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Biomedical subjects

M Titlbach

Publications and source records attributed to M Titlbach.

At least 19 recordsLinked to original sources
PubMed1998

Long-term action of potassium bromide on the rat thyroid gland.

Male rats fed by a standard diet with determined of bromine and iodine content were exposed to a 133-day oral administration of KBr (100, 200, 400 mg Br-/l drinking water). Their thyroid glands showed increased growth of the epithelial cells reflected by a microfollicular rearrangement of the parenchyma due to proliferation of very small follicles with a low or zero content of colloid. Morphometric analysis of thyroids of Br(-)-exposed animals revealed a significant decrease in the volume of intrafollicular colloid and marked increase in the number of the smallest follicles (areas up to 100 and 100-300 micron 2). In addition, the nuclei of thyrocytes showed an increased number of mitoses. The vascularization was increased as well. In the blood plasma of the Br(-)-exposed animals the T4 concentration was significantly decreased in dependence on the bromine concentrations. Thyroglobulin immunoreactivity in the colloid of Br(-)-exposed animals decreased after administration of 400 mg Br-/l drinking water. Increasing concentrations of Br- in the drinking water caused an increased bromine concentration in the thyroid, a decreased iodine content and a decreased I/Br molar ratio. The changes in the rat thyroid caused by long-term administration of 100 mg Br-/l were similar to hyperplastic parenchymal goitre and were comparable to those induced in previous experiments by the same bromine concentration administered over a 16- and 66-day period respectively.

Administration, Oral↗
PubMed1997

Expression of the proliferating cell nuclear antigen (PCNA) in the rat thyroid gland after exposure to bromide.

Analysis of expression of the proliferating cell nuclear antigen (PCNA) was used to determine the presumed hyperplastic character of morphological changes in the rat thyroid evoked by bromide administration. Male rats fed by a standard diet with determined iodine and bromine content were given potassium bromide. Control animals received no bromide. Experimental animals were given 10, 50 or 100 mg Br- per 11 drinking water for 16 and 66 days, or 100, 200, 400 mg Br-/l drinking water for 133 days. The thyroids of treated animals showed activation of growth of the epithelial follicular component as well as diffuse and focal microfollicular rearrangement of the parenchyma with higher follicular cells accompanied by a decrease of the amount of colloid even at low bromine concentrations (10-100 mg Br-/l drinking water). Using the PCNA-LI index (PCNA-positive nuclei.100/total number of follicular cell nuclei in the section), immunohistochemical analysis of PCNA in the nuclei of the follicular cells was carried out in parrafin sections. The index was significantly higher in bromide exposed animals (P < 0.01) and correlated well with the histological changes, with bromide concentration and with a increased mitotic activity of the follicular cells. PCNA analysis showed that morphological changes resembling a parenchymatic goitre reflect a microfollicular rearrangement of the thyroid of rats exposed to bromide and have the character of hyperplasia owing to the increased mitotic activity of the follicular epithelium.

Animals↗
PubMed1997

Potassium bromide and the thyroid gland of the rat: morphology and immunohistochemistry, RIA and INAA analysis.

The increasing environmental concentration of bromine has resulted in attempts to obtain information on its possibly deleterious effect on humans, particularly on a major target organ of this halogen i.e. the thyroid gland. In order to establish the morphological and functional effects of bromine on the thyroid, we have performed experiments on male rats which, in addition to a standard diet with an estimated iodine/bromine content, were fed for periods of 16 and 66 days with the small quantities of bromide expected to be encountered in the environment (10, 50 and 100 mg of Br-/l in drinking water). This treatment induced growth of the follicular epithelial component and microfollicular tissue rearrangement, a reduction of intrafollicular colloid, an increase in the height of the follicular cells and the number of mitoses, and it enhanced vascularization. Image analysis revealed a significant reduction in the volume of colloid, despite the accompanying rise in the number of minute follicles. The immunohistochemical positivity of the thyroglobulin fell in the microfollicular colloid of the exposed animals, although this was affected to a lesser extent in the larger follicles. The concentration of bromine in the thyroid increased with the amount of bromine intake, while at the same time the molar ratio of iodine/bromine decreased. The plasma level of T4 was lowered after both 16 and 66 days of treatment, but the T3 level only after 66 days treatment. The level of TSH did not exhibit any significant change. The observed changes, which have a parenchymatous goitre-like character, may have a direct relevance for human medicine, since the concentrations of bromide chosen in these experiments are readily encountered in the environment.

Animals↗
PubMed1994

Histophysiology of the obesity-diabetes syndrome in sand rats.

