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H J Karl

Publications and source records attributed to H J Karl.

At least 19 recordsLinked to original sources
PubMed1984

Urinary cholesterol: its association with a macromolecular protein-lipid complex.

The cholesterol-containing complexes in the urine of normal subjects and patients with diseases accompanied by hyperexcretion of urinary cholesterol were characterized. In normal subjects, the major portion of the recovered urinary cholesterol was eluted in the void volume fractions after gel chromatography on Bio-Gel A-5m; this suggested an association with a macromolecular complex above 5 X 10(6) daltons. A comparable elution pattern was seen in most of the urines of the patients with benign or malignant diseases of the kidneys or the urogenital tract. However, in single patients with hyperexcretion of urinary cholesterol, considerable amounts of cholesterol were detected in the included volume of the column. This was caused by additional excretion of high density lipoproteins or both high and low density lipoproteins in the urine which could be identified in these fractions by agarose electrophoresis and immunodiffusion. These results indicate that the macromolecular complex represents the majority of the recovered urinary cholesterol in normal subjects and in disease states with known hyperexcretion. Macroscopically, the isolated cholesterol-containing complex in the void volume fractions was turbid, and electron microscopy showed lipoprotein-like particles with diameters ranging from 300 to 700 A. The chemical analysis revealed median values of protein (46.0%), triglycerides (16.3%), cholesterol (8.2%), and phospholipids (29.5%) in normal subjects and comparable results in the patients with benign or malignant diseases of the kidney and the urogenital tract. Ethanolamine glycerophospholipids, phosphatidylcholine, sphingomyelin, and phosphatidylserine were the main phospholipid components. After ultracentrifugation in a CsCl gradient, the cholesterol-containing complex was found between densities 1.1 and 1.3 g/ml. By SDS polyacrylamide electrophoresis, up to 17 protein subunits in the molecular weight range of 14,000 to 87,500 were separated. Immunodiffusion studies showed in about 40% precipitin lines against anti-human albumin, but no reactions against anti-human apoHDL and anti-human apoLDL. However, immunodiffusion of the macromolecular complex against anti-liver-specific and anti-kidney-specific lipoproteins revealed single precipitin lines. In conclusion, the isolated cholesterol-containing urinary complex showed many characteristics of membrane-associated protein-lipid particles of the human kidney and even the liver. These proteolipids are the major source of urinary cholesterol in normal and disease states.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1983

Molecular heterogeneity of human chorionic gonadotropin and its subunits in testicular cancer.

The secretion of human chorionic gonadotropin and its subunits was examined by a heterologous hCG/hCG-beta radioimmunoassay and homologous radioimmunoassays of the alpha- and beta-subunit in patients with nonseminomatous testicular germ cell tumors. Of 53 patients, 32 (60%) had elevated levels of hCG (9 IU/l-4.5 million IU/l), 12 (23%) elevated serum concentrations of hCG-beta (20-286 micrograms/l) and 8 (15%) of hCG-alpha (14-498 micrograms/l). A selective elevation of hCG-subunits without the hormone was never observed. Serum concentrations of hCG-beta were to low to interfere in the heterologous radioimmunoassay using 125I-hCG and anti-hCG-beta antiserum. Gelfiltration of patient's sera (n = 5) on Ultrogel AcA 44 column confirmed the secretion of free subunits and additionally a high molecular form of hCG-beta (70,000) in three of five serum specimens. Furthermore, the molecular heterogeneity of hCG and hCG-subunits was examined by affinity chromatography on Concanavalin A (Con A)-sepharose. There was a significant difference of Con A nonreactive hCG and hCG-alpha between patients with testicular cancer (hCG:2-82%; mean, 22%; n = 7; hCG-alpha: 11-61%; mean, 31%; n = 7) and pregnant women (hCG: 0%; n = 3; hCG-alpha: 0-13%; mean, 6%; n = 5). Con A nonreactive and reactive hCG of patients with cancer revealed similar binding in a radioreceptor gonadotropin assay. The Con A nonreactive fraction of the beta-subunit was determined to be 20-73% (mean, 50%; n = 6) in serum samples of patients with testicular cancer and did not differ from the percentage in pregnant women (29-67%; mean, 46%; n = 4). The lectin binding heterogeneity of hCG and hCG-alpha indicate structural variations in the carbohydrate chains. It is assumed that Con A nonreactive hCG and hCG-alpha are directly liberated by nonsecretory mechanism from tumor cells into the circulation. Determination of hCG released by cell damage may have clinical significance in patients with testicular cancer under chemotherapy.

