmol), they should provide considerable advantages in the future study of the physiology and biochemistry of the AVP receptors.

Adenylyl Cyclases↗
PubMed1992

Internalization of V2-vasopressin receptors in LLC-PK1-cells: evidence for receptor-mediated endocytosis.

The mechanism of internalization of the vasopressin-receptor (V2-subtype) of LLC-PK1-cells, a pig renal tubular cell line, is unknown. We studied internalization utilizing a novel, highly specific vasopressin analogue ((125I)-[8-p(OH)-phenylpropionyl]-LVP, 2000 Ci/mmol). Scatchard analysis performed with membranes of LLC-PK1-cells revealed a Kd of 0.8 +/- 0.2 nM and a Bmax of 366 +/- 41 fmol/mg of protein. Degradation of the ligand was excluded by RP-HPLC-analysis. Internalization was proven by the acid-wash technique, quantitative light-microscopic autoradiography and electron microscopy. The ligand was internalized in a time- and temperature-dependent manner. At 4 degrees C, no uptake was found; at 22 degrees C, after 30 min of incubation, more than 50% of the radioligand was found inside the cell. Electron microscopy demonstrated that plasma-membrane bound vasopressin receptors are internalized by receptor-mediated endocytosis via coated pits.

Animals↗
PubMed1992

Intracellular distribution of endothelin-1 receptors in rat liver cells.

We studied the binding of (125I)-endothelin-1 as well as that of the vasopressin analogue (125I)-[8-phenylpropionyl]-LVP to purified plasma membranes, Golgi cisternae and cell nuclei from rat liver. Cell organelles were isolated by differential centrifugation and discontinuous sucrose gradients. Endothelin-1 exhibited specific binding to plasma membranes, Golgi cisternae and nuclei, while the binding of (125I)-[8-phenylpropionyl]-LVP was restricted to the plasma membranes. The number of receptors (Bmax) and the binding constants (Kd) were determined by Scatchard analysis of competition binding studies. In all cases only one class of Et-1 binding sites could be detected. The presence of Et-1 receptors on the Golgi complex either indicates that the receptor is glycosylated within the cisternae or alternatively, there exists a recycling pathway. The unexpected finding of Et-1 receptors on highly purified nuclei suggests that this peptide may exert part of its biological functions intracellularly via the nucleus.

Animals↗
PubMed1992

Atrial natriuretic peptide kinetic studies in patients with cardiac dysfunction.

Three studies were performed: (1) a controlled investigation of alpha-human atrial natriuretic peptide (alpha-hANP) total body production and metabolic clearance rates using a bolus infusion technique (controls, patients 1 to 6); (2) a study of alpha-hANP kinetics in cardiac dysfunction patients using a constant infusion method (patients 7 to 14); and (3) a right heart catheterization study to determine the amount of alpha-hANP released into the circulation at the level of the right heart, estimated by the step-up in alpha-hANP concentration between the superior and inferior vena cava and the pulmonary artery, in the patients with left ventricular dysfunction. Baseline venous plasma alpha-hANP was 27.3 +/- 16.5 pg/ml in the controls (mean +/- SD; N = 6), 141.6 +/- 138.0 pg/ml in patients 1 to 6 (P less than 0.05 compared to controls), and 167.5 +/- 145.7 pg/ml in patients 7 to 14. Total body alpha-hANP production rate was markedly elevated in patients 1 to 6 compared to controls (0.45 +/- 0.36 vs. 0.11 +/- 0.06 micrograms/min, P less than 0.05) and was similar to that determined by the continuous infusion technique in patients 7 to 14 (0.62 +/- 0.44 micrograms/min, P = 0.49 compared to patients 1 to 6). alpha-hANP release into the right heart (0.17 +/- 0.11 micrograms/min), however, was significantly lower than total body production rate in the cardiac dysfunction patients, indicating that total body alpha-hANP secretion occurs from sites in addition to drainage into the right heart via the coronary sinus and anterior cardiac veins. Right atrial pressure correlated with the alpha-hANP released into the right heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Atrial natriuretic peptide and urinary cyclic guanosine monophosphate in patients with chronic heart failure.

Circulating concentrations of human atrial natriuretic peptide (hANP) are elevated in patients with heart failure; however, the natriuretic effect of hANP is blunted in these patients. In this study, the relationship between urinary cGMP, the second messenger for the natriuretic effect of hANP in vivo, and endogenous hANP was examined in six patients with heart failure and four normal subjects. In addition, right heart catheterization for the determination of central hemodynamics was performed in the heart failure patients. The heart failure patients were in New York Heart Association Classes II to IV and were receiving no medications at the time of the study. Supine plasma hANP and urinary cGMP concentrations were determined on two occasions in each subject, as were right and left atrial pressures in the heart failure patients. At the time of study, the patients were in positive sodium balance, and control subjects were in normal sodium balance. Plasma hANP and urinary cGMP excretion rates were elevated in heart failure patients as compared with those in controls: hANP, 139.0 +/- 42.0 versus 22.0 +/- 6.1 pg/mL (P less than 0.05); urinary cGMP, 1.14 +/- 0.31 versus 0.35 +/- 0.05 nmol/min (P less than 0.05). In heart failure patients, right atrial pressure correlated positively with plasma hANP (r = 0.96; P less than 0.01) and urinary cGMP concentrations (r = 0.93; P less than 0.05) and the excretion rate (r = 0.92; P less than 0.05). Moreover, plasma hANP was strongly correlated with urinary cGMP concentration (r = 0.91; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