Insulin, glucagon, somatostatin, and PP cells were found by immunotopochemical and electron-optical techniques in the islets of Langerhans of the sand rat, proving that the islets in this species also contain the four basic cell types known to be found in the islets in mammals in general. The ratio of A cells to B cells was 1:4 (19.1% A cells to 80.9% B cells). The pancreas of the sand rat contained assemblages of various numbers of neurons in the intralobal and interlobular connective tissue. They did not seem related in any regular fashion to specific blood vessels or branches of the pancreatic ducts. No bundles of nerve fibers were found by either light or electron microscopy. Nonmyelinated nerve fibers were detected by electron microscopy in the stroma of the islets. In the sand rat the neuroinsular complexes are formed by the penetration of single nerve cells into the pancreatic islets. In the NH or long-term group the islets exhibited signs of stimulation. The number of islets was higher than normal (polynesia), with the islets themselves enlarged (macronesia). Double islets in the secretory ducts of the exocrine pancreas were frequent. The increase in islet size was due to hyperplasia of the B cells. The numbers of beta-granules in the B cells varied considerably. Glycogen was demonstrated in some islets. The fusion of beta-granules was shown in electron microscopic pictures. The electron-opaque centers of these granules were brighter than the others and appeared to have partly dissolved. The organelles of the B cells (ER, Golgi apparatus, and mitochondria) were well developed, this also being a sign of cell stimulation. No changes were observed in the B and PP cells. Stimulation of the islet cells was even more pronounced in the diabetic group. Due to hyperplasia, the islets in this group were significantly larger not only than those in the control group, but also than those in the NH group. The pancreata of this group of sand rats contained numerous small islets. Although necrotic B cells were found in the large islets of the pancreas, none were discovered in the small islets. The small islets were considered to be "regenerated" islets. Granulation was slight in the remaining functioning B cells. The hypophyses of the control group contained the GH, LTH, FSH, LH, and TSH cell types typical of this organ in other species. In the sand rat the granules of these cell types are of about the same size as has been stated for other rodents.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1993

Morphological changes after duct ligation of rabbit pancreas.

The morphological changes in rabbit pancreases after duct ligation were studied. These changes do not occur synchronically within the whole pancreas. The most advanced are those in the head portion; in the tail, their development is delayed. Pancreas duct ligation results in the pancreas edema, a gradual disappearance of zymogenous cells, replacement of acini by small ducts, an occasional differentiation of new zymogenous cells that quickly extinct again, and with the occurrence of amorphous or even fibrillary masses in the cytoplasm of duct cells to their further reduction. These changes are accompanied by the formation of loose connective tissue which gradually fibrotizes. The islets of Langerhans also undergo changes. In the tubules, a differentiation appears of their cells into endocrine elements. The existing islets get destroyed by both the fibrotic tissue and the formation of cavities in large islets with a consequent break-up of those islets. Both these destructive processes, in connection with the new formation, result in the appearance of small islets on the surface of which there is a capillary network. The cells of those islets are not of a fetal character.

Animals↗
PubMed1993

Experimental thyroiditis in guinea pigs and rabbits. Immunization with thyroglobulin and bovine thyroid gland suspension.

Morphological changes in the thyroid glands of the guinea pigs with autoimmune thyroiditis (EAT) experimentally induced by thyroglobulin (TGL) or immunization by the suspension of thyroid gland cells with CFA manifested mainly by atrophy and alterations of follicular cells, fibrotic tissue changes, formation of inflammatory lymphoplasmocytic infiltrations, multiplication of C-cells and by the increase in the proportion of lymphocytes with activated nucleoli in the tissue. The antigenic effects of TGL differed from those of the cell suspension; the effects of TGL participated especially in the formation of the infiltrates, the effects of cell suspension participated in the diapedesis of mononuclears and in the multiplication of C-cells. The findings correspond to the principal findings in human autoimmune lymphocytic thyroiditis. In an electron microscope, strongly dilated cisterns of endoplasmic reticulum (ER) and multiplied mitochondria in the cytoplasm of altered follicular cells were found. The wall of the follicles exhibited fully intact or altered C-cells. The latter had a large number of granules in cytoplasm with an unusually clear medullary substance. In the rabbit thyroid glands no morphological changes were observed following the immunization with both antigens. TGL antibodies examined immunohistochemically in the sera were present in all the sera of guinea pigs immunized with TGL and CFA. The antibodies determined by dot immunodetection were present in the sera of all guinea pigs immunized with TGL+CFA, the titres reached the level of 1:81 to 1:729; the highest titres were observed in the guinea pigs following the immunization by dose of 7.7 mg/kg after 12 weeks of immunization.

Animals↗
PubMed1991

Insulin immunization of guinea-pigs: biochemical, immunohistochemical and morphometric findings with and without the use of adjuvant.