Choriocarcinoma↗
PubMed1983

Ketoconazole inhibits cortisol secretion of an adrenal adenoma in vivo and in vitro.

Ketoconazole (Nizoral), an oral broad spectrum antifungal agent, inhibits ergosterol synthesis in fungi and cholesterol synthesis in mammalian cells by inhibition of the 14-demethylation of lanosterol. After a blunted cortisol response to ACTH in normal men after ketoconazole has been shown by others we studied the influence of the antifungal agent on the cortisol secretion in a patient with a cortisol producing adrenal adenoma in vivo and in vitro. Repeated oral doses of ketoconazole (200 mg every 5 h over a period of 48 h) induced a reproducible clear-cut fall of serum cortisol levels under 2.5 micrograms/dl. The inhibitory effect of the cortisol secretion could be detected first 5 h after the first dose, 9 h after the last dose cortisol levels recovered. In addition the inhibitory effect of ketoconazole on cortisol secretion could be reproduced in vitro by incubating tissue slices of the excised adrenal tumor together with the antifungal agent in concentrations equivalent to therapeutic serum levels. These findings emphasize that patients with an autonomous cortisol production caused by an adrenal tumor are prone to dangerous hypoadrenalism if treated with ketoconazole.

Adenoma↗
PubMed1982

Results of oral TRH test in the differentiation of compensated and decompensated autonomous thyroid nodules.

In 17 patients with compensated autonomous adenomas of the thyroid, iv thyrotropin releasing hormone (TRH) tests (200 microgram) and oral TRH tests (40 mg) were performed. In nine of these patients, thyroid-stimulating hormone (TSH) 30 min after iv TRH showed a normal (greater than 2.7 microU/ml) and in eight patients a subnormal (less than 2.7 microU/ml) or negative response. However, after prolonged oral stimulation with 40 mg TRH, after 120-180 min TSH was normal (greater than 2.7 microU/ml) in 15 and subnormal (less than 2.7 microU/ml) in two patients. In 20 patients with decompensated autonomous thyroid nodules. TSH was not detectable (less than 0.8 microU/ml) after iv or oral TRH stimulation. Therefore, the oral TRH stimulation test seemed to be superior to the iv TRH test in the discrimination of compensated and decompensated autonomous adenomas of the thyroid.

Adenoma↗
PubMed1982

Urinary cholesterol in cancer screening.

Cholesterol determinations in morning urine samples were taken in 235 selected patients with a positive test for microscopic hematuria. Values ranged from 0.2 to 76.0 mg (median 5.5) in 23 patients with urologic malignancies and from 0.1 to 33.4 mg (median 1.1) in 38 patients with various benign diseases of the kidney or urogenital tract. In the 28 patients with urinary tract infections and 146 subjects without evidence of disorders of the kidney and the urogenital system, urinary cholesterol excretion was usually normal (0.1 to 1.9 mg; median 0.35). Using 1.0 mg urinary cholesterol per morning urine as a cutoff point, sensitivity for urologic carcinomas is about 80 per cent with a comparable high specificity of 90 per cent. Therefore, subsequent measurements of urinary cholesterol in populations with microscopic hematuria could define two groups, one with high prevalence and one with low prevalence of urologic malignancies. The less complicated colorimetric instead of gas-liquid chromatographic determination of urinary cholesterol can be recommended as a screening test for urologic carcinomas in populations with microscopic hematuria.

Aged↗
PubMed1981

Studies on the clinical significance of nonesterified and total cholesterol in urine.

