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Biomedical subjects

R Finke

Publications and source records attributed to R Finke.

At least 55 records · Page 3Linked to original sources

The auricular myocardiocytes of the heart constitute an endocrine organ. Characterization of a porcine cardiac peptide hormone, cardiodilatin-126.

A peptide hormone was extracted from the porcine right atrium following a bioassay for differential vasorelaxant effects on smooth muscle strips from aorta and renal and inferior mesenteric arteries. The isolation procedure included several steps of gel-permeation and ion-exchange chromatography, and high performance liquid chromatography. During the isolation procedure, other peptides of smaller molecular weight were also found, which, in relation to cardiodilatin-126 (CDD-126), are shorter at their N-terminal. Among these, CDD-88 has also been isolated and characterized, and has been established as a prominent member of the cardiac hormone family. The N-terminal and C-terminal segments of the 126 amino acid-containing molecule were synthesized and used to raise region-specific antibodies. The natural peptide was then localized within myoendocrine cells of the right atrium where specific atrial granules are located. Renal effects of cardiodilation were studied in conscious dogs and showed strong diuretic and natriuretic activities. According to our functional studies, cardiodilatin-126 and cardiodilatin-88 possess qualities of a significant hormone family regarding the regulation of extracellular fluid volume and blood pressure.

Amino Acid Sequence↗

10 years experience with consecutive measurement of thyrotropin binding inhibiting antibodies (TBIAb).

In the present study we reviewed 230 patients in whom thyrotropin-binding inhibiting antibodies (TBIAb) follow-up determinations had been performed up to 10 yr after hyperthyroidism had first developed. In 104 patients, Graves' ophthalmopathy occurred at some time in the course of the observation period. Fourty-four of these patients with Graves' ophthalmopathy had at least one, and up to four relapses after each one-year course of antithyroid drug therapy with methimazole. The addition of TBIAb-positive results over an observation period of 1-10 yr showed positive cumulative findings in 95% of the 44 patients with recurrences of Graves' disease. A single TBIAb determination during hyperthyroidism showed positive results in 70%. A detailed breakdown showed that TBIAb was detectable during all hyperthyroid phases in 48% of the patients with ophthalmopathy. Thirty-four per cent of the patients had sometimes positive, sometimes negative TBIAb findings in the various hyperthyroid states. In 18% of the patients, TBIAb was not detected in any of the hyperthyroid phases. However, some of these patients became TBIAb-positive for the first time during antithyroid drug therapy or during a remission confirmed by a suppression test. Only 2 of the 44 patients never had TBIAb positive results at any time during the observation period. In those patients without ophthalmopathy during the observation period, the "cumulative" frequency of TBIAb was 74% for patients with diffuse goiter and 52% for patients with diffuse-nodular goiter. However, in patients with ophthalmopathy, there was no difference in TBIAb detectability between those patients with a diffuse and those with a diffuse-nodular thyroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Methodological aspects and clinical results of an assay for thyroid-stimulating antibodies: correlation with thyrotropin binding-inhibiting antibodies.

Several methodological aspects concerning the measurement of thyroid-stimulating antibodies (TSAb) were examined using a 5000-g particulate fraction from human thyroid tissue. TSH displayed maximal stimulation at 32 C. An ATP-regenerating system had no influence at ATP concentrations greater than 0.67 mM. Theophylline did not influence cAMP concentrations in the incubation medium after stimulation with increasing dosages of TSH, suggesting the absence of active phosphodiesterases in the membrane preparations. Sera dialyzed against Tris-HCl were as suitable as immunoglobulin G preparations for determination of TSAb. One hundred and nineteen patients with ophthalmic Graves' disease, 42 of whom were hyperthyroid at the time of study, were investigated for TSH binding-inhibiting antibodies ( TBIAb ) and TSAb. In 76% of these patients, concordance between the presence and absence of both activities was found independent of whether they were untreated, treated, or in remission. When gradations of potency in the two systems were compared, linear regression revealed a correlation coefficient of 0.59. The coefficient correlation increased when TBIAb and TSAb were each determined in a single assay using identical thyroid membrane preparations. In four other patients, both TSAb and TBIAb were measured repeatedly during the course of the disease. In three patients, both activities were parallel, whereas in one patient, dissociation of the two activities was found. The data suggest the presence of antibodies with varying stimulating and binding-inhibiting properties. However, in hyperthyroidism of Graves' disease, both activities usually were present in similar quantities.

Adenylyl Cyclases↗

Threshold pressure for the pressure-dependent renin release in the autoregulating kidney of conscious dogs.