Changes in the blood glucose level, glucose (GTT) and insulin (ITT) tolerance tests, anti-insulin antibody production and morphological changes in pancreatic tissues (in particular the islets of Langerhans) were studied. After immunization by insulin (I) or insulin combined with an adjuvant (IE, IF), the blood glucose level rose, changes were observed in the GTT and ITT and after four successive immunizations the immunofluorescence technique also demonstrated anti-insulin antibodies. None of the above changes was observed in the controls, to which saline containing complete Freund adjuvant (SF) or Listeria factor (SE) was administered. On the other hand, the morphological picture changed in both the experimental (IE, IF) and control (SE, SF) groups, in which (round) cell infiltration of the fine connective tissue of the omentum and even of mesentery, with nonspecific granuloma formation was observed, while huge multinuclear cells appeared in the SF group. The changes were more frequent in the IE and IF groups. The volume density of the pancreatic endocrine tissue increased significantly only in the experimental groups (I, IE, IF), in which the increase was accompanied, to a varying degrees, by degranulation of the B-cells. The results of analysis of volume density changes of A-, B-, and D-cell populations were correlated with the blood glucose levels. The morphological findings may explain why the originally insignificant production of anti-insulin antibodies and the increase in the blood glucose level observed in guinea pigs after the repeated administration of chromatographically purified insulin are significantly enhanced by the administration of adjuvants together with the immunizing agent. Complete Freund adjuvant was found to be more effective than the Ei Listeria factor.

Adjuvants, Immunologic↗
PubMed1990

Morphological changes in the human thyroid gland cultivated in continual flow system.

In the present pilot study, the human thyroid gland tissue was cultivated under continuous culture conditions in the culture chambers of the ACUSYST-S system to determine morphological changes as well as the secretion of thyreoglobulin (Tgl) and thyroid hormones. After 24 hours of cultivation the follicular structure of the tissue was preserved in peripheral parts only, and there were regressive changes in the epithelium center. After 72 hours the regressive changes appeared in isolated follicles only; the size of the follicles increased, the height of the follicular epithelium decreased and there were macrophages present with phagocytized cell debris. After 144 hours disintegration of epithelia took place in the centre, while at the periphery the original follicles survived and very tiny new follicles formed, consisting of only 6 to 8 cells each and surrounding in section the homogeneous colloid. The parenchyma picture suggests a possibility of functional regeneration as an expression of adaptation to the conditions newly arisen during cultivation in a culture chamber. There was no significant influencing of the thyroid hormone secretion during cultivation. On the other hand, the Tgl secretion decreased throughout cultivation.

Culture Media↗
PubMed1989

Immunohistochemical, morphometric, and ultrastructural investigations of the early development of insulin, somatostatin, glucagon, and PP cells in foetal human pancreas.

Fresh autopsy specimens of pancreas, taken from 18 human foetuses at the 10th (n = 4), 12th (n = 7), and 14th (n = 7) weeks of gestation, were analyzed immunohistochemically for the presence of islet parenchymal cells, immunoreactive with antisera raised against insulin (B cells), somatostatin (D cells), glucagon (A cells), and pancreatic polypeptide (PP cells). All four islet cell types were found sporadically within or near the epithelium of the small excretory ducts at the 10th week of development. At the 12th week, their presence appeared to be no longer restricted to the duct epithelium, as some B cells were found also in small clusters outside the ducts. At the 14th week of development, the B cells formed large clusters in the neighborhood of the excretory ducts. It is at this stage that the first parenchymal cells with Grimelius argyrophilia could be found. They were supposed to represent A cells. The B cells were found to be the predominating type of islet cells (about 50%) at the 10th week of gestation. The relative volume density was about 25% for the D cells, about 15% for the A cells, and about 10% for the PP cells. At the 12th and 14th weeks of development, the relative numbers of B and PP cells decreased somewhat (to 36 and 6%, respectively), whereas those of the D and A cells were found to increase (to 30 and 27%, respectively). The relative volume density of the total islet parenchyma was about 2, 6, and 21% at the 10th, 12th, and 14th weeks of development, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryonic and Fetal Development↗
PubMed1988

Immunodiabetes in rabbits.

The changes of basal glycemia and of that during the glucose and insulin tolerance tests as well as of the production of hemagglutinating antibodies in rabbits immunized with crystalline insulin (CI), chromatographically purified insulin (CPI) and waste products of the chromatographic purification of insulin (WP), both with and without complete Freund's adjuvant (CFA) were studied. Following immunization with CI and its components the glycemia increased characteristically and the course of glucose and insulin tolerance tests was changed. The peak levels of antibodies were found following immunization with WP, while the lowest ones appeared following the application of CPI. Following the immunization with a mixture of antigens with CFA higher levels of antibodies were usually observed than following the administration of antigens without adjuvant. No association was found between the titers of antibodies and glycemia values. The principal morphological change in immunized animals was found to be a partial degranulation of B-cells, often accompanied by hyperplasia of A-cells. In groups immunized with CI or CPI mixed with CFA we detected even insulitis, which was absent in the other groups. Following immunization with CI mixed with CFA such cells were found whose granules in the ultrastructure showed conspicuous similarity to those of foetal (immature) rabbit B-cells. It was assumed that in insulin immunized rabbits the initial damage of islets was followed, at least in some regions, by reparative processes. This was indicated by the findings of mitosis figures in B-cells as well as by the islet A-cell hyperplasia.

