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R D Hesch

Publications and source records attributed to R D Hesch.

At least 145 records · Page 8Linked to original sources

Preliminary results on the use of an antiserum to human parathyrin in a homologous radioimmunoassay.

A new antiserum (Ab Giselle) raised in sheep against extracted human parathyrin was evaluated and compared with an established antiserum (Ab S-478 VI) under several test conditions. The assay system contained an extracted 1--84 human parathyrin standard and a 1--84 bovine parathyrin tracer. The total assay time was 24 h and the main assay characteristics as follows: B0/T 0.28 +/- 0.02 and 50% intercept 553 +/- 47 U . 1(-1). The corresponding data for Ab S-478 VI were: B0/T 0.23 +/- 0.02 and 50% intercept 890 +/- 142 U . 1(-1). The normal range in 152 normocalcaemic volunteers (age range 16--67 years) was 10.6--423 U . 1(-1) (where 1 vial MRC reference preparation 75/549 for human parathyrin = 25 U), compared with 0--300 U . 1(-1) for Ab S-478 VI. With the new antiserum, differentiation between hypoparathyroid patients and those with normal function was often possible, and differentiation between normal and elevated levels, as in hyperparathyrinaemia, was very good. Correlation between Ab Giselle and Ab S-478 VI in 80 normal volunteers was positive (r = 0.450, p = 0.01) although the regression line showed that the antisera had different specificities (data for the regression line y = a + bx, a = 0.13, b = 0.55). Under the assay conditions, the association constant for Ab Giselle was 0.41 +/- 10(14) l . mol-1 in contrast to Ab S-478 VI which had a Ka for 0.53 x 10(10) l . mol-1 under identical conditions. Assays using Ab Giselle could be performed at room temperature, whereas those using Ab S-478 VI performed best at 0 degrees C. Preliminary results suggest that Ab Giselle is better for the routine assay of human parathyrin in serum than Ab S-478 VI, especially in the case of hypoparathyroid patients.

Adenoma↗

Adsorption of parathyrin: pitfall for solid phase assays using radiolabelled antibodies?

The physicochemical behaviour of parathyrin on surfaces was investigated. Parathyrin is bound to the wall of polyethylene, polypropylene and flint glass tubes. This adsorptive binding of the hormone, detected by labelled antibodies, is a time-dependent process which is complete within one hour. The addition of plasma decreases but does not prevent adsorption. Coating of the tubes with an anti-N-regional or anti-C-regional antiserum decreases the sensitivity of the detection of 1-34, 53-84 and 1-84 intact parathyrin, when performed in buffer. In the presence of plasma the increase of radiolabelled antibody detecting the parathyrin was more pronounced when tubes were precoated with an anti-parathyrin antibody. The sensitivity of the 1-84 parathyrin assay was also reduced when incubation was carried out in the presence of high concentrations of parathyrin-fragments, calcitonin, somatostatin or bovine serum albumin. Assay specificity seems to be related to the specificity of the labelled antibody for the respective hormonal fragment, not to that of the antibody used for coating the tubes. This investigation illustrates the necessity for the careful control of parathyrin assay conditions, e. g. non-specific binding of native parathyrin and radiolabelled tracers to laboratory reaction vessels.

Adsorption↗

[Clinic and pathophysiology of osteopathies (author's transl)].

Results of this paper have shown via pathophysiological examples that rapid progress has been made in our pathophysiological concepts regarding the causal and formal genesis of osteopathy. Systematic organization of these concepts facilitates understanding and communication between the radiologist and the clinician. There is a marked contrast between this fact on the one hand and our lack of knowledge in the clear diagnostic description of osteopathies with the exception of hyperparathyroidism on the other. Important advances in current radiological research are represented by the radiologically subtle formal description of topographically relevant changes and quantitative analyses of the mineral salt content. However, at this stage we are unable to predict as to how quantification of the osseous mass will be successfully achieved in the near future. Scientific co-operation between radiologists and clinicians should be promoted and accelerated, since better on-target diagnosis is imperative, both from the viewpoint of sociomedicine and from that of epidemiology, in the case of metabolic disorders, which are essentially involved in increasing the morbidity of the entire population.

Androgens↗

[On the clinical value of roentgenological observation of the clinical course of renal osteopathy (author's transl)].

Basing on radiological observation of the course of renal osteopathy confirmed both clinically and by bone biopsy in 96 patients -- the x-ray examination comprising primarily the entire axial skeleton including the proximal extremities and hands -- 60% of the patients showed mineralisation in their hands. The rest of the skeleton was affected only if there were identifiable alterations at the hands, although the affection of the axial skeleton was definitely lower in terms of percentage. Hence, radiological observation of renal osteopathy based on x-ray films of both hands with additional magnification technique appears both possible and meaningful.

