Search PubMed⌕ Search

Biomedical subjects

S Werner

Publications and source records attributed to S Werner.

At least 289 records · Page 16Linked to original sources

Normal growth hormone secretion is rare after microsurgical normalization of growth hormone levels in acromegaly.

The effect of microsurgery on growth hormone (GH) secretion was studied in 34 patients with acromegaly. All patients showed enlarged sella volumes according to encephalography and macroadenomas at surgery. Preoperative GH levels were elevated in all 34 patients and 14 had concomitant hyperprolactinemia. There was a correlation between basal GH levels and sella size. Visual field defects, suprasellar extension, long duration of the disease, hyperprolactinemia and aneuploidy were noted in patients with low as well as high levels of GH preoperatively. The average reduction of GH levels in the total series was 71 +/- 21% (mean +/- SD). A notably similar reduction of GH levels was seen regardless of preoperative GH levels, concomitant hyperprolactinemia, visual field defects, size of the adenoma, invasive growth or increasing experience of the surgeon. Therefore, normal GH levels after surgery were reached mainly in patients with moderate GH increments preoperatively. GH levels were normalized by surgery in 15 patients but only four of these showed normal GH response to TRH and iota-dopa tests. Thus, only four patients (12%) fulfilled these criteria for cure of GH homeostasis.

Acromegaly↗

Melatonin and corticosteroid response to metyrapone in patients with pituitary disease.

Melatonin secretion is dependent both on the environmental lighting and noradrenergic control and seems to be related to the ACTH-cortisol secretion. The aim of the present study was to further elucidate the relationship between ACTH-cortisol and melatonin. For this purpose we chose the Metyrapone test. The melatonin secretion was studied in 10 patients, and increased significantly in 8/10 during and in one after the Metyrapone administration. These results further support a relationship between melatonin and ACTH-cortisol secretion, possibly through a suprapituitary interaction.

Adrenal Cortex Hormones↗

Variations of cationic proteins from eosinophil leukocytes in food intolerance and allergic rhinitis.

Challenge tests were performed in patients with food intolerance and allergic rhinitis to evaluate the usefulness of measurement of the eosinophil cationic protein (ECP) of serum to distinguish different allergic reactions. In one group of patients with food intolerance symptom-induced challenge resulted in a marked decrease of serum-ECP. The number of blood eosinophils decreased simultaneously in some but not all of these patients. In another group of patients with food intolerance serum-ECP displayed peak-like increases followed by a decrease. The decrease in serum-ECP may reflect that consumption of ECP is a result of idiosyncrasy in the target organ. In allergic rhinitis some patients showed an initial peak-like increase of serum-ECP, which was abolished by pretreatment with disodium-cromoglycate but not by pretreatment with antihistamine. Similar results have previously been demonstrated for allergic asthma. The difference obtained in serum-ECP upon challenge in typical reagin-mediated allergy and food intolerance may indicate that the latter is not reagin-mediated. However, the interpretation of data is difficult because of lack of knowledge regarding the turnover in the circulation of ECP.

Adult↗

Pheochromocytoma of the bladder. A case report.

A 39-year-old male patient with attacks of headache and tachycardia immediately after micturition is described. Systolic blood pressure of 250 mmHg was measured after voiding. Plasma noradrenaline was increased 10 to 20 times above the normal value during the attacks. Cystoscopy, arteriography, catheterization of the caval vein with sampling for plasma catecholamines and computerized tomography all supported the diagnosis of a bladder tumour. A beneficial effect of alpha-receptor blockade preoperatively was demonstrated. The tumour was operatively removed from the bladder. The postoperative course was uneventful.

Adult↗

Plasma catecholamine levels in the diagnosis and management of pheochromocytoma.

Plasma catecholamine levels have been determined before, during and after operation in seven consecutive patients operated upon for pheochromocytoma. The method used permits the simultaneous determination of norepinephrine, epinephrine and dopamine. All patients had increased levels of one or several catecholamines while hypertensive. Two of seven patients had normal levels of catecholamines while they were normotensive. Spontaneous or provoked attacks strongly increased plasma catecholamine levels. The present method may prove to be of value as a simple method to ascertain or exclude pheochromocytoma. During operation plasma norepinephrine and epinephrine levels increased up to 600fold when the tumor was manipulated. The unpredictable rapid and large variations in levels of catecholamines found during operation suggest preoperative alpha-adrenergic receptor blockade and monitoring of central circulation.