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean +/- 2 SD) of 0.2-2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3-3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasizing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers.

Adolescent↗
PubMed1981

Is urinary cholesterol determination a possible screening test for urological carcinomas?

It has been suggested that the determination of urinary cholesterol may be of possible value in the diagnosis of urogenital carcinomas, especially of the prostate, kidney and bladder, but it has not proven whether this method could be used as a screening test in large numbers of patients. 430 males and 545 females over 50 years old were selected for the study. Total urinary cholesterol values exceeding the upper 3 SD limit of 5. 1 mg/24 h (regarded as positive results) were present in 13 males (3%) and 9 females (1.6%). Besides benign diseases of the kidney and the urogenital tract, 2 carcinomas of the bladder and 1 carcinoma of the kidney were detected in the male group with elevated urinary cholesterol excretion. In view of the expensive methodology and most importantly because of the low prevalence of urological carcinomas in unselected populations this method cannot be recommended as a primary screening test. This does not exclude the possibility that urinary total cholesterol determinations could be successfully applied in preselected populations with an increased prevalence of urological carcinomas.

Aged↗
PubMed1981

Urinary cholesterol in follow-up of patients with urologic carcinomas or benign prostatic hyperplasia.

Urinary cholesterol was determined in follow-up in 2 patients with prostatic adenoma, 3 patients with prostatic carcinoma, 3 patients with carcinoma of bladder, and 4 patients with carcinoma of kidney. All patients revealed marked urinary cholesterol hyperexcretion prior to surgery. Except for 1 patient with prostatic carcinoma, excretion of urinary cholesterol normalized at least six weeks after resection. In 1 remarkable case a localized recurrence of a transurethrally resected bladder tumor was associated with a marked increase of urinary cholesterol excretion six weeks prior to cystoscopy. The results point to a possible future value of this method in monitoring patients with bladder tumors, although additional studies are necessary.

Aged↗
PubMed1980

[Side-effects of corticosteroid therapy (author's transl)].

In reviewing the unwanted effects and side-effects of corticosteroid therapy, the principle guidelines for their use and contraindications are dealt with. Then the effects of a pharmacodynamic therapy on the metabolism of carbohydrates, proteins and fat and also the mineral balance are discussed and e.g. steroid diabetes, osteoporosis and myopathies are gone into. At the same time, the special properties of the various synthetic derivatives of cortisol, cortisone and corticosterone are referred to. Besides undesirable complications of corticosteroids in the gastrointestinal region, blood clotting and the influence on the course of infections and the psychic behavior, the side-effects on the skin and eyes are discussed. In closing, suggestions on the general measures of supervision and information of the patient are given. The principle of therapeutic decision is finally benefit: assessment of the risk to each patient.

Adrenal Cortex Hormones↗
PubMed1980

Determination of kallikrein by radioimmunoassay in human body fluids.

A sensitive and specific radioimmunoassay for human urinary kallikrein was developed, which allows tissue kallikrein determination in human urine, saliva, pancreatic juice, bile and sweat. In several body fluids a kallikrein-like antigen was found, but not in gastric juice and breast milk. According to gel filtration studies, complex formation of kallikrein with serum proteins or different molecular weight forms of kallikrein in serum and urine may be assumed. Pancreatic kallikrein secretion follows the same pattern after stimulation with secretin and cholecystokinin as trypsin and chymotrypsin in normal individuals. In chronic pancreatitis the kinetic behaviour remains unchanged with respect to the enzyme secretion, but the secretion of kallikrein is reduced to about 20%.

Body Fluids↗
PubMed1980

Radioimmunoassay of human urinary kallikrein: determination of human urinary kallikrein, II.

