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Biomedical subjects

M Schardt

Publications and source records attributed to M Schardt.

At least 19 recordsLinked to original sources
PubMed2000

Endocrine host responses during early and late phases of tumor development.

It is well established that hormones affect tumor growth. Conversely, inoculation of cells obtained from tumors that had been transplanted for many generations causes changes in the concentration of different hormones before and after tumor detection. We aimed at answering the question of whether hormonal alterations also occur during the development of primary tumors and following transplantation of tumors from early generations. Primary tumors were induced in mice by either the carcinogenic agent 3-methylcholanthrene, which produces fibrosarcomas, or the milk-transmitted mammary tumor virus, which induces adenocarcinomas. The results showed that (i) in both models, an early reduction in plasma insulin and prolactin levels occurred, and in the case of insulin, this reduction was sustained for a prolong period prior to tumor detection, indicating that recognition by the host of emergent tumor cells triggers an endocrine response; (ii) in contrast with multiply transplanted tumors, cells from early transplant generations produced no significant endocrine changes during latency; (iii) irrespective of whether they were primary or transplanted, large tumor burdens caused similar hormonal alterations, consisting of increased corticosterone and growth hormone and decreased insulin, thyroxin, prolactin and sex steroid levels in blood. Our comprehensive longitudinal study demonstrates host endocrine responses during different stages of neoplastic development.

Animals↗
PubMed2000

A reduction in blood insulin levels as a host endocrine response during tumor development.

It has been previously reported that endogenous insulin levels decrease during tumor growth. We have now studied whether this host endocrine response is independent of the way in which the tumor is induced. For this purpose, animals transplanted with tumor cells induced by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a) anthracene (DMBA), or with EL-4 lymphoma cells, and animals that develop autochthonous tumors induced by MCA or the murine mammary tumor virus (MMTV) were used. These procedures result in the induction of tumors of different histologic types: fibrosarcoma, mammary adenocarcinoma and lymphoma. The results obtained showed that a reduction in insulin levels preceded the overt appearance of tumors in all models of syngeneic or autochthonous tumors studied but not when DMBA-induced tumor cells were administered into allogeneic recipients. Reduced levels of insulin before tumor detection appeared to affect the onset of MCA-induced tumors. Indeed, those mice with a late tumor onset were those that had a more pronounced decrease in insulin blood levels during the induction phase of autochthonous MCA-induced tumors. Soluble factors associated with tumor growth seem to mediate the reduction in insulin blood levels in mice transplanted with EL-4 tumor cells. The results obtained indicate that the reduction in insulin levels detected is a consequence of the recognition of tumor cells by the host, and seems to be independent of the histologic type of the neoplastic cells that develop. Pharmacological interventions at the levels of mechanisms that control insulin output should clarify the relevance of decreased levels of this hormone for tumor development.

Animals↗
PubMed1997

A hybrid classifier for remote sensing applications.

This paper presents a hybrid-unsupervised and supervised-classifier for land use classification of remote sensing images. The entire satellite image is quantized by an unsupervised Neural Gas process and the resulting codebook is labeled by a supervised majority voting process using the ground truth. The performance of the classifier is similar to that of Maximum Likelihood and is only a little worse than Multilayer Perceptions while training and classifying requires no expert knowledge after collecting the ground truth. The hybrid classifier is much better suited to classifications with complex non-normally distributed classes than Maximum Likelihood. The main advantage of the Neural Gas classifier, however, is that it requires much less user interaction than other classifiers, especially Maximum Likelihood.

Algorithms↗
PubMed1992

Modified meatal advancement and glanduloplasty with complete foreskin reconstruction.

We report 28 boys who underwent repair of a distal hypospadias with a combination of a modified meatal advancement and glanduloplasty and reconstruction of the foreskin. An excellent result was achieved in 24 patients. In 4 boys, preputial reconstruction failed. Only one group of parents demanded further surgery. Improved cosmetic results with avoidance of serious complications make this operation ideal for treating distal hypospadias in countries where the circumcised penis is an exception.