Adolescent↗

Growth hormone and prolactin production in human pituitary tumours in organ culture.

Human pituitary adenomas, when preserved as organ cultures do not lose their function of synthesizing and releasing hormone. Thus, growth hormone producing adenomas have been cultured for 35 days and prolactinomas for 14 days with maintained hormone hypersecretion, > 30 000 pmol/l/48 h of growith hormone and > 15 000 micrograms/l/48 h of prolactin. Preserved morphology/ultrastructure was documented in these specimens. Following repeated renewal of the entire nutrient solution, less than 1/10 of the initial hormone content remained after the first change, indicating an active hormone production/release into the culture medium as hormone concentration rose to previous levels. The growth hormone producing cells could be stimulated by TRH and LH-RH in the concentrations 10(-8) and 10(-7) g/l respectively, indicating the same pathological reactivity in vitro as in vivo. Prolactin synthesis in vitro paralleled that in vivo, as reflected by serum prolactin levels. Growth hormone synthesis in vitro paralleled the clinical activity of the disease, but the plasma hormone levels in patients with acromegaly did not do so.

Adenoma↗

[Surgical management of pituitary adenomas with preservation of pituitary function (author's transl)].

Tumors of the pituitary gland comprise a large group of the intracranial tumors. As in all tumor surgery, early diagnosis is essential for the best outcome of treatment. However, the non-functioning adenomas are often diagnosed in their later stages of development as a result of the complexity of symptoms due to a mass lesion. In contrast, hormone-secreting adenomas give early symptoms which can be supported by reliable diagnostic laboratory findings and involve the production of growth hormone, prolactin and ACTH respectively. Using the transantro-sphenoidal route, our results of surgical removal of small tumors have been excellent, and microadenomas have been treated with preservation of normal pituitary function. However, an increasing size of the tumor considerably reduces the possibility of cure.

Adenoma↗

Occurrence of pituitary adenomas and other neoplastic diseases in primary hyperparathyroidism.

One hundred and forty-seven consecutive patients with primary hyperparathyroidism operted upon during the period of 1973 to 1978, have been studied with regard to incidence of neoplasms--malignant lesions, pituitary tumors and other benign tumors. The incidence was compared with that published in the Swedish Cancer Registry, which has been in existance since 1958. Patients who had undergone a cholecystectomy were used as another control group. The patients with primary hyperparathyroidism demonstrated 24 malignant tumors in a variety of organs, denoting an incidence of almost twice that calculated according to the Cancer Registry and that found in the control group. Sixteen instances of tumors of the pituitary were found--eight with hypersecretion of one or two pituitary hormones and eight with nonfunctioning adenomas. The incidence of neoplasms for the patients with primary hyperparathyroidism was 40, the expected incidence being 13. The neoplasms were predominant in the women. The data demonstrate that patients with primary hyperparathyroidism run an increased risk of having neoplasms develop. These may be encountered antecedant to, concomitant with or subsequent to the diagnosis of primary hyperparathyroidism.

Adenoma↗

Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. Mitochondrial protein synthesis and analysis of the polypeptide composition of cytochrome c oxidase.

Three previously isolated mutants of Neurospora crassa, temperature-sensitive for the production of cytochrome aa3, have been further analyzed. These mutants have a slightly reduced capacity for mitochondrial protein synthesis when grown at 41 degrees C, although this relative deficiency appeared to be no greater than the deficiency in other cytochrome-aa3-deficient mutants. Thermolability studies revealed that the cytochrome c oxidase purified from each of the mutants grown at 23 degrees C is no more sensitive to heat inactivation than the enzyme isolated from wild-type cells. Sodium dodecylsulfate gel electrophoresis of immunoprecipitates obtained from the mitochondria of each of the mutants grown at 23 degrees C, using antiserum directed against holocytochrome c oxidase, indicated that all the subunits of cytochrome c oxidase were present in relative amounts similar to those found in mitochondria from wild-type cultures. However, when the mitochondria from mutant cultures grown at 41 degrees C were examined in the above fashion, only subunits 5 and 6 of the oxidase were detected. Nonetheless, the mitochondrially synthesized subunit 1, 2 and 3 polypeptides could be immunoprecipitated from mitochondria isolated from mutant cells grown at 41 degrees C and labelled with [3H]leucine in medium containing cycloheximide. Although subunits 4 and 7 could not be detected, because a suitable antibody was not available, the fact that five of the seven subunits were present, but not associated with each other, suggested that the genetic defects in these mutants may affect the process of cytochrome c oxidase assembly.

