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H J Peter

Publications and source records attributed to H J Peter.

50 records · Page 3Linked to original sources
PubMed1983

[Autonomy and heterogeneity of the follicle in euthyroid and hyperthyroid human nodular goiter: answer to old riddles?].

The mechanisms responsible for the transformation of a morphologically and functionally normal thyroid into a heterogeneous eu- or hyperthyroid nodular goitre are summarized. The 3 basic processes of goitre pathogenesis are: 1. Each goitre develops from a normal thyroid gland by generation of new follicles. 2. New follicles are formed by multiplication of preferentially replicating cell clones of the follicular epithelium. Follicles already begin multiplying in response to a goitrogenic stimulus too weak to enhance metabolic functions other than replication. 3. The epithelial cells of normal follicles are not homogeneous and monoclonal, but belong to different populations with different metabolic equipment. Therefore, the daughter follicles may be metabolically different, e.g. in iodinating capacity. A certain degree of autonomous, i.e. TSH-dependent function is inborn to all follicles. The individual degree of autonomy of iodine turnover is not variable during goitrogenesis but determined by the metabolic individuality of the mother cell at the moment of folliculoneogenesis. These three basic processes explain the typical heterogeneity of nodular goitre. From autonomous highly iodinating cell families, autonomous "hot" daughter follicles arise which may be scattered all over the gland either as single follicles or as clusters of varying size (so-called "disseminated autonomy"). Particularly large clusters of "hot" follicles result in scintigraphically visible hot nodules, often called "toxic adenomas". Hyperthyroidism appears when the total joint autonomous hormone production of normal and "hot" follicles exceeds the requirements of the organism. The large majority of goitre nodules, including the so-called "toxic adenoma", are not true monoclonal benign neoplasias. Rather, they are built up by the same polyclonal heterogeneous follicles as extranodular goitre tissue. They have no choice but to expand in nodular fashion because they replicate within a poorly extensible network of connective tissue. This network of fibrous tissue results from scarring of multiple hemorrhagic necrosis occurring episodically during goitre growth.

Adult↗
PubMed1982

The pathogenesis of "hot" and "cold" follicles in multinodular goiters.

The prominent characteristics of euthyroid and hyperthyroid human nodular goiters are the regional variability of iodine metabolism and the appearance of "hot" autonomous follicles. No explanation for the pathogenesis of the interfollicular heterogeneity of iodine turnover has yet been offered. We have investigated whether the recently demonstrated polyclonality of normal follicular epithelia could possibly be related to goiter heterogeneity. The present work demonstrates, by means of autoradiographic and histological techniques, that single cells or tiny cell families with widely differing metabolic properties are normally present within single mouse, rat, and human thyroid follicles. In animals, intercellular heterogeneity is demonstrated in respect to 1) iodinating capacity, 2) peroxidase content, 3) endocytotic response to TSH, and 4) proneness to replicate. Moreover, [3H] thymidine labeling of stimulated mice thyroids reveals that mitotic cells are not randomly distributed; some follicles contain large colonies of rapidly replicating cells, and these clonogenic cells give rise to new follicles. Since simple goiter formation invariably implies replication of normal thyroid follicles, we conclude that the large differences in iodine turnover among the follicles of simple goiters are a consequence of the generation of new, metabolically heterogeneous follicles from genetically distinct cell clusters existing with the epithelia of all normal mother follicles.

Animals↗
PubMed1979

[Effect of 2 retinoids (vitamin A analogs) on human bronchogenic carcinoma in vivo (nu/nu mouse) and in vitro].

The antitumor effects of 2 aromatic retinoids (analogs of vitamin A) were investigated in human bronchogenic carcinomas grown in vitro and in vivo (serially transplanted in "nude" mice). In vitro, bronchogenic carcinoma cells treated with Ro 10-1670 (the free acid of an aromatic retinoid) displayed activation of the lysosomal system and increased cellular breakdown. In vivo, nu/nu-mice treated with Ro 10-9359 (the ethyl-ester of Ro 10-1670 showed inhibition of tumor growth. In the tumors, necrotic areas were intermingled with regions displaying a higher degree of keratinization as compared to those of the controls. The extracellular matrix surrounding the tumor cells of the retinoid-treated animals was increased in volume and electron density.

