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Biomedical subjects

D Klingmüller

Publications and source records attributed to D Klingmüller.

90 records · Page 5Linked to original sources
PubMed1985

Induction of puberty in a patient with hypogonadotropic hypogonadism: effect of sequentially applied hCG and pulsatile GnRH administration.

Pulsatile substitution with GnRH appears to be the therapy of choice in patients with Kallmann's syndrome, a well defined type of hypogonadotropic hypogonadism. We tried to simplify the treatment and to limit the subcutaneous GnRH therapy to the period absolutely necessary to induce spermatogenesis. Therefore we applied in sequence first hCG to stimulate testicular growth and second pulsatile GnRH application to induce spermatogenesis. We herein report that with this mode of therapy testicular growth from infantile to adult size and normal spermatogenesis could be achieved. We conclude that pulsatile GnRH application is a new effective therapy of hypogonadotropic hypogonadism which can be simplified considerably by pretreatment with hCG.

Adult↗
PubMed1985

Further characterization of the endogenous natriuretic and digoxin-like immunoreacting activities in human urine: effects of changes in sodium intake.

In the present study natriuretic activity and digoxin-like immunoreacting activity (DLIA) were determined in small molecular weight (MW) fractions of urine from healthy subjects during low (35 mmol/day) and high (greater than 400 mmol/day) sodium intake by bioassay and by a radioimmunoassay for digoxin, respectively. After gel filtration of urine on a Sephadex G-25 column the natriuretic activity appeared in the post-salt fraction SIV, whereas DLIA was present in small amounts in the salt fraction SIII and, with consistently higher activity, in the post-salt fraction SIV. Natriuretic activity significantly increased and DLIA decreased in fraction SIV with high sodium intake, but total urinary excretion of DLIA remained unaltered during changes in sodium intake. In addition, anion-exchange and reverse-phase chromatography revealed that DLIA is not specifically related to the natriuretic activity but also reflects unspecific binding of various urine constituents to this digoxin antibody. Although the antibody binds a natriuretic material, this radioimmunoassay is thus unsuitable to determine the endogenous natriuretic activity in urine fractions. Whereas they elute differently on reverse-phase chromatography, amino acid analyses revealed that both the natriuretic factor directly purified from the post-salt fraction SIV and the natriuretic material bound to the digoxin antibody have in common four amino acids at similar molar ratios. The physicochemical properties as evidenced by chromatographic and electrophoretic studies as well as enzymatic inactivation suggest that the low MW natriuretic factor(s) in human urine may be associated with a small peptide(s) of weak acidic nature.

Adult↗
PubMed1985

Digoxin-like immunoreacting substance(s) in the serum of patients with chronic uremia.

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.

Adult↗
PubMed1985

Maintenance of spermatogenesis by intranasal administration of gonadotropin-releasing hormone in patients with hypothalamic hypogonadism.

Pulsatile administration of GnRH is a new, effective therapy for idiopathic hypothalamic hypogonadism. This therapy requires a computerized pump to deliver GnRH intermittently or repetitive single injections each day. In order to simplify this mode of therapy, we first administered hCG to two of three patients to stimulate Leydig cells, and followed this by pulsatile sc administration of GnRH in all three patients. After induction of spermatogenesis, GnRH was administered intranasally, 200 micrograms every 2 h for 8 doses daily. In all patients treated, normal spermatogenesis was maintained by nasal administration of GnRH over a period of 90, 100, and 181 days, respectively. After this period the treatment was arbitrarily discontinued.

Administration, Intranasal↗
PubMed1985

Relation of endogenous digoxin-like immunoreacting activities to salt balance and renal function in man.

We have previously shown that a natriuretic factor which is present in a small molecular weight fraction (IV) of serum and urine from salt loaded animals and healthy subjects, respectively, inhibits the Na-K-ATPase enzyme in vitro and also binds to a specific digoxin antibody. In the present study digoxin-like immunoreacting activity (DLIA) was therefore determined in the serum of healthy volunteers during low (35 nmol/day) and high (greater than 400 mmol/day) sodium intake and of patients with chronic renal failure and serum creatinine concentrations ranging from 127 to 757 mumol/l. DLIA was determined with a radioimmunoassay for digoxin in native serum and in the salt (III) and post-salt (IV) serum fractions eluted from a Sephadex G-25 column. DLIA in native serum of healthy subjects was less than 0.125 ng/ml. After gel filtration DLIA eluted exclusively in the small molecular weight salt (F III) and post-salt (F IV) fractions. Whereas DLIA increased in F III and decreased in F IV, total DLIA in F III + IV slightly increased from 0.37 +/- 0.03 to 0.49 +/- 0.05 ng/ml (p less than 0.01) with the change from low to high sodium intake. DLIA in native serum of uremic patients ranged from 0 to 1.70 ng/ml and was detectable consistently only in patients with serum creatinine concentrations above 250 mumol/l. DLIA in F III which averaged 0.22 +/- 0.04 ng/ml and total activity which ranged from 0.11 to 0.88 ng/ml closely correlated with the degree of renal impairment (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[The primary structure of human free secretory component and the arrangement of disulfide bonds].