Adolescent↗

[Causes of inner ear deafness; a critique of therapy (author's transl)].

In spite of recent criticisms, the diagnosis of inner ear hearing impairment is based on both pure tone thresholds and suprathreshold tests. The acoustico-facial reflex is useful only when used in conjunction with the suprathreshold tests.--Noise-induced deafness is generally confined to the higher frequencies of sound, and only exceptionally involve the middle frequencies as well. Low-tone hearing impairment may represent a partial symptom of Meniere's Disease as well as functional hearing loss. Zoster oticus produces a sensory hearing impairment but not a neural one, as might be expected from the neurotropy of the Herpes virus. Patients with socalled presbyacusis exhibit criteria of inner ear pathology which may represent a summation of different noxious agents damaging the inner ear throughout life rather than result from the physiologic process of aging. Traumatic hearing impairment seldom progresses, and usually involves central parts of the auditory pathways following blunt trauma.--We believe that uncritical therapy with vasodilating drugs is not useful in sensory hearing loss, especially if it is continued for months and if several drugs are employed at the same time. The danger of an unintended decrease in blood pressure is greater in these patients since many also suffer from hypotension which can then cause vascular insufficiency to the inner ear, similar to the "steal" effect. Therapy for inner ear hearing loss remains the responsibility of the otolaryngologist, and should still be based on proper diagnosis.

Audiometry↗

[Treatment of dopamine-dependent shock with triiodothyronine: prelimary results (author's transl)].

Triiodothyronine (T3) was administered to 11 patients in septic shock. In all there occurred an increase in arterial blood pressure within 24 hours, the rise in systolic pressure being 34 +/- 4.2 mm Hg, of diastolic 14 +/- 8.2 mm Hg, corresponding to a rise in mean arterial pressure of 25 +/- 6.1 mm Hg. Haemodynamic studies in four patients suggest that the action of T3 is mediated via beta-sympathomimetic channels.

Blood Pressure↗

Binding of bovine parathyroid hormone to surface receptors of cultured B-lymphocytes.

Binding of parathyroid hormone onto B-lymphocytes is detected by the utilization of the labelled antibody membrane assay. The amount of parathyroid hormone bound to the receptor sites was depending on the quantity of cells in the incubation milieu. Each cell line showed typical characteristics in time course of parathyroid hormone binding and maximal receptor capacity. Fragmentation of intact parathyroid hormone, also varying with the cell line tested, was very rapid, even at 24 degrees C. Within 20 min most of the cell lines destroyed 20% of the native hormone in the incubation mixture, indicating a fragmentation rate of up to 2.25 ng/min at 37 degrees C. Bmax and KD for the different lymphocytes was 5.3--19 . 10(11) M and 1.8--18,5 . 10(11) M, respectively. These values are in the range of reported plasma concentrations and may therefore represent more physiological values for the capacity and affinity of membrane receptors.

Animals↗

Re-examination of the subcellular localization of thyroxine 5'-deiodination in rat liver.

We describe the existence of at least two thyroxine 5'-deiodinases in rat liver. They co-fractionate with NADPH-cytochrome c reductase, the marker enzyme for membranes of the endoplasmic reticulum. Subcellular-localization studies of the most active microsomal thyroxine 5'-deiodinase were performed under substrate saturation and at optimal pH 6.8. This enzyme was a Km(app.) of about 3 microM-thyroxine and a Vmax. of about 8 ng of tri-iodothyronine/min per mg of protein. Our study confirms in part the earlier reports of microsomal localization of thyroxine 5'-deiodination. However, this process is not mediated by only a single enzyme.

Animals↗

[On the question of cortisol administration in adrenocortical insufficiency (author's transl)].

The question whether clinically normal adrenal cortical function can be satisfactorily checked by laboratory studies during substitution treatment with adrenocortical hormones was investigated in 39 patients with adrenal insufficiency. The routine measurement of serum cortisol levels (2 to maximally 7 hours after the morning dose of hydrocortisone or cortisone acetate) revealed marked individual variations which were relatively independent of the morning dosage. Similar extreme variations were found for free urinary corticoids in 24-hour urine. Both values could not be correlated with the clinically individualised and satisfactory long-term substitution dosage and cannot be used, therefore, in the customary manner to assess a normal hormonal state. It appears unlikely that such information can altogether be obtained from plasma levels.

Adolescent↗

Regulatory hyperparathyroidism in a pig breed with vitamin D dependency rickets.