Child, Preschool↗
PubMed1991

On the mechanism of antiinflammation induced by tumor transplantation, surgery, and irritant injection.

Tumor transplantation, major surgery, and injection of nonspecific irritants elicit inflammation locally while suppressing inflammation induced subsequently and at distant sites. Such systemic antiinflammation in rodents occurs via corticosterone-independent and -dependent pathways. Based upon hormone measurements and the response to adrenalectomy, antiinflammation induced by irritants and certain surgical procedures is corticosterone independent while that which follows tumor transplantation is corticosterone dependent. However, injection of tumorous ascites stimulates both pathways since it contains two antiinflammatory factors: Factor A (molecular weight less than 2,000) does not alter hormone balance while Factor B (molecular weight 30,000-100,000) increases corticosterone levels and is corticosterone dependent. Desensitization of systemic antiinflammation develops rapidly regardless of whether it is corticosterone dependent (Factor B) or independent (Factor A or irritants). However, tumor transplantation resists desensitization possibly by inducing an immune response since lymphocytic mitogens prevent development of and break established desensitization. Nevertheless, abolition of tumor-induced antiinflammation follows injection of tumorous ascites by a mechanism that involves Factor B suppression of the corticosterone response to the tumor while Factor A apparently raises the threshold at which physiological increases in corticosterone inhibit leukocyte emigration. We conclude that systemic antiinflammation is a general consequence of a localized inflammatory reaction and that desensitization of such antiinflammation develops rapidly. Recent evidence indicates that certain mediators of inflammation are proinflammatory when administered intradermally but antiinflammatory when given intravenously. Thus, systemic antiinflammation may arise when chemical mediators of inflammation generated by a local reaction gain access to the circulation.

Adrenalectomy↗
PubMed1988

Hormonal changes following tumor transplantation: factors increasing corticosterone and the relationship of corticosterone to tumor-induced anti-inflammation.

EL-4 lymphoma cells transplanted to syngeneic C57BL/6J mice induced a biphasic decrease in inflammation and a bi-phasic increase in serum levels of corticosterone. In addition, this tumor altered serum levels of 3 other hormones, resulting in a biphasic decrease in insulin, an early decrease in prolactin, and a terminal severe deficiency in thyroxine. Early changes occurred 16 to 48 hr after tumor transplantation and were of variable duration, while late-phase defects developed during the last few days of life. Soluble factors associated with tumor growth may mediate certain hormonal changes since serum levels of corticosterone increased and insulin decreased following injection of tumorous ascites into normal mice. Further, injection of cell-free tumor culture supernatants increased corticosterone levels. Hormonal changes following injection of soluble factors occurred after a delay of 16 hr indicating that the factors acted indirectly. Surgical adrenalectomy blocked the corticosterone increase induced by tumor transplantation or ascites injection and eliminated the anti-inflammatory effect of tumor transplantation while significantly decreasing the effect associated with injection of tumorous ascites. Thus, the physiologically induced increase in serum levels of corticosterone reached anti-inflammatory levels. Further, elevated levels of corticosterone are a major contributing factor to anti-inflammation induced by tumorous ascites injection and constitute the principal mechanism of anti-inflammation following tumor transplantation.

Animals↗
PubMed1988

Interactions between endogenous glucocorticoids and inflammatory responses in normal and tumor-bearing mice: role of T cells.

