Regional anaesthesia.
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Anesthesia, Conduction↗
Biomedical subjects
H Gerber
Publications and source records attributed to H Gerber.
[Histopathogenesis of goiters].
The basic mechanisms acting in the transformation of a normal thyroid gland into a toxic or nontoxic goiter are summarized: 1) Any goiter arises from multiplication of follicular epithelial cells forming new follicles. 2) In the follicular epithelium there are cell families with much higher than average growth potential. 3) Cells of an individual follicle are not identical but heterogeneous. 4) Each follicular cell has a certain level of autonomy of growth and of function.
Cell Division↗
Pathogenesis of nodular goiter and its implications for surgical management.
Despite sufficient iodine supply, goiter continues to be of considerable surgical significance in formerly endemic countries. It now appears that iodine deficiency and increased thyrotropin stimulation are not the only causes of goiter. Xenotransplantation of human thyroid tissue onto nude mice allowed study of the regulation of growth and function in human goiter tissue. Grafts of human thyroid tissue growing in nude mice could be shown to react to endogenous mouse thyrotropic stimulation and suppression. 131I autoradiographs of xenotransplanted goiter tissue showed as marked a heterogeneity as did the original goitrous tissue prior to transplantation. There was no firm correlation between the morphologic appearance of a follicle and its iodine metabolism. Scintigraphically "cold" and "hot" goiter tissue differed from each other quantitatively but not qualitatively; i.e., both "hot" and "cold" tissue were composed of metabolically active and nonactive follicles. Iodine organification was not completely suppressible by thyroxine treatment; this indicates autonomous functional activity. The distribution of proliferating tissue labeled by 3-H-thymidine did not parallel the distribution of functionally active tissue labelled by 131I. Thyroxine treatment did not completely inhibit 3-H-thymidine incorporation, indicating autonomous growth. Thus, our pathogenetic concept of goiter formation is based on three mainstays: (1) goiter heterogeneity, (2) autonomy of growth and function, and (3) dissociation of growth and function in human goiter tissue. Thus, the surgeon dealing with goiter ought to remove all pathologically altered tissue, i.e., nodular tissue, irrespective of its appearance on scintiscans.
Animals↗
[The treatment of equine sarcoidosis by carbon dioxide laser].
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Animals↗
[Evaluation of the results of performance tests for stallions and the Swiss saddle horse shows].
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Analysis of Variance↗
[Current TSH-sensitive assays simplify thyroid diagnosis].
The methodology and clinical application of sensitive TSH assays are discussed. The new immunometric assays not only distinguish between normal and elevated, but also between normal and suppressed TSH values. Therefore, after clinical examination of the patient, serum TSH measurement by a sensitive assay may be used as a first line test whenever hypo- or hyperthyroidism is suspected. Normal TSH indicates euthyroidism and obviates the need for further thyroid function testing. In patients with elevated or suppressed TSH values, free T4 and (if TSH is suppressed and free T4 normal) free T3 are measured to discriminate between overt and subclinical hypo- or hyperthyroidism. Testing with TRH continues to be useful in some more complex cases, when the above-mentioned tests are not conclusive.
Diagnosis, Differential↗
Naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of mouse thyroids.