A radioimmunoassay for porcine parathyroid hormone has been developed and applied to measure immunoreactive parathyroid hormone (PTH) in plasma of pigs with hereditary vitamin D dependency rickets (VDDR) (pseudovitamin D deficiency rickets). Levels of 25-hydroxycholecalciferol (25-(OH)-D3) in plasma were measured by a protein binding assay. Both plasma concentrations of PTH and 25-(OH)-D3 showed an approximately 4-fold increase compared to normal pigs. PTH levels increased with duration of the disease. Daily dosing of the animals with 1--4 micrograms of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) reduced PTH concentrations and resulted in clinical healing. Iv administration of 10 micrograms of 25-(OH)-D3/day did not alter PTH concentrations nor the clinical symptoms. The results suggest that these animals suffer from regulatory hyperparathyroidism. The metabolic defect could be due to a failure of the kidney to convert 25-(OH)-D3 to 1,25-(OH)2-D3.

Animals↗

Autoantibodies to parathyroid hormone receptor.

Autoantibodies which block the binding of parathyroid hormone to membrane receptors for the hormone were detected in the sera (especially in the IgG fraction) of 49 out of 50 uraemic patients with secondary hyperparathyroidism (patients with high levels of C-regional parathyroid hormone). These antibodies are species-specific. Their presence in the serum in unaffected by dialysis. Inhibition of binding appears to be related to the rise in C-regional parathyroid-hormone levels and the duration of uraemia. The production of cyclic adenosine monophosphate by parathyroid-hormone-stimulated adenyl cyclase was reduced by the blocking antibodies. The findings show that secondary hyperparathyrodism in uraemia is another example of a receptor-antibody disease, but it is not known whether the antibodies act by modifying the affinity of the receptors for the hormone or by reducing the concentration of receptors available.

Animals↗

Conversion of T3 and rT3 to 3,3'-T2: pH dependency.

In the extrathyroidal deiodination of T4 the importance of T3 and rT3 for the peripheral action of thyroid hormones is well documented. With the development of a specific radioimmunoassay for 3,3'-T2, a deiodination product of both T3 and rT3, we were able to characterize these subsequent enzymatic reactions as well as the degradation of 3,3'-T2 in rat liver homogenate. It was found that the reaction T3 leads to 3,3'-T2 is slow compared to the conversion of T4 to T3. The pH activity profile shows a peak at 8.4. The reaction rT3 leads to 3,3'-T2 is very fast, with an apparent KM of 4 x 10(-7) M. The reaction velocity is significantly higher in acid than in alkaline pH. The deiodination of 3,3'-T2 is also faster in the acid than in the alkaline range. It is concluded that the outer ring of T4 is more readily deiodinated in acid and the inner ring in alkaline media, and that 3,3'-T2 is mainly degraded to 3-T1. In the acid pH range T3 may accumulate and in the alkaline range rT3 by the pH characteristics of these ractions. Therefore small shifts in pH can enhance the potent inhibitory action of rT3 on the 5'-deiodination of T4 adding another mechanism to the peripheral regulation of thyroid hormone activity.

Animals↗

[Screening for neonatal hypothyroidism? Results of an international questionnaire study (author's transl)].

Questionnaires were sent to 23 centres in ten countries. Results indicate that, for ethical, scientific, clinical and socio-economic reasons, screening for neonatal hypothyroidism should be undertaken. Pilot studies are no longer required. Distribution of the birth-rate in the various lands of the German Federal Republic suggest that, assuming appropriate technical and staffing provision, ten centres with a sample rate of 200/day would be sufficient for full screening. Because of special features in quality control of radioimmunochemical methods, a uniform manner of setting up the necessary laboratories is essential.

Congenital Hypothyroidism↗

Regulation of thyroid hormone metabolism in rat liver fractions.

The nature of the conversion of thyroxine (T4) to triiodothyronine (T3) and reverse triiodothyronine (rT3) was investigated in rat liver homogenate and microsomes. A 6-fold rise of T3 and 2.5-fold rise of rT3 levels determined by specific radioimmunoassays was observed over 6 h after the addition of T4. An enzymic process is suggested that converts T4 to T3 and rT3. For T3 the optimal pH is 6 and for rT3, 9.5. The converting activity for both T3 and rT3 is temperature dependent and can be suppressed by heat, H2O2, merthiolate and by 5-propyl-2-thiouracil. rT3 and to a lesser degree iodide, were able to inhibit the production of T3 in a dose related fashion. Therefore the pH dependency, rT3 and iodide may regulate the availability of T3 or rT3 depending on the metabolic requirements of thyroid hormones.

Animals↗