Appropriately stimulated lymphocytes and macrophages produce factors in vitro that increase serum corticosterone levels when injected in vivo. In this study, we used euthymic and congenitally athymic mice on a BALB/c background to explore the role of T cells in controlling corticosterone levels and the leukocyte response to inflammation. Adult athymic mice had more intense inflammatory reactions than euthymic mice despite higher basal corticosterone levels. This latter condition may be due to interleukin-1 (IL-1) since macrophages from athymic mice when stimulated in vitro by lipopolysaccharide produced more IL-1 than macrophages from euthymic mice. In response to mitogen stimulation, however, splenocytes from athymic mice produced a factor (not IL-1), which, upon injection, increased corticosterone levels and suppressed inflammation. Production of this factor was enhanced by T cells since splenocyte supernatants from euthymic mice were more potent in eliciting both effects. Evidence for in vivo participation of T cells in regulating corticosterone levels was obtained by tumor transplantation. Injection of syngeneic tumor cells or cell-free tumorous ascites rapidly increased corticosterone levels in euthymic but not athymic mice. Anti-inflammation correlated with increased corticosterone levels but was observed also in athymic mice receiving syngeneic tumor transplants. These studies demonstrate that T cells enhance production of a lymphokine that increases corticosterone levels and are required for the corticosterone response to tumor transplantation. In addition, the data suggest two pathways of anti-inflammation in tumor-bearing hosts: a corticosterone-independent, T cell-independent mechanism and a T cell-dependent mechanism that involves a lymphokine-mediated increase in corticosterone blood levels.

Animals↗
PubMed1987

Cancer induced anti-inflammation and its potentiation by tumor excision and rechallenge.

Tumor rechallenge following primary tumor excision elicits systemic anti-inflammation that occurs rapidly, affects granulocytes as well as macrophages and is more severe, longer in duration, and induced by fewer tumor cells than the macrophage specific anti-inflammatory effect sometimes seen after primary tumor challenge. Factors important in the pathogenesis of this abnormality are the following. First, primary tumor excision was required as defects did not occur when a second tumor was transplanted during primary tumor growth. Second, the abnormality was restricted to neoplastic cells since normal cells were unable to substitute for either primary or secondary tumor challenge. Third, the anti-inflammatory effect was not due to surgical trauma or local irritation. Fourth, defective inflammation occurred in syngeneic but not allogeneic rats, suggesting an immunological basis for the anti-inflammation. Fifth, elevated glucocorticoids, such as might be expected from an immunological reaction or release of IL-1, may be a contributing but not sole cause for the phenomenon.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Changes in plasma hormone profiles after tumor transplantation into syngeneic and allogeneic rats.

Transplantation of 2 chemically (DMBA, MCA)-induced tumors into syngeneic female or male DA strain rats elicited hormonal changes during tumor growth. Plasma levels of 7 different hormones were studied. Tumor cells in syngeneic recipients produced a biphasic decrease in insulin, an early increase in prolactin, and a late-phase decrease in thyroxine. Corticosterone decreased in female tumor bearers but increased in males. This difference may reflect differences in the tumors transplanted. Male rats had a decrease in testosterone during the late phase of tumor growth, while females had a biphasic decrease in progesterone and a late-phase increase in growth hormone. The tumors used were moderately immunogenic in syngeneic recipients. However, tumor transplantation to allogeneic recipients produced an early decrease in growth hormone and no change in insulin, corticosterone or thyroxine. Further, transplantation of normal liver cells to syngeneic or allogeneic recipients produced no hormonal abnormalities. This study demonstrates that hormonal changes which are not observed with normal cells or allogeneic tumor transplantation can occur within 2 days of syngeneic tumor transplantation. Progressive tumor growth is characterized by a worsening endocrine imbalance which involves multiple hormone systems.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Antileukocyte activity I. Systemic inhibition of cellular emigration following local inflammation.