The proliferation pattern of some scattered clones of naturally occurring follicular cells with an exceedingly high intrinsic growth potential was investigated in the mouse thyroid gland. In particular, evidence was sought to demonstrate that the high propensity to replicate is a stable trait transmitted from the progenitor cells to their offspring. We hypothesize that these cell clones are at the origin of the multiple adenomas that invariably arise in chronically stimulated thyroid. Growth stimulation was induced either by hemithyroidectomy or by methimazole feeding. In a first series of experiments, involving hemithyroidectomized animals, [3H]thymidine was administered continuously for 3 weeks by means of osmotic minipumps, so that all cells entering the mitotic cycle during that time were labeled. Hemithyroidectomy led to a 3-fold increase of the fraction of labeled cells in the remaining lobe. The increase was prevented by thyroxine treatment in thyroid-stimulating hormone-suppressing doses. Autoradiographs of contiguous serial sections across whole follicles showed that roughly 75% of the labeled cells were clustered in groups of 3 or more, rather than being randomly distributed. In a second set of experiments, glands stimulated by methimazole-induced thyroid-stimulating hormone hypersecretion were pulse-labeled by a single i.p. injection of [3H]thymidine. Animals were sacrificed either 2 h or 3 weeks after the administration of the label. The thyroids were excised and the fate of labeled thyroid cells was analyzed autoradiographically. In the 2-h exposure, about 95% of all labeled follicular cells were single and the remaining 5% were in pairs. In contrast, about 50% of all labeled cells were clustered in groups of 3 to 12 cells 3 weeks after the pulse labeling. The number of silver grains per nucleus was compared to that of the identically exposed controls. The intensity of label per cell appeared to be decreased in proportion to the size of the labeled clusters, indicating that clusters had generated several subsequent generations of cells. The results support previously produced evidence that highly growth-prone cells naturally occur within the normal thyroid and demonstrate, in addition, that their high intrinsic growth rate is a stable, inheritable trait. Cells which replicate at a rate faster than that of the average epithelial cell have a tendency to overgrow during goitrogenesis. They may be at the very origin of the nodules and adenomas commonly found in experimentally produced and naturally occurring goiters.
Animals↗
Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.
Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.
Animals↗
Progressive recruitment of follicular cells with graded secretory responsiveness during stimulation of the thyroid gland by thyrotropin.
One of the earliest responses of the thyroid cells to TSH is macropinocytosis with formation of intracellular colloid droplets. We demonstrate here that increasing stimulation with TSH not only elicits a highly individual macropinocytotic response among different follicular cells but that the fraction of TSH-responsive cells is also a function of the TSH dose. After pretreatment with T4, mice and rats were injected ip with bovine TSH and killed 2 h later. The macropinocytotic response to TSH was evaluated on periodic acid-Schiff-stained 3-microns sections of the thyroids in terms of droplet number per 25 follicles and, in addition, by assessing recruitment, i.e. percentage of droplet-containing cells. Both variables increased with increasing TSH stimulation until they reached a plateau at about 9 mU TSH in mice and at about 300 mU TSH in rats: the percentage of droplet-containing cells gradually increased in mice from 2% (no TSH) to 67% (9 mU TSH) and in rats from 11% (no TSH) to 54% (300 mU TSH). Overall pinocytotic response as well as thyrocyte recruitment could be modified by extra- and intrathyroidal factors: for example, pretreatment of the mice with an iodine-deficient diet increased the maximal percentage of droplet containing cells to nearly 90%. Obviously, two separate components of the macropinocytotic response of the thyroid gland to TSH can be distinguished: the first is the gradually increasing fraction of droplet-containing cells, the second is the well known increase of the number of colloid droplets in each TSH-responsive cell with progressive TSH stimulation. Recruitment of thyrocytes with a gradually increasing natural threshold to a hormonal stimulus appears to be a fundamental mechanism in the thyroid gland and possibly in other organs.
Animals↗
Age-related failure of endocytosis may be the pathogenetic mechanism responsible for "cold" follicle formation in the aging mouse thyroid.
