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Biomedical subjects

R D Hesch

Publications and source records attributed to R D Hesch.

At least 163 records · Page 9Linked to original sources

Endocrinological aspects of PTH metabolism in the kidney.

Various methods for the measurement of intact PTH, PTH fragments and PTH binding to receptors were applied to clarify the role of renal receptors for the bioexpression of PTH. Glomerular receptors may contribute approximately 20% of the renal PTH catabolism. PTH also binds to tubular receptors at the luminal side (brush border membranes) as well as at the antiluminal site (basal-lateral membrane). Scatchard plot analysis of PTH binding to these receptors allows the calculation of an equilibrium dissociation constant and binding capacity, if correction is made for inactivation of bioactive PTH (measured by LAMA). Binding to receptors is--in our systems--invariably associated with degradation of the intact hormone to N-terminal and C-terminal fragments of different molecular weight. Antibodies against basal lateral membranes and against brush border membranes are able to inhibit PTH binding to tubular membranes. Sera of uremic patients with inappropriately high PTH contain a globulin which interferes with PTH binding to the receptor, suggesting that uremia may be another example for a "hormone receptor antibody disease".

Animals↗

Kinetics of PTH metabolism and PTH fragments in chronic renal failure.

Distribution and metabolic degradation of bPTH was studied in man after infusion of 400 U bPTH and blood sampling up to 2h. Disappearance rates of intact 1-84 bPTH, carboxyl- and amino-regional peptides were calculated for healthy subjects (n = 12); patients suffering from moderate (GFR 15--30 ml/min, n = 4) and advanced (GFR less than or equal to 10 ml/min, n = 36) chronic renal failure; and bilateral nephrectomized patients (n = 3). Two components with a rapid and a slow disappearance rate can be separated ("distribution", "metabolism"). Half-lives are found to be in the range known from animal experiments with marked differences between intact 1-84 PTH and peptide fragments. Influence of impaired renal function on metabolic turnover rates of PTH is given.

Alkaline Phosphatase↗

[Histomorphometric study of pelvic-crest biopsies during long-term fluoride treatment of osteoporosis (author's transl)].

In 14 patients being treated with fluoride preparations for osteoporosis histomorphometric analysis of iliac biopsies showed that the volume of the mineralised spongiosa had increased by more than 20% above initial level in eight instances. The volume of the osteoid in ten cases had also increased, generally most markedly in the first year. In some cases the clinical symptoms corresponded to the histomorphometric findings. The results suggest that fluoride treatment of osteoporosis can be continued beyond one year. But this should only be done under precise control also of histological bone studies because in three of the patients the spongiosa volume had reached high normal values already after one to three years of treatment.

Adolescent↗

Conversion of T4 to T3 and rT3 and their cytoplasmic binding: pH dependency.

The fate of T4 in target organs is conversion to T3 which is mainly responsible for the nuclear action of thyroid hormones. To further investigate this converting step the increase of T3 and its analogue rT3 in rat liver microsomes was measured by specific radioimmunoassays after adding T4 to the incubation medium. Maximal increase of T3 occurred at pH 6.0 and of rT3 at pH 9.5 indicating that two different enzymic systems may be involved in the deiodination of the tyrosyl or the phenolic ring of T4. An increase in the binding capacity of cytosol proteins for T4, T3 and rT3 with rising pH demonstrates that there is also a pH dependency of the cytoplasmic binding of these iodothyronines. These reaction conditions should not only be considered in in vitro experiments, but may also be of importance in modifying the availability of T3 for its nuclear receptors.

Animals↗

[Pathophysiology and disgnosis of autonomous adenoma (author's transl)].

From personal experience in 200 patients and after a careful review of the literature autonomous adenoma of the thyroid is discussed under three aspects: 1. Different ways of its pathogenesis are possible. None of them has been sufficiently proven. 2. Differentiation by scintigraphy into a compensated, partially decompensated stage does not correlate sufficiently with the concentration of thyroid hormones in the blood and the overall clinical picture. The TRH test is negative in about 90% of patients independent of the stage evaluated by scintigraphy. 3. The diagnosis of the disease by modern tools is critically reviewed.

Adenoma↗

[Pathophysiology and diagnosis of autonomous adenoma (author's transl)].

From personal experience in 200 patients and after a careful review of the literature autonomous adenoma of the thyroid is discussed under three aspects: 1. Different ways of its pathogenesis are possible. None of them has been sufficiently proven. 2. Differentiation by scintigraphy into a compensated, partially decompensated and fully decompensated stage does not correlate sufficiently with the concentration of thyroid hormones in the blood and the overall clinical picture. The TRH test is negative in about 90% of patients independent of the stage evaluated by scintigraphy. 3. The diagnosis of the disease by modern tools is critically reviewed.

Adenoma↗

TBG-dependency of age related variations of thyroxine and triiodothyronine.

Thyroxine (T4), triiodothyronine (T3) and thyroxine-binding globulin (TBG) were determined in healthy individuals ranging in age from newborn to 95 years. T4: 10.25 +/- 1.62 microng/100 ml, T3: 1.62 +/- 0.35 ng/ml and TBG: 1.34 +/- 0.15 mg/100 ml, were found elevated until puberty compared to a middle age group with T4: 7.27 +/- 2.26 microng/100 ml, T3: 1.15 +/- 0.24 ng/ml and TBG: 0.98 +/- 14 mg/100 ml. T4 and T3 followed almost TBG concentration. In old age is dissociation between T4: 5.79 +/- 1.56 microng/100 ml, T3: 0.79 +/- 0.21 ng/ml and TBG: 1.28 +/- 0.15 mg/100 ml was found. Except for old age the ratio T4/TBG and T3/TBG minimized the age dependent variation of T4 and T3 and reduced the coefficient of variance from 26% to 17.7% for T4 and from 26.5 to 25% for T3. Age reduction of T4/TBG is 15% and of T3/TBG 13% respectively more pronounced than for T4 and T3 alone. These data indicate: 1) age related variations of T4 and T3 due to age dependency of TBG, 2) deviation of T4 and T3 values in old age from that expected by their TBG levels and 3) the importance of the routine use of hormone/TBG ratio.

Adolescent↗

Effect of dialysate calcium concentration on plasma parathyroid hormone during hemodialysis.

The effect of changes in the dialysate calcium concentration on calcium fractions and parathyroid hormone species in plasma during hemodialysis has been examined. C-terminal immunoreactive parathyroid hormone was suppressed when plasma calcium increased by greater than 25% whereas N-terminal fragments demonstrated an increase. The significance of this is discussed in light of present knowledge of parathyroid hormone metabolism.

Adult↗

[A highly sensitive C-terminal specific radioimmunoassay for human parathormone as a routine method (author's transl)].

The basis for the radioimmunoassay of parathormone (PTH) as a routine method is a new sheep antiserum and a labelled PTH stabilised by a modification of the purification technique. The antiserum is obtained by immunisation with pig and cattle parathormone, it is C-terminal specific and is used in the assay in a final dilution of 1:35000. The affinity to human PTH is markedly greater than of the antisera used up to now. Two purification steps of 125J labelled bovine PTH lead to a tracer with a nonspecific binding of approximately 5% which increases to approximately 10% within 6 weeks. All normal sera investigated so far were measurable quantitatively (normal range 0.7 to 2.5 mul/equiv.). The lower sensitivity range was at 0.3 mul/equiv. All patients with chronic renal insufficiency and dialysis patients have an increased PTH concentration (3.9 to greater than 20 mul/equiv.). This also applies to patients with primary hyperparathyroidism (2.9 to greater than 20 mul/equiv.).

Animals↗