Animals↗
PubMed1979

[Isolation and in vitro cultivation of tumor cells from human bronchial carcinoma transplanted to the nu/nu mouse].

Isolation of pure human tumor cell lines from surgical specimens is still a difficult task. As a result, only a limited number of such cell lines is available for experimental and diagnostic work. In contrast, isolation of malignant cells from human tumors serially transplanted in "nude" mice offers many advantages. The amount of tissue obtainable is theoretically unlimited and the percentage of viable cells is usually much larger than in human surgical specimens. However, no simple and reliable technique for isolation and purification of nu/nu-mouse-grown human tumor cells has been available up to now. This preliminary communication describes such a method. Its applicability has been successfully tested on 4 human bronchogenic carcinomas from which pure tumor cell lines could be established.

Animals↗
PubMed1979

Action of cytosine arabinoside on human tumor cells isolated from malignant effusions: in vitro phosphorylation and inhibition of DNA synthesis.

Tumor cells were isolated from malignant effusions of three patients with disseminated solid tumors of different origin. Intracellular accumulation of nondiffusible cytosine arabinoside (ara-C) nucleotides was used to measure phosphorylation. Mouse leukemia L 1210 and L 1210/CA, and ara-C-resistant subline, were used as reference cells. Phosphorylation activity was similar in the cells from all three solid tumors and showed a linear increase with drug concentrations of 0.1--100 micograms/ml. In contrast to activity in L 1210 cells, the in vitro activity was not saturable at drug levels up to 100 micrograms/ml. Ara-C inhibited the incorporation of thymidine into DNA 84%--90% in the solid tumor cells at a concentration of 10 micrograms/ml. Higher drug concentrations did not result in further inhibition. In one patient, DNA synthesis of tumor cells isolated before and after intraperitoneal instillation of 1,000 mg ara-C was measured. The in vivo inhibition was found to correspond to the in vitro data. Solid tumor cells isolated from malignant effusion have no greatly reduced capacity for cellular formation of ara-C/nucleotides, but higher drug levels than achieved with conventional therapy are necessary for sufficient ara-C nucleotide synthesis.

Ascites↗
PubMed1978

[Isolation of human tumor cells: conditions for in vitro diagnostic and therapeutic studies (proceedings)].

With a view to the possible use of human tumor cells for diagnostic and therapeutic tests (e.g. determination of hormone receptors, sensitivity to cytotoxic drugs, cytotoxicity tests), an attempt has been made to isolate and cultivate pure human tumor cell populations. 49 malignant effusions from 42 patients formed the starting material. The tumor cell isolation was carried out in three steps: 1. elimination of erythrocytes by density-gradient centrifugation or osmotic lysis with triple distilled water; 2. concentration of tumor cells by lg-sedimentation; 3. elimination of adherent cells by short term cultivation in plastic tissue culture flasks. This procedure yielded 95-98% tumor cells. From these suspensions of purified tumor cells, primary cultures were successfully established by supplementing the tissue culture media with autologous effusion fluid.

Cells, Cultured↗
PubMed1976

[Malignant hyperthermia: attempt at an early diagnosis by means of determination of creatine phosphokinase (CPK) and its isoenzymes].

Creatinphosphokinase (CPK) was elevated in sera of patients with malignant hyperthermia and in sera of some of their relatives. Only the MM-isoenzyme (but not the MB- or the BB-isoenzyme) could be detected by paperchromatographic analysis. In some of the patients elevation of muscle aldolase was also observed. Thus, the appearance of the BB-isoenzyme in sera of patients with malignant hyperthermia, as described by another group of investigators, was not confirmed. No specific screening method exists as yet to detect patients with a high risk of developing this often lethal reaction to anesthesia. However, in patients without muscle disease or trauma and without prior i.m. injections, myocardial infarction or major physical strain, elevation of CPK in serum should be interpreted as meaning that malignant hyperthermia may develop during anesthesia. The pathophysiology of malignant hyperthermia is discussed.

Creatine Kinase↗