The effect of varying renal artery pressure between 160 and 40 mm Hg on renal blood flow and renin release was studied in seven conscious foxhounds under beta-adrenergic blockade receiving a normal sodium diet (4.1 mmol/kg/day). Pressure was either increased by bilateral common carotid occlusion or reduced in steps and maintained constant by a control-system using an inflatable renal artery cuff. Carotid occlusion itself had no influence on renal blood flow and renin release when renal artery pressure was kept constant and the beta-receptors in the kidney were blocked. Between 160 mm Hg and resting pressure there was no change in renal blood flow; between resting blood pressure and the lower limit of autoregulation (average 63.9 mm Hg) renal blood flow increased slightly (average 7%) indicating a high efficiency of renal blood flow autoregulation. The relationship between renal artery pressure and renin release could be approximated by two linear sections: a low sensitivity to a pressure change (average slope: -0.69 +/- 0.26 ng AI/min/mm Hg) was found above a threshold pressure (average: 89.8 +/- 3.3 mm Hg) and a high sensitivity to a pressure change (average slope: -64.4 +/- 20.8 ng AI/min/mm Hg) was observed between threshold pressure and 60 mm Hg. There was no further increase of renin release between 60 and 40 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

HLA-DR3 and HLA-DR5 associated thyrotoxicosis--two different types of toxic diffuse goiter.

One hundred fifty patients with toxic and scintigraphically diffuse goiter were HLA typed (A, B, C, DR). One group consisted of 101 patients with concomitant Graves' ophthalmopathy and/or TSH-binding inhibiting antibodies (TBIAb). Forty nine patients had neither ophthalmopathy nor TBIAb. The former group showed a higher prevalence of HLA-B8 and DR3 compared to a normal control group. The latter group showed a higher frequency of HLA-DR5, whereas the HLA-B8 and DR3 antigens were slightly below normal prevalence. These data indicate an immunogenetic heterogeneity in patients with toxic diffuse goiter. A group of 47 hyperthyroid patients with single autonomous thyroid adenoma had no increased prevalence of any HLA-antigens. Patients with long term remission did not show an altered prevalence of any of the HLA antigens compared to controls. In contrast, patients with Graves' ophthalmopathy and/or TBIAb activity who relapsed had a significantly higher prevalence of HLA-B8 DR3, whereas patients without TBIAb and eye signs who relapsed had a significantly higher prevalence of HLA-DR5 than the control group.

Graves Disease↗

Circulating TSH-binding inhibiting immunoglobulins in myasthenia gravis.

Using a radioligand receptor assay the sera of 46 patients with myasthenia gravis (MG) were tested for the presence of circulating TSH-binding inhibiting immunoglobulins (TBII). In addition thyroid function was evaluated on the basis of T3, T4, TBG and TSH radioimmunoassays including the TRH stimulation test. Circulating antimicrosomal and antithyroglobulin thyroid antibodies were measured by haemagglutination techniques. Two patients had concomitant Graves' disease (GD), 5 were euthyroid with autonomously functioning thyroid tissue due to non-immunogenic multinodular goitre and 39 myasthenic patients were euthyroid with normal pituitary thyroid axis. Only 1 patient with GD had strongly positive TBII-activity and 3 euthyroid MG patients were TBII borderline-positive.

Adolescent↗

[Clinical importance of the estimation of thyrotropin displacing antibodies (author's transl)].

In 69 hyperthyroid patients with diffuse uptake in the scintigram, thyrotropin displacing antibodies (TDA) were measured before, during and after thyrostatic treatment. In a further 42 patients antibody activity was investigated before and 6-12 weeks after radio-iodine treatment, and in 29 patients it was measured before and after subtotal thyroidectomy. Persistence of demonstrable TDA during and after the end of drug treatment was in all cases indicative of recurrence of hyperthyroidism. On the other hand, disappearance of TDA activity was not a guarantee for prolonged remission as five patients had a recurrence despite loss of TDA activity. In a further nine patients hyperthyroidism reappeared with recurrence of TDA after varyingly long periods of remission. Thyrostatic treatment should be performed until disappearance of antibodies. Prolonged demonstration of TDA should lead to surgical intervention. Besides the usefulness in establishing the diagnosis of immunogenic hyperthyroidism (Graves' disease) TDA estimation may be of some prognostic value in the use of thyrostatics. In contrast, after radio-iodine treatment or operation the functioning capacity of the remaining thyroid tissue seems to be more relevant for the success of treatment than the possibly longer acting antibodies.

Antibodies↗

Mitogenic response of peripheral blood lymphocytes from patients with Graves' disease incubated with solubilized thyroid cell membranes containing TSH receptor and with thyroglobulin.