Inflammation in progress at one site decreases edema formation at a second and separate inflammatory focus. This clinically important phenomenon is known as counter-irritation. Since its effect on leukocyte responses has not been defined, we investigated in rats the systemic anti-inflammatory effect of local irritant injection on cellular emigration, particularly monocytes. Macrophage accumulation at a subcutaneous inflammatory site was severely depressed by prior intraperitoneal irritant injection despite continued macrophage accumulation in the peritoneal cavity and normal circulating monocyte levels. The phenomenon also existed in the peritoneal cavity to subcutaneously administered irritants and involved PMNs as readily as macrophages. Anti-inflammation occurred only when the counter-irritant was injected before or simultaneously with the measured inflammatory response while the degree and duration of inhibition depended upon the nature and amount of counter-irritant injected. These studies demonstrate that local inflammation inhibits leukocyte reactivity. Transplantation of syngeneic tumor but not normal cells also produced a depression in macrophage inflammatory responses. This inhibition differed from counter-irritation by not affecting granulocytes and by being transient despite tumor persistence.

Animals↗
PubMed1985

Antileukocyte activity II. Induction of tolerance to systemic anti-inflammation associated with local irritation and major surgery.

Anergy associated with cancer or major surgery may derive from the systemic antileukocyte effect induced by local inflammatory reactions (counter-irritation). Since the mechanism of the latter phenomenon is unknown, we approached the problem by asking if tolerance develops to repeated local irritant injections. Our results demonstrate that both tolerance and cross-desensitization occur rapidly to inflammatory agents (inflammagens) such as proteose peptone, thioglycollate, and carrageenan but not to the mitogens Con A, PHA-P, or LPS which also induce local inflammation. We interpret this data as supporting the notion that a common mechanism underlies the counter-irritant action of inflammagens but that injection of mitogens induces an additional mechanism of anti-inflammation distinguished from the former by its lack of tolerance induction. Based upon cross-desensitization experiments, we show that the anti-inflammatory effect of surgical amputation is analogous to that induced by inflammagens. In contrast, the systemic anti-inflammatory effect of tumor bearing, like that induced by mitogens, resists cross-desensitization suggesting that its mediation is not caused solely by the mechanism common to the counter-irritant action of inflammagens or major surgery.

Amputation, Surgical↗
PubMed1985

Autochthonous murine tumors: effects of viral or ultraviolet induction, immunogenicity and transplantation on intratumoral macrophages and systemic inflammatory responses.

Macrophage tumoricidal activity requires a constant influx of macrophages but many transplanted cancers inhibit macrophage inflammatory responses. In this paper we address the issue of whether or not autochthonous tumors induced by either mammary tumor virus (MTV) in C3H/He mice or ultraviolet (u.v.) radiation in C3H/He or BALB/c mice also depress macrophage responses. Anti-inflammatory activity was not observed either prior to or during growth of these autochthonous tumors. Rather, the opposite was observed: strongly immunogenic u.v.-induced tumors which were rejected upon transplantation to syngeneic hosts had enhanced macrophage responses and more intratumoral macrophages than those mice whose tumors were transplantable. Transplantation of MTV-induced tumors selected for more aggressive tumors which had fewer intratumoral macrophages. In both MTV- and u.v.-induced tumors inflammatory responses of mice bearing serially transplanted tumors often differed from mice with autochthonous tumors. Our results demonstrate that anti-inflammation is probably not required for emergence and growth of these autochthonous tumors, that strongly immunogenic tumors may actually enhance macrophage responses and that the effect of tumor bearing on macrophage inflammation is a characteristic of the tumor, including its site and host of origin, its immunogenicity and its transplant generation.

Animals↗
PubMed1984

Dissociation of chemotactic and inflammatory leukocyte responses.