With advancing age, 60-80% of the follicles of the mouse thyroid gland turn "cold", i.e. they lose their normal capacity to iodinate thyroglobulin (Tgb). Cold follicles are morphologically characterized by their large size, by deeply periodic acid-Schiff-stained colloid and by flat epithelial cells. We investigated the hypothesis that a progressive, age-related failure of endocytosis, leading to a gradually increasing mismatch between production of new Tgb and resorption of stored Tgb, could lead to overfilling of colloid stores with consecutive impediment of diffusion. To this purpose, labeling of the thyroids was started when mice were 3 months old, and 125I was continuously administered thereafter for 2-6 months. After this time, all follicles were homogeneously labeled in autoradiographs. Tracer application was then discontinued. Autoradiographs obtained at intervals during the washout of the tracer yielded a mirror image of that observed after acute labeling. The large follicles which were cold after acute labeling in old animals now still retained labeled iodoproteins even after 7 weeks of washout, i.e. at a time when morphologically normal follicles had long lost their labeled Tgb stores. Thus, the cold follicles of the old thyroid must have been functioning normally during equilibration of young thyroids, but have then gradually lost their capacity to iodinate and to remove stored Tgb from the colloid. The observation supports the thesis that aging primarily affects the cytoskeleton and, thus, the cell's endocytotic machinery. This effect of aging on the thyroid can be prevented by life-long stimulation of the gland by TSH.
Aging↗
In vivo studies of pathogenic, immunogenic and protective properties of Roma strain rabies virus recovered from a persistently infected BHK21 cell line.
Rabies virus strain Roma was adapted to grow in BHK21 cells and a persistently infected cell line was established. The cell line released infectious virus only irregularly and at low titers. We report in this work experiments carried out in mice on pathogenicity, immunogenicity and protective properties of the virus recovered at different phases of the persistent infection. The adapted virus strain was only weakly pathogenic when injected intracerebrally and apathogenic when given intramuscularly. Dose-response curves in mice of virus produced by the persistently infected cell line were irregular, often with deaths occurring at low but not at high virus doses. Moreover, the symptoms of rabies differed from the course of disease induced by unadapted Roma strain rabies virus. Sera of survivors of a first non lethal inoculation were tested for the presence of rabies virus neutralizing antibodies and these mice were challenged with virulent CVS rabies virus. Animals having survived the highest viral doses had the highest antibody titers and resisted a challenge with the standard challenge virus.
Animals↗
[Malignant hyperthermia: clinical aspects, diagnosis and practical procedures].
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Anesthesia, General↗
Respiratory and circulatory influence on photopapillometry.
Respiratory and circulatory conditions that could have an influence on measurements of pallor of the papilla were evaluated with our photopapillometer in a controlled study on canines. The brightness of the papilla rim and the width of the arterioles emerging from the optic nerve head were measured in six anesthetized dogs under normal, hypertensive, and hypotensive circulatory conditions, as well as under various respiratory manipulations, and the parameters were compared for statistical correlation. Both brightness and vessel width remained constant for a wide range of arterial pressures when the rest of the experimental conditions were kept stable at naturally occurring levels. If respiration and circulation were brought to extreme levels, however, there was a statistical tendency for the brightness of the papilla to be dependent on arterial and pulmonary arterial blood pressure. The importance of these findings is discussed with regard to their influence on objective measurements of fundus brightness.
Animals↗
The effect of propranolol on whole-body microvibrations during examination stress.
Whole-body microvibrations (MV) in three dimensions were measured in 51 volunteers, all medical students, 26 without and 25 with beta-receptor blockade (propranolol), immediately before a practical physiology examination and during the ensuing vacation. Propranolol impeded the increase in MV values in all three axes, significantly those in the z axis (vertical), the differences in MV values between the two measurements being minimal in the beta-receptor blocked group. On the other hand, propranolol enhanced MV in the x axis (anteroposterior) and the y axis (transverse), the y axis difference being significant only in females. Propranolol obviously relieves examination stress: the majority of candidates (52%) felt "quieter" in the examination with than in other similar situations without beta-receptor blockade. Propranolol was, however, without effect on the examination results. The rectified impulse in the z axis when related to body weight (Jz) correlates linearly with the calculated cardiac output. Propranolol, however, reduced cardiac output more than Jz, pointing to a Jz component non-sensitive to beta-receptor blockade. The part played by muscle tonus, mainly reflected in the y axis, thus remains unknown. The large and slow oscillations in the x and y axes, observed particularly in beta-receptor blocked females, might be attributed to diminution in standing ability.