The amino-acid sequence and the arrangement of the disulfide bonds of the human free secretory component were completely elucidated by the methods of protein chemistry. The free secretory component is a monomeric glycoprotein (Mr approximately 86000), consisting of 558 amino acids with 7 carbohydrate chains bound to asparagine. The protein contains 20 cysteine residues but, as a special feature, no methionine. The polypeptide chain is divided into five regions of internal homology, 104 to 114 amino acids in length. The 20 cysteine residues form 10 disulfide bonds, 9 of which confirm the internal homology by their characteristic arrangement. The free secretory component also shows homology to immunoglobulins in some sections. A computer-supported tertiary structure is proposed for the free secretory component.

Amino Acid Sequence↗
PubMed1983

Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system.

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng . min-1 . kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p less than 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.

Animals↗
PubMed1983

Renal functional and metabolic studies on the role of preventive measures in experimental acute ischemic renal failure.

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.

Acute Kidney Injury↗
PubMed1982

Digoxin-like natriuretic activity in the urine of salt loaded healthy subjects.

In previous studies we have demonstrated a natriuretic factor of small molecular weight (less than 1,000 Daltons) in the serum and urine of salt loaded subjects. This factor isolated from salt loaded animals inhibits the Na-K-ATPase enzyme system. In addition, the natriuretic material isolated from plasma of salt-loaded dogs was shown to bind to specific digoxin antibodies. It was therefore suggested that a digitalis-like endogenous natriuretic factor (endoxin) is released in response to saline loading. In the present study we therefore investigated the presence of such an endogenous natriuretic digitalis-like activity in the urine of healthy volunteers during high salt intake. Using Sephadex G-25 for chromatographic separation of urine a material elutes as a single peak in the natriuretic post-salt fraction IV which is specifically bound to digoxin antiserum complex. Mean peak activity amounted to 1.55 +/- 0.48 ng/ml digoxin equivalents. We further purified the natriuretic material by immunoprecipitation with the digoxin antiserum complex. This purification procedure resulted in a more than 10-fold increase in specific natriuretic activity from 2.7 +/- 0.4 to 30.4 +/- 5.8 muEq Na+ x min-1 x mg-1. Thus the digitalis-like natriuretic activity previously observed in the plasma of saline loaded dogs is also present in the urine of healthy subjects during high dietary salt intake. Immunoprecipitation may offer a meaningful tool for further isolation and identification of the natriuretic hormone(s).

Adult↗
PubMed1982

[Suppressive treatment of normothyroid female goitre patients with reference to patient compliance (author's transl)].

Synthetic L-thyroxine (100-150 micrograms/d) was administered for 18 months to 110 female patients with normothyroid diffuse goitre size II. Reduction of size was observed in 60 patients after one year, in a further 10 there was no increase in size. Increase of neck circumference and thyroid gland size in 40 patients could be explained by patient non-compliance in 35 females. Renewed assessment of treatment results after another 6 months showed decrease of neck circumference and thyroid gland size in 98 out of the 110 patients. There were no significant differences among in vitro parameters (total thyroxine, normalisation of thyroxine ratio and triiodothyronine) assessed at 12 and 18 months among patients treated successfully and without success. However, the TRH test for delta TSH (TSH stim-TSH basal) showed significantly higher values after 12 months in the non-compliant group treated without success initially. These differences could not be demonstrated after 18 months. The results show that consideration of compliance behaviour in conjunction with the intravenous TRH test clearly improve results of conservative treatment of normothyroid diffuse goitre.

Adult↗
PubMed1981

Inner medullary osmolality and sodium concentration are decreased in rats during escape from DOCA-induced salt retention.