Animals↗
PubMed1987

Prenatal development of the cat thyroid: immunohistochemical demonstration of calcitonin in the "C" cells.

The presence of calcitonin in the cat thyroid was studied immunohistochemically in a series of gland development. The first positive cells are to be found on the 38th day of gestation, i.e. 1-2 days after level nine of ontogenetic development has been reached. The cytoplasm of these cells form only a narrow border round the nucleus. With advancing development the number of calcitonin-positive cells rises, the cytoplasm becomes intensely positive and its amount increases. From approximately the 50th day of prenatal development, the initially diffusely scattered, solitary calcitonin-positive cells are gradually replaced by groups of cells, which begin to occupy a characteristic position in relation to the follicular epithelium. The largest quantity of calcitonin-positive cells is found in foetuses about to be born. In non-pregnant adult cats, the incidence of immunohistochemically calcitonin-reactive cells is more sporadic and their distribution in the lobes of the thyroid is uneven.

Animals↗
PubMed1987

Neuroendocrine background of the pathology of the islets of Langerhans. A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit.

As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.

Animals↗
PubMed1987

Ontogeny of the pancreatic islet parenchymal cells in the rabbit--an immunohistochemical and ultrastructural study with particular regard to the earliest appearance of argyrophil insulin-immunoreactive cells.

Six early developmental stages of the rabbit pancreas were selected, viz. the embryonic ages 10 days 10 hours, 10 days 18 hours, 11 days 14 hours, 13 days, 15 days, and 18 days. Both non-immunological (histologic-tinctorial features, including argyrophilia, and transmission electron microscopy) and immunohistochemical (the indirect immunofluorescence and/or the peroxidase-anti-peroxidase procedure) methods were used to follow the time-course for the appearance and differentiation of both endocrine (islet) cells and exocrine acinar epithelium. The immunological procedures were, however, limited to the 3 later developmental stages. In the first 3 developmental stages only the dorsal anlage of the pancreas could be found. It was just investigated ultrastructurally. Then, a few parenchymal cells were observed, equipped with secretory granules of endocrine type, indicating that an early differentiation of islet cells had already begun. In the later 3 developmental stages a ventral pancreas anlage was present and at least 2 types of argyrophil islet cells, equipped with secretory granules, were observed. In the pancreas anlage of 13-day-old embryos these early endocrine cells were found to be glucagon-immunoreactive. At the developmental age of 15 days argyrophil insulin-immunoreactive cells were also present, and in the 18-day-old embryos a few somatostatin cells could occasionally be discovered, too. No PP cells were found. Any exocrine acinar differentiation (with zymogen granules) was not observed until at the developmental age of 18 days.

Aging↗
PubMed1985

Postnatal maturation of the islets of Langerhans in sheep. Light microscopic, immunohistochemical, morphometric, and ultrastructural investigations with particular reference to the transient appearance of argyrophil insulin immunoreactive cells.

The endocrine pancreas of lambs was found to offer an interesting animal model for some aspects of normal and pathological postnatal maturation of the islet parenchyma also in man. Normal features in lambs, previously observed in man, were the high volume density (5-8%) of the islet parenchyma, the high incidence of D (somatostatin) cells (about 30% even in young adult sheep), and the concentration of PP cells to the posterior part of the head of the pancreas. Particularly interesting was the presence in newborn lambs of large islet bodies (0.2-2 mm in diameter), consisting (to more than 90%) of large, argyrophil (Grimelius), granulated, parenchymal cells which were found to be insulin immunoreactive. Their secretion granules were smaller and more electron dense than those of the mature non-argyrophil B (insulin) cells. The argyrophil insulin immunoreactive cells often formed intercellular cavities and they could be equipped with microvilli and even cilia. At birth, these large islet bodies constituted more than half of the total islet parenchyma, but already during the first 10 days they underwent marked regressive changes (i.e. with large haemorrhages; "Blutinseln"); in 2-month-old lambs and in young adult sheep they had practically disappeared. These argyrophil insulin immunoreactive islet cells were considered to represent immature B cells with some persisting foetal characters. In 1- and 4-day-old lambs some non-argyrophil B cells in small islets of Langerhans harboured secretion granules of both types of B cells, indicating that a transformation could occur from 1 type to the other in this dual population of islet B cells. It was speculated that the argyrophil insulin immunoreactive cells could be homologues to the argyrophil islet cells often occurring in insulin-producing islet-cell neoplasms and in nesidiodysplasia in man.

Animals↗