Adult↗
Iodination of thyroglobulin molecules depends on their diffusion velocity in follicular colloid.
We have studied in vitro the effects of altered physicochemical properties of thyroglobulin molecules in solution and of the solution itself on iodination kinetics and hormone synthesis. Any change in hydrodynamic properties had a far greater effect in compartmentalized systems, obtained by coating the test tubes with peroxidase, than in conventional homogeneously mixed systems. Increasing thyroglobulin concentration in a range still far below that existing in vivo greatly retarded iodination and hormone synthesis. In contrast, a number of physiological and non-physiological changes of thyroglobulin structure, such as desialylation, preiodination, oxidation and denaturation, strikingly accelerated iodination. The highly variable physical-chemical state of thyroglobulin molecules appears to be a main determinant of protein diffusion within the colloid and, thereby, of iodination kinetics and rate of hormone synthesis. Moreover, alterations of the physicochemical state of thyroglobulin molecules may explain some hitherto ill-understood diffusion phenomena in live follicles.
Chemical Phenomena↗
Equine leucocyte antigen system. IV. Recombination within the major histocompatibility complex (MHC).
A case of recombination between the putative class I ELA antigen series and the structure(s) governing mixed lymphocyte reactivity in an informative horse family is described. The results of serological typing, 'lysostripping' and mixed lymphocyte culture tests strongly suggest that the recombination took place between two loci and is not intragenic. An alloantigenic membrane structure, provisionally called B1, which does not belong to the known ELA series, was also involved in the cross-over. The B1 antigen resembles the class II gene products of other species in two respects: it is not present on platelets, and alloantiserum with specificity for B1 inhibits the stimulatory effect of B1-carrying cells in mixed lymphocyte cultures. The B1 antigen does not follow the classical distribution, however, being expressed on both B and T lymphocytes. The finding of separate loci for the first series of ELA antigens and the MLR governing structure(s) demonstrates the similarity of the genetic organization of the horse MHC to that in other species.
Animals↗
Treponemal serology and blood groups on Bali island, Indonesia.
As part of a multidisciplinary study of the population of Bali, Indonesia, 2452 blood samples from people of both sexes were tested for treponemal infection and blood groups. Analysis of blood groups of the 81 patients reactive to the Treponema pallidum immobilisation (TPI) test, who were considered to have latent or inactive yaws, compared with a control group of 552 healthy Balinese, showed that the ratio of MM to MN and NN phenotypes was 2.25 times higher in the patients than in the controls (chi 2(1) = 10.2, p less than 0.005). A speculative hypothesis is that yews infection gives people with the MM phenotype a lower selective fitness. This hypothesis could explain the low prevalence of the M gene in the Australo-Melanesian populations.
Humans↗
Diffusion of thyroglobulin in the follicular colloid. (Minireview).
Methods used for estimating in vivo diffusion velocity of thyroglobulin (Tgb), the factors affecting hydrodynamic properties of thyroidal colloid and the effects of changing diffusion properties on follicular function are briefly reviewed. The principal methods, besides pure in vitro techniques, are autoradiography of thyroid sections after in vivo labelling of Tgb and freezing autoradiography for examining colloidal diffusion of ions or other small molecules. The main factors known to affect diffusion of Tgb in the colloid space are concentration and actual physico-chemical properties of the Tgb molecule itself, the latter parameter depending on several factors such as sugar content, iodination degree, etc. Additional factors are thyrotropin which speeds up and drugs such as pentobarbital or verapamil which slow down the velocity of Tgb diffusion. High iodine supply has a retarding effect on Tgb diffusion in the colloid of mice thyroids. Any change of Tgb diffusion in the colloid may have a striking effect on follicular function. The hydrodynamic properties of the colloid components are increasingly recognized as a potentially important factor in regulating kinetics of hormone synthesis.
Animals↗