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Biomedical subjects

A Zink

Publications and source records attributed to A Zink.

88 records · Page 5Linked to original sources

Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6-23 cells: possible involvement of a pertussis toxin-sensitive G-protein.

The mechanisms by which somatostatin inhibits hormone release are complex and involve, among other things, reduction of both intracellular cAMP and intracellular calcium. We studied the influence of the long-acting somatostatin analogue octreotide on norepinephrine (NE)-induced changes in intracellular calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell line, rMTC 6-23. Increases in the extracellular calcium concentration ([Ca2+]e) induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also could be blocked by the addition of EGTA or verapamil. Octreotide prevented or reversed the NE-induced increase in [Ca2+]i. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+]e, most probably through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated rise in [Ca2+]i by a pertussis toxin-sensitive G-protein, most probably through a direct effect on NE-activated calcium channels.

Animals↗

Measurement of free cytosolic calcium in single cells: method and application.

Intracellular calcium [Ca2+]i acts as an important intracellular messenger system for secretion and synthesis, cell growth and differentiation. In order to demonstrate definitively that a change in [Ca2+]i is responsible for a physiological event, one has to measure [Ca2+]i directly within intact cells and correlate the time course of any [Ca2+]i changes with the biological response. Measurement of [Ca2+]i was done in a single cell preloaded with fluorescent Ca indicator fura2 using a fluorescent unit (lonoquant) consisting of an inverted microscope (Zeiss IM 35) equipped with a mercury lamp and a rotating filter wheel containing filters at wavelengths of 340 and 380 nm. Cells were alternately excited and emission signals of fura 2-loaded cells were collected by a photomultiplier and recorded on-line on a computer screen. As a model system, the rat C-cell carcinoma cell line rMTC 6-23 secreting calcitonin was used. An acute elevation of extracellular calcium resulted in an increase in [Ca2+]i within 5 sec and rapid release of preformed calcitonin. This tight linkage between extracellular calcium and [Ca2+]i is mediated via Ca influx through voltage-dependent Ca channels. These channels are modulated by intracellular cAMP, yielding a rhythmic oscillation of [Ca2+]i, as well as by extracellular somatostatin blocking the Ca channel and the increase of [Ca2+]i via a pertussis toxin sensitive Gi protein. The change in [Ca2+]i is associated with changes in calcitonin secretion, confirming the stimulus secretion coupling via voltage-dependent Ca channels in C-cells.

Animals↗

Somatostatin acts via a pertussis toxin-sensitive mechanism on calcitonin secretion in C-cells.

The effect of the somatostatin analog octreotide on cAMP-mediated calcitonin (CT) secretion and cAMP accumulation in C-cells was investigated. Glucagon stimulated cAMP accumulation and CT secretion with a maximal effect at a concentration of 10(-6) M. The cAMP antagonist RpcAMPs blocked the glucagon-induced CT secretion down to control levels. Therefore, no other second messengers seem to be involved in glucagon-stimulated CT secretion. Octreotide in increasing doses (10(-9) to 10(-6) M) inhibited cAMP accumulation and CT secretion with a maximal effect at a concentration of 10(-7) (40% and 29% of control values, respectively). Pretreatment of the cells with 100 ng/mL pertussis toxin for 24 hours abolished the inhibitory effect of octreotide on cAMP accumulation and CT secretion (82% and 58% of control values, respectively). Similar results were obtained under the influence of the phosphodiesterase inhibitor IBMX. Therefore, we conclude that somatostatin modulates adenylate cyclase-coupled CT secretion in C-cells via a pertussis toxin-sensitive G-protein possibly in an autocrine/paracrine way.

Adenylate Cyclase Toxin↗

Papillary carcinoma in an ectopic thyroid.

Ectopic thyroid tissue can be seen anywhere from the foramen caecum to the lower neck. Most frequently it presents as a thyroglossal duct cyst associated with a normal thyroid gland. Less common is total ectopia, which can occur as a lingual thyroid or occasionally in non-lingual locations. Malignant transformation of such ectopic tissue is extremely uncommon. Only 21 cases of lingual thyroid carcinomas have been reported until 1971. We present, to our knowledge, the first case of a papillary carcinoma in a non-lingual ectopic thyroid in the absence of an orthotopic thyroid.