Electron Transport Complex IV↗

Cytochrome c oxidase subunits in nuclear and extranuclear cytochrome-aa3-deficient mutants of Neurospora crassa.

The mitochondria of cytochrome-aa3-deficient Neurospora crassa mutants were screened for the seven polypeptide constiuents of cytochrome c oxidase. The polypeptides of the holoenzyme and the unassembled or partially assembled subunits were detected by sodium dodecyl sulfate/acrylamide gel electrophoresis of immunoprecipitates obtained with antiserum to the holoenzyme as well as to several individual subunits. With respect to the mitochondrially synthesized polypeptides of the oxidase, subunits 1 to 3, the results obtained from the analysis of immunoprecipitates were confirmed through the direct electrophoretic analysis of mitochondrial translation products. The results were as follows. 1. The mitochondria of the cya-2-8 and cya-3-16 nuclear mutants and the [exn-5] cytoplasmic mutant contained a protein complex immunoprecipitated by anti-holoenzyme antibody and composed of the complete set of the seven cytochrome oxidase polypeptides. Only the oxidase subunits 5 and 6 were immunoprecipitated by anti-holoenzyme antibody from the mitochondria of the cyt-2-1 and 299-1 nuclear mutants, even though at least some of the mitochondrially synthesized polypeptides were detected in both mutants by subunit specific immunoprecipitation. 2. A 'subunit 1' polypeptide larger than the authentic subunit-1 polypeptide of wild-type cytochrome oxidase was found in the mitochondria from two nuclear mutants, cyt-2-1, and 299-1 and the [mi-3] cytoplasmic mutant. This larger polypeptide may be an unprocessed precursor of the 'mature' subunit 1 protein of the holoenzyme. No changes in the apparent molecular weights were found for the polypeptide subunits of cytochrome oxidase in mitochondria of the [exn-5] cytoplasmic mutant and the cya-2-8 and cya-4-23 nuclear mutants. 3. A nuclear mutant, 299-1, lacks the mitochondrially synthesized subunit-2 polypeptide of cytochrome oxidase. When cells were labelled in the presence of cycloheximide, the subunit 2 content of mitochondria from mutants [exn-5], cya-2-8, cya-3-16 and cya-4-23 was lower than in mitochondria from wild-type. This deficiency, however, does not appear to be sufficiently severe to fully account for the lack of cytochrome aa3 in these mutants. The cya-4-23 nuclear mutant either is severely deficient in or lacks cytochrome oxidase subunits 5 and 6. On the basis of these and previously reported observations, it is proposed that the cytochrome oxidase deficiencies of as many as seven of the eight N. crassa cytochrome-aa3-deficient mutants could be caused by genetically imposed alterations in regulatory systems controlling the production of different components of the enzyme.

Cytochromes↗

Conversion of a mitochondrial precursor polypeptide into subunit 1 of cytochrome oxidase in the mi-3 mutant of Neurospora crassa.

1. The cytochrome-alpha alpha 3-deficient mi-3 cytoplasmic mutant of Neurospora crassa synthesizes a mitochondrial translation product which crossreacts with antibodies specific to subunit 1 of cytochrome oxidase. The immunoprecipitated polypeptide migrates more slowly during gel electrophoresis than the authentic 41 000-Mr subunit 1 of the wild-type enzyme. An apparent molecular weight of about 45 000 was estimated for the mutant product. 2. Radioactive labelling experiments in vivo show that the crossreacting material found in the mutant is relatively stable and does not form complexes with other subunits of the oxidase. 3. After induction of a functional cytochrome oxidase in the mutant cells with antimycin A, the 45 000-Mr polypeptide is converted to a 41 000-Mr component, which exhibits the same electrophoretic mobility as subunit 1 of the oxidase. Pulse-chase labelling kinetics reveal a typical precursor product relationship. 4. The converted polypeptide becomes assembled with other enzyme subunits to form a protein complex which has the immunological characteristics of cytochrome oxidase. A possible physiological role of the post-translational processing of the mitochondrially synthesized component is discussed.

Cross Reactions↗