1. Papillary osmolality and sodium and potassium concentrations were determined in rats during a control period and during escape from the sodium-retaining effect of deoxycorticosterone acetate and compared with the changes observed after acute frusemide injection. 2. During escape, papillary osmolality [554 +/- 36 vs 754 +/- 42 mmol/kg of papillary water (H2O), P less than 0.005] and papillary sodium concentration (131 +/- 7 vs 182 +/- 8 mmol/kg H2O, P less than 0.001) were significantly decreased as compared with the control values, while papillary potassium concentration remained unchanged. 3. Frusemide decreased papillary osmolality to 538 +/- 41 mmol/kg H2O (P less than 0.005), papillary sodium concentration to 125 +/- 9 mmol/kg H2O (P less than 0.001) and papillary potassium concentration from 80 +/- 2 to 69 +/- 3 mmol/kg H2O (P less than 0.05). 4. The present results suggest that medullary portions of the distal tubule (probably the ascending loop of Henle) may represent one site of tubular sodium chloride rejection during escape from the sodium-retaining effect of deoxy-corticosterone acetate.

Animals↗
PubMed1979

[Purification and characterization of the free secretory piece of human colostrum (author's transl)].

The free secretory piece is isolated from human colostrum by gel filtration and ion-exchange chromatography in high yield (200 mg/l colostrum). DEAE-Cellulose chromatography separates the free secretory piece in two fractions which are electrophoretically distinct, but otherwise have the same characteristics, like molecular weight, antigenic determinants, N-terminal sequence, peptide map and amino acid composition. It was therefore concluded that the protein part of the secretory piece is homogenous.

Amino Acid Sequence↗
PubMedDate not supplied

Expression of CYP19 (aromatase) mRNA in different areas of the human brain.

The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM, aromatase) is an important step in the mechanism of androgen action in the brain. CYP19 expression has been demonstrated in the brain of various animal species and in the human temporal lobe. Studies on postnatal CYP19 expression in various other areas of the human brain are rare and carried out in a limited number of post mortem obtained tissue. Therefore, we investigated CYP19 mRNA expression in fresh human frontal and hippocampal tissues and compared them to the expression in temporal neocortex tissues. We studied biopsy materials removed at neurosurgery from 45 women and 54 men with epilepsy. Quantification of CYP19 mRNA was achieved by nested competitive reverse transcription-PCR. CYP19 mRNA concentrations were significantly higher in temporal (2.29+/-0.40 arbitrary units, AU, mean +/- SEM; n = 57) than in frontal neocortex specimens (0.92+/-0.17 AU; n = 18; P<0.04). In hippocampal tissue specimens CYP19 expression (1.41+/-0.18 AU; n = 24) was lower than in temporal neocortex specimens, but the difference did not reach statistical significance. Sex differences were not observed in any of the brain regions under investigation. In conclusion, CYP19 mRNA is expressed in the human temporal and frontal neocortex as well as in the hippocampus. Regardless of sex, CYP19 expression was significantly higher in the temporal than in the frontal neocortex.

Adult↗
PubMedDate not supplied

Treatment of idiopathic erectile dysfunction in men with the opiate antagonist naltrexone--a double-blind study.

Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone (LH) and testosterone, as well as sexual functions in animals and humans. We therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction aged 46.3 +/- 2.7 years (mean +/- SE, range 23.9-63.3) in a double-blind study with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of these men had persisted for 3.6 +/- 0.5 years despite libido maintenance; standard procedures had excluded any organic causes. Trial duration was 12 weeks overall. After a 4-week forerun, the patients received at first 25 mg naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50-mg dose of naltrexone/day or placebo. Each day the patients filled out a questionnaire detailing libido, degree of erection, frequency of sexual intercourse, and spontaneous morning erections. Serum concentrations of gonadotropins and testosterone were determined radioimmunologically in the initial stage and at the end of each phase. Both patient collectives had similar initial factors. The group treated with naltrexone showed a significant rise in spontaneous early morning erections during the treatment: from 2.8 +/- 0.3 to 4.2 +/- 0.3 a week (P < 0.001). The placebo group showed no significant change in spontaneous erections (2.4 +/- 0.3 and 2.6 +/- 0.3, respectively). The subjective parameters, however, such as libido, degree of erection, and frequency of sexual intercourse showed no significant difference within each group. There was no difference in LH, follicle-stimulating hormone, or testosterone concentrations in both groups. Thus, treatment with naltrexone significantly raises the rate of spontaneous early morning erections when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