Adolescent↗

Down-regulation of calcitonin receptors in T47D cells by internalization of calcitonin-receptor complexes.

T47D cells possess specific calcitonin (CT) receptors and a CT-responsive adenylate cyclase. Internalization of part of their CT receptors has been suggested. At 37 degrees C, bound 125I-labelled salmon CT (sCT) becomes increasingly resistant to acid washing, which can remove surface-bound hormone, thus indicating internalization. Monensin and chloroquine, which raise the pH of the lysosomes and thereby inhibit cellular processing of endosomes, inhibit the decrease of total bound activity seen in the controls. Acid-resistant (internalized) activity increases to the levels of total binding. Preincubation with sCT leads to a loss of specific binding. Recovery of CT binding is prevented by monensin, which also inhibits transport of cellular proteins to the cell membrane. Recovery is not influenced by chloroquine. As chloroquine prevents recycling, we conclude that after binding of CT the receptors are internalized, transferred to a lysosomal compartment, and degraded intracellularly without recycling. All receptors seem to undergo internalization. Desensitization to CT in T47D cells is at least partly mediated by intracellular metabolism of CT receptors.

Chloroquine↗

Action of calcitonin gene-related peptide at the calcitonin receptor of the T47D cell line.

Some effects of calcitonin (CT) can also be produced by calcitonin gene-related peptide (CGRP), an alternative product of the calcitonin gene. This might be mediated by interaction of CGRP at the CT-receptor site. The human breast cancer cell line T47D possesses well characterized CT-receptors (KD = 2.3 x 10(-10) M for 125I salmon CT). 50% inhibition of 125I-sCT binding was achieved with 10(-9) M sCT, 5 x 10(-6) M rat CGRP and 10(-5) M human CGRP. Half maximal cAMP production in T47D cells was seen with 6 x 10(-10) M sCT, 5 x 10(-6) M rCGRP and 10(-5) M hCGRP. Binding and displacement capacity as well as the biological activity of CT and CGRP seems to correlate well. These findings suggest that CGRP in pharmacological doses acts via the CT-receptor. This could be explained by the homology and conformational similarities between CT and CGRP.

Breast Neoplasms↗

Childhood poisoning in a paediatric hospital: the Luebeck experience.

1 Case documentations in Poison Control Centres represent today probably the most useful source of information on actual trends. They are generally restricted to toxicologically relevant information, but they do not describe true incidence patterns. Population based analyses of incidence therefore generally consist of retrospective studies of hospital data. The regional and historical limitations of such studies restrict their usefulness in prevention and intervention. A solution could be prospective studies in defined regions. 2 Such a prospective registration of poisoning in children was started in 1982 in the Luebeck Medical School's Paediatric Hospital. This hospital is the only institution treating acute poisoning in the region, so that regional representation of the data can be expected. Based on the experiences of a previous retrospective analysis of 730 poisoning cases treated between 1976 and 1980, a documentation form was developed for the registration of clinically and epidemiologically relevant data. Information on the toxic substance and the poisoned child is complemented by data on the clinical treatment as well as on socio-demographic parameters. 3 The first months' experience with the documentation form, and the results of the registration of 95 cases are presented. Possibilities and limitations of such registration systems are discussed.

Child↗

[Epidemiological and socio-psychological aspects of accidents in childhood (author's transl)].

The present study is based on the assumption that accidents in childhood may be interpreted as a possible result of conflicts between the children and their social environment. Questioning of 100 children who had suffered from accidents, and of their parents showed that children having incomplete families were largely overrepresented in the study group. They also had already experienced a greater number of prior accidents. Their child-development was less favourable, more parents reported unusual behavior and possible psychosomatic symptoms. The social situation of the single-parents' families was characterized by difficult economic conditions. These families mainly belonged to lower social classes. The results underline the necessity not only to consider medical (therapeutic and rehabilitating) measures but also soci-pedagogical or socio-therapeutic support.