Transformation of peripheral blood lymphocytes (PBL) in response to solubilized TSH receptor and to human thyroglobulin (hTG) was carried out in patients with Graves' disease (GD). Mean stimulation index (SI) in response to solubilized TSH receptor was significantly increased only in hyperthyroid GD patients (SI = 3.0 +/- 1.8 SD, n = 13, p less than 0.025) when compared to normal subjects (SI = 1.5 +/- 0.8 SD,n = 14). All other subgroups of GD patients (i.e., euthyroid GD patients after treatment as well as those with/without ophthalmopathy or TSH-displacing antibody [TDA]) showed a tendency to elevated mean SI, which, however, was never significantly increased. In contrast, patients who were suspected of having a "disseminated autonomy" showed a tendency to decreased mean SI compared to GD patients. The mitogenic response of PBLs induced by solubilized TSH receptor could be suppressed by incubation of antigen and PBLs with bTSH. Control experiments with purified protein derivate of tuberculin(PPD) as stimulating antigen revealed, however, that bTSH itself suppresses the mitogenic response of PBLs and that the decrease of SI in this experiment is not due to blockage of the antigenic determinants of the TSH receptor protein. Human thyroglobulin (hTG) produced no significant increase in the SI of PBLs. Only 9 out of 47 GD patients showed an SI higher than the mean of normals + 2 SD. All those patients, however, who showed an elevated SI ( greater than 2.0) also revealed an increased SI with solubilized TSH receptor.

Cell Membrane↗

TSH-receptor antibodies, HLA B8 and thyroid autoantibodies in patients with Graves' disease in therapeutically induced euthyroidism.

The prevalence of TSH-receptor antibodies and of thyroid autoantibodies was studied in 48 HLA-typed patients with Graves' disease, who were in an euthyroid state after antithyroid therapy with methimazole. TSH-receptor antibodies, which were found in 35% of the patients, did not correlate with the positivity of HLA B8. By contrast the persistence of thyroid microsomal antibodies was significantly associated with HLA B8.

Antibodies↗

Relationship between thyroid status and Graves' disease-specific immunoglobulins.

The prevalence of TSI in Graves' disease was investigated with a radioligand receptor assay using human thyroid membranes and highly purified labeled porcine TSH or bovine TSH in 110 patients before treatment and in 39 patients after successful treatment with antithyroid drugs. In 11 patients, the assay was performed before, during, and after therapy. The results in the radioligand receptor assay were compared to thyroid function tests (TRH test, free T4 index, serum %3 level, and thyroid suppression test). Normal IgG inhibits nonspecifically, but dose dependently, the binding of [125I]TSH to thyroid membranes. IgG samples from patients were only considered to be positive if they reduced the binding of the labeled hormone below the mean value minus 2 SD of the controls. TSI activity was found in 50% of the patients with untreated diffuse toxic goiter, in 3 out of 27 cases who regained suppressible thyroid function, and in 5 out of 12 cases who were off therapy for more than 6 weeks and showed normal TRH tests and normal hormone levels but in whom the suppression test was not performed. Our data cannot prove the hypothesis that only humoral antibodies are responsible for the thyroid stimulation in Graves' disease, but of course they cannot exclude it; furthermore, they suggest the existence of antibodies which bind to the human thyroid cell membrane without necessarily stimulating thyroid cellular activity.

Antigen-Antibody Complex↗

Experimental coronary artery bypass operation. Myocardial blood flow, ventricular performance and regional myocardial function.

Myocardial blood flow and ventricular function was studied in seven dogs with chronic myocardial ischemia before and after coronary bypass grafting. Restoring blood flow in an area of 25% of the anterior wall of the left ventricle did not significantly improve overall ventricular function. Assessment of intramyocardial pressure as an index of regional myocardial function revealed a consistent enhancement of myocardial contraction at rest, and under pharmacological stress of the heart.

Animals↗

[Myocardial blood flow and ventricular function in dependence on the size of myocardial infarct].

In eight dogs three branches of the left anterior descending coronary artery were occluded by successive ligations. Each time coronary flow reserve was measured by injecting dipyridamole (0.4 mg.kg-1). After an infarction of 13% of the left ventricle there was a significant decrease of Vmax and dp/dtmax (p less than 0.05). Measurements of regional myocardial blood flow detected an infarction of 5% of the left ventricle, whereas the total myocardial blood flow was reduced significantly when 17% of the left ventricle was infarcted.

Animals↗

[Regional myocardial blood flow and left ventricular function in critical coronary stenosis and after coronary artery bypass grafting in the dog (author's transl)].

In 7 mongrel dogs myocardial ischemia is produced by means of an ameroid constrictor placed on the left circumflex coronary artery (CCA). Myocardial blood flow (MBF) is diminished by 56% in an area of 25% of the anterior wall of the left ventricle. A decrease in dp/dtmax suggests a small depression of left ventricular function. After bypass operation the slight changes in EDP, dp/dtmax and Vmax indicate no significant improvement of total ventricular function. MBF increases from 42 +/- 10 ml/100 g/min to 67 +/- 21 ml/100 g/min (p smaller than 0.02) in the area supplied by the bypass. In this region intramyocardial pressure rises significantly suggesting improvement of regional myocardial function.

Animals↗