Leukocyte accumulation at inflammatory sites probably involves chemotactic migration of the cells, and it is often presumed that abnormalities in cell accumulation derive from defective chemotaxis. The latter contention was examined by measuring the chemotactic response of leukocytes obtained from the circulation during conditions associated with depressed cellular inflammatory reactions. In two transplanted-tumor models induced by different chemical carcinogens in DA strain rats, monocyte chemotaxis was normal or enhanced while macrophage accumulation at inflammatory foci was severely curtailed. Late pregnancy in outbred Wistar rats depressed macrophage accumulation to peritoneal irritants while enhancing monocyte chemotaxis. Irritant-induced anti-inflammation (counterirritation) in Wistar rats decreased both polymorphonuclear leukocyte and macrophage accumulation during inflammation but enhanced the chemotactic activity of the corresponding cells obtained from the circulation. We concluded that in vitro chemotactic measurements were not predictive of cellular accumulation during inflammation in these conditions and that an intrinsic defect in chemotaxis was insufficient to explain anti-inflammation associated with cancer, pregnancy, or counterirritation.

Animals↗
PubMed1983

Lymphocytotoxicity for oral mucosa in lichen planus.

The in vitro effect of peripheral blood lymphocytes on syngeneic oral epithelial cells was investigated in 23 patients suffering from lichen planus of skin and/or mucous membranes and in 18 healthy sex- and age-matched volunteers as controls. A modified 51Cr release macro-assay was used. The result shows a significant lymphocytotoxic effect on the epithelial target cells, giving evidence of cytolytic activities of blood lymphocytes on autologous epithelial cells. We consider these lymphocytes to be involved in the complex pathogenesis of lichen planus.

Adult↗
PubMed1982

Effect of pregnancy of cellular inflammation.

Pregnancy inhibits macrophage accumulation within the peritoneal cavity of Wistar rats when inflammation is induced by phytohaemagglutinin (PHA). The inhibition of macrophages was considerably greater than that of polymorphonuclear leucocytes (PMNs) induced by sodium caseinate. Pregnancy did not significantly alter macrophage accumulation to PHA injected into the pleural space or to nitrocellulose filters placed s.c. Cell-free homogenates prepared from the products of conception, but not normal liver, contained an anti-flammatory factor which, when injected i.v., inhibited macrophage accumulation to peritoneal but not to pleural or s.c. irritants. The responsible anti-inflammatory factor was identified as a peptide of mol. wt less than 1000.

Animals↗
PubMed1981

Biphasic depression of macrophage function after tumor transplantation.

Tumor bearing produces a biphasic depression of macrophage inflammatory responses. Macrophage accumulation was measured on nitrocellulose filters in DA rats transplanted with a DMBA-induced fibrosarcoma and in SJL/J mice transplanted with a first-generation histiocytic lymphoma. The early phase defect was observed 2-5 days and 4-12 days after tumor transplantation in rats and mice respectively. Although transient, its duration could be prolonged by increasing the number of tumor cells injected. An interval of normal responses separated this early defect from a second or late-phase defect which began midway in the clinical course and persisted until death. Transplantation of syngeneic liver cells increased macrophage responses in DA rate but had no effect in SJL/J mice. The demonstration of a biphasic anti-inflammatory effect following tumor transplantation suggests that low doses of tumor cells are effective in inhibiting macrophages and that tumor bearing may alter macrophage responses by more than one mechanism.

Animals↗
PubMed1981

Alteration of macrophage function in AKR leukemia.

A virally induced T-cell leukemia-lymphoma developed spontaneously in 80% of inbred AKR mice between the ages of 6 and 12 months. Advanced cancer inhibited macrophage accumulation at inflammatory sites, with the degree of inhibition being directly related to the elevation in peripheral white blood cell (WBC) count and inversely correlated with the weight of the tumorous lymph nodes and thymus. Sixty AKR mice were examined biweekly between the ages of 5 1/2 and 10 months; macrophage inflammatory responses were compared with peripheral WBC counts. Depressed macrophage responses were not observed before onset of leukemia but did occur coincidently with or within 2 weeks of each episode of leukemia. The conclusion was reached that an inhibition of macrophage function typically occurred with the onset of spontaneous leukemia and during the terminal phase of illness, but this inhibition did not precede leukemia, was probably not related to lymph node or thymus enlargement, and was not always present despite persistent tumor growth.

Age Factors↗