A radioimmunoassay for the determination of human urinary kallikrein was developed. The sensitivity of the assay was 0.5 microgram/l. Dose-response curves of human submandibular and parotid saliva, sweat, pancreatic juice and bile paralleled the standard curve obtained with purified human urinary kallikrein. Substances with similar antigenic determinants were also found in human serum, ascites, seminal plasma, amniotic fluid, cervical mucus, tears, liquor and faeces, but not in human breast milk and gastric juice. Moreover, immunoreactive material was detected in the urine of guinea pigs, orangoutangs and chimpanzees, but not in the urine of rats, cats and rabbits. Porcine acrosin and kallikrein, as well as bovine trypsin and chymotrypsin, showed no cross reactivity.

Cross Reactions↗
PubMed1980

Use of human chorionic gonadotropin and alpha-fetoprotein radioimmunoassays: specificity and apparent half-life determination after delivery and in patients with germ cell tumors.

The specificity of commercially available hCG and hCG-beta antibodies (anti-hCG-beta from N.I.A.M.D.D. (SB6), Serono (S), Biosigma (B), Union Carbide (UC) (I.R.E.) and anti-hCG from Union Carbide) were compared. Using 125I-hCG (CR 115), the crossreactivity with LH (LER 960) was 5.5% for SB6, 0.25% for S and 0.3% for B. In the homologous hCG system UC, crossreactivity was 0.06% with hCG-beta and 1.2% with LH, in the hCG-beta system UC, it was 2.2% with hCG and 0.01% with LH. Parallel standard curves for hCG, the 2nd I.R.P. hCG and hCG-beta were found exclusively with the 125I-hCG, anti-hCG-beta system S. Consequently accurate estimates of the total hCG or hCG-beta content in serum and standardization with the 2nd I.R.P. is possible. This system is the most useful for clinical purposes. The serum half-life of hCG was calculated in 10 pregnant women after delivery and was found to be 10 to 34 h. AFP half-life time, determined by the double antibody radioimmunoassay was 4.0 +/- 1.8 (+/- SD) days in pregnant women after delivery (n = 60) and 3.8 +/- 0.9 days in neonates during the first 16 days of life (n = 26). Altogether, apparent half-life determinations were carried out in 29 patients with nonseminomatous germ cell tumors. The results indicate that half-life determinations of hCG and AFP may have a predictive value with respect to the monitoring of therapy.

Antibody Specificity↗
PubMed1979

[Comparative examination of endocrine ophthalmopathy by means of ultrasonography, computerized tomography and fish bioassay].

In 35 patients with Graves' ophthalmopathy (GO) thyroid function was tested by T3-RIA, T4-RIA, TBI, TRH-test, thyroid scanning, and determination of thyroid autoantibodies. Additional ultrasonography (A-scan), computed tomography (CT) of the orbit, and the determination of an exophthalmogenic serum activity in fish bioassay was performed. Typical alterations for GO were observed in 26 cases with ultrasonography. CT showed an enlargement of medial and/or lateral rectus muscles in 24 of 33 patients, and in 17 cases a region of high density in the apex of the muscle cone. The density of retrobulbar fat after i.v. injection of contrast medium did not differ significantly from that observed in normal men. Characteristic signs of GO were not detected in only 2 cases using both methods together. Exophthalmogenic serum activity was found in the IgG fraction of serum protein. The incidence rate was high (69%), but for diagnostic purpose the fish bioassay cannot be recommended.

Adult↗
PubMed1979

[Clinical significance of cholesterol excretion in the urine].

Determination of urinary cholesterol has been suggested to be of possible value in the diagnosis of urogenital carcinomas especially of prostate, kidney and bladder. However, it has not been proven whether this method could be used as a screening test in large numbers of patients. 430 males and 545 females with an age above 50 years were selected for the study. Total urinary cholesterol values exceeding 5.1 mg/24 hours (regarded as positive results) were present in 13 males (3%) and 9 females (1.6%). In addition to benign diseases of the kidney and the urogenital tract, 2 carcinomas of the bladder and 1 carcinoma of the kidney were detected in the male group with elevated urinary cholesterol excretion. In view of the low prevalence of urological carcinomas and the cost of urinary cholesterol determination by GLC, this method cannot be recommended as a primary screening test, but could be of practical value in populations with microscopic haematuria and increased prevalence of urological carcinomas.

Cholesterol↗