Accidents↗

Malignant tumors in an ancient Egyptian population.

Since it is still an open debate whether malignant tumors are mainly influenced by environmental factors, the frequency of such malignant tumors in historic populations with different living conditions is of particular interest. In the present study, we investigated the occurrence of malignant tumors affecting bone tissue in a population of mumrnies and skeletons, which had been excavated from the large necropolis of Thebes-West, Upper Egypt. Our study material comprised a series of at least 415 individuals (thereof 325 adults) dating from approx. 1500-500 B.C. All individuals had been mummified, but were severely damaged and partially broken by grave robbers, so that often only parts of the mummies/skeletons were available for investigation. The available specimens were subjected to careful macroscopic examination, while isolated findings were radiologically analyzed. Using this approach, we identified at least 4 cases showing malignant tumors affecting the skeleton. In two cases, multiple mixed osteolytic-osteoblastic lesions suggested multiple metastases from carcinomas. Two further individuals presented with multiple osteolyses (vertebra, pelvis, skull) most suggestive of multiple myeloma. The observation of at least 4 cases of malignant tumors with osseous manifestation in a series of 325 adult individuals provides clear evidence that malignant tumors were not a rare event in the ancient Egyptian study population, particularly when the limitations of a study of tumors manifested only in osseous remnants are taken into consideration. A calculation of the age- and sex-adjusted tumor frequency in our material in comparison with a recent model for such a material by Waldron (1996) indicates that the rate of malignant tumors with bone affection in our series is higher than in an English population from 1901-1905, although lower than in a comparable present day population. This clearly indicates that important factors affecting malignant tumors were effective even in historic populations.

Adult↗

[Epidemiology of rheumatic diseases in the German Federal Republic-- current state and perspectives].

During the last few years epidemiologic research on rheumatic diseases in the Federal Republic of Germany has been sponsored, primarily, by the Ministry of Research and Technology. The projects, either completed, ongoing or planned, concentrate on health services research, population studies of the prevalence of specific diseases or complaints (rheumatoid arthritis, back pain, juvenile chronic arthritis, osteoarthritis) and clinical epidemiology, especially concerning early arthritis. As a result of the general shortage of public funds, less projects could be sponsored than expected. The aim of the Ministry to establish research organizations that will continue to exist even if public funding is curtailed seems to be jeopardized. Therefore, not only the federal government, but also the federal states and institutions like the Deutsche Forschungsgemeinschaft should be engaged in this field. More groups should have the opportunity to work in epidemiology of rheumatic diseases, and groups which are able to work in close connection with basic scientists and rheumatological clinicians should be institutionally affiliated on a permanent basis. This is critical for the further development of this discipline which is important for health services research, quality assurance, as well as for analytical research and prevention.

Cross-Sectional Studies↗

[Epidemiology of rheumatologic health care in Germany].

Within the governmental funding program of rheumatological centers a uniform patient registration is performed. It provides information of the proportion of patients with inflammatory rheumatic diseases who are seen in specialized care, how early they are seen and which forms of treatment are provided. In 1993 in the 20 participating centers almost 26,000 patients have been recorded. The centers only reach a small proportion of the true prevalence but they see their patients early in the disease: 60% of the patients have been seen within the first year. Deficits exist in the areas of ergotherapy, psychological support and patient education. One reason for the small proportion of people with the diseases who are seen in specialized care is the lack of rheumatologists in outpatient care. More rheumatologists in private practices as well as the participation of clinical rheumatologists in outpatient care including reasonable forms of payment are needed.

Arthritis, Rheumatoid↗

[Management of rheumatoid patients by rheumatologists in a large metropolitan area].

Five outpatients clinics and four private practices in Berlin have participated in a uniform outpatient register in 1992. This documentation has been used since 1993 in all of the 21 rheumacenters funded by the Federal Minister of Health. It gives information on diagnoses, ways of admission, therapies, complaints as well as functional and socioeconomic status of the patients. Data of about 3000 patients pertaining to earliness of admission, therapies, work disability, and correlations of education and prognosis of R.A. are reported.

Activities of Daily Living↗