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Biomedical subjects

J Krause

Publications and source records attributed to J Krause.

At least 19 recordsLinked to original sources

Asbestos-related diseases and asbestos types used in the former GDR.

In the period from 1960 to 1990 about 1.4 million tonnes of asbestos were imported by the former German Democratic Republic (GDR) and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former counties of Magdeburg and Dresden. In the past, asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. Chrysotile was predominantly imported from the former Soviet Union, partly from Canada. Very small amounts of amphiboles came from Mozambique, but they were not processed in the counties of Magdeburg and Halle. In the German Federal State of Saxony-Anhalt, approx. 600 asbestoses, almost 2,700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas caused by asbestos were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.

Asbestos

[Evaluation of prognostic factors in preoperative therapy of endometrial carcinoma].

The authors evaluated in a group of 23 women with carcinoma of the endometrium the possibility of reliable assessment of prognostic factors and their part in the selection of a suitable surgical method. They used computed tomography for preoperative assessment of the extent of myometrial invasion which is considered from the prognostic aspect an important factor of first order. They also evaluated the contribution of CT to assessment of the state of regional lymph nodes and to assess the stage of the disease. They proved the reliability of CT in the assessment of myometrial invasion in 87% and a significant contribution to the assessment of the stage of the disease. Preoperative histological assessment of the subtype and grading of the endometrial carcinoma made it possible to differentiate patients with a low and high risk of development of a malignant neoplasm.

Endometrial Neoplasms

[Severe oropharyngeal angioedema caused by ACE inhibitor. A case report].

Inhibitors of angiotensin converting enzyme (ACE) are suspected of inducing angioedemas in up to 0.2% of all patients. These angioedemas are mainly localized in the upper airways and therefore can cause severe airway obstruction and even death due to suffocation. We report the case of a 64-year-old man, who underwent emergency tracheotomy because of severe angioedema of the larynx, which was refractory to pharmacological treatment. We conclude that patients with ACE inhibitor-induced angioedemas should be observed by monitoring in an intensive care unit to ensure the possibility of early intubation, because conventional antiallergic-antiedematous therapy by histamine-receptor antagonists and corticosteroids is an insufficient, unreliable form of therapy in severe cases. Especially otolaryngologists should know about this uncommon potentially life-threatening side-effect of ACE inhibitors.

Angioedema

Salivary duct carcinoma. Part I. A clinicopathologic evaluation and DNA image analysis of 13 cases with review of the literature.

Salivary duct carcinoma is an uncommon and relatively unknown clinically aggressive adenocarcinoma of salivary origin that histologically demonstrates a remarkable resemblance to invasive carcinoma of the breast. We report the clinicopathologic features of 13 cases that were also examined by image analysis for DNA ploidy. The results were then analyzed collectively with the less than 100 cases of salivary duct carcinoma reported in the English-language literature to define the characteristics of this unusual neoplasm. The 12 men and one woman averaged 68 years of age (range, 49 to 90 years). All tumors arose in the parotid (10 cases) or submandibular glands (three cases). Nine tumors were aneuploid, three diploid, and one was indeterminate because of insufficient tissue. Follow-up (median, 24 months) was available in 12 cases: three patients died of disease, six were alive without disease, and three died of other causes. Combining our cases with those in the literature, a total of 104 cases, confirms that salivary duct carcinoma is a highly malignant neoplasm with distinctive clinical and pathologic features. It arises almost exclusively in the major salivary glands (96% of cases), is three times more common in men, and usually occurs in patients over 50 years of age (range, 22 to 91 years). One-third of patients experience local recurrences, 59% develop positive regional lymph nodes, 46% have systemic metastases (lungs and bones), and 65% die of their disease, usually within 4 years of diagnosis. Determination of tumor ploidy has no prognostic significance. The presence of distant metastasis was the only clinicopathologic feature that was statistically associated with prognosis (p = 0.02); all patients with systemic metastasis died of disease.

Adenocarcinoma

Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein.

Salivary duct carcinoma is an infrequent highly aggressive salivary gland tumor that is histologically similar to ductal carcinoma of the breast. We studied 13 cases by immunohistochemistry for the presence of estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein to determine whether the similarity to breast carcinoma extended beyond the light microscope to the molecular level and, if so, whether these markers might have therapeutic or prognostic value. Twelve of 13 cases contained sufficient amounts of tumor tissue for evaluation. Of these 12 cases, one (8%) was positive for estrogen receptors, none was positive for progesterone receptors, five (42%) were positive for cathepsin D, and three (25%) were positive for c-erbB-2 protein. Expression of cathepsin D and c-erbB-2 protein does not appear to have prognostic significance in salivary duct carcinoma. The 8% incidence of immunopositivity for estrogen receptors and absence of progesterone receptors in salivary duct carcinoma is considerably less than that seen in breast cancer. Nevertheless, because the occurrence of systemic metastasis in salivary duct carcinoma is such an ominous development largely unresponsive to chemotherapy, antihormonal therapy, such as used in breast cancer, might be considered on a trial basis for those tumors that are estrogen receptor-positive when conventional therapeutic modalities fail.

Adenocarcinoma

Use of asbestos, health risks and induced occupational diseases in the former East Germany.

In the period from 1960 to 1990 about 1.4 million tons of asbestos were imported and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former countries of Magdeburg and Dresden. In the past asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. The asbestos was imported from the former Soviet Union, smaller amounts came from Canada. In the German Federal State of Saxony-Anhalt, approximately 600 asbestoses, almost 2700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.

Asbestos

Differential fitness returns in relation to spatial position in groups.

1. A general overview of position-related fitness differences in group-living animals is given for the first time. 2. Differential fitness returns in groups are often related to competition for resources among group members due to resource limitation. If resources are very scarce, then competition may finally lead to the disbandment of groups. The encounter-dilution effect predicts that grouping confers a benefit if the conspicuousness of large groups does not outweigh the dilution effect and each predator or parasite attacks only one (or a few) prey per encounter (Uetz & Hieber, 1993). While the encounter-dilution effect limits the number of predators and parasites a group is faced with at a given time, marginal predation and communal defence are probably the most important factors for position-related differences in predation risk. 3. Limitation of resources increases competition between groups members and should widen the gap between fitness returns of dominant and subordinate group members. In some group-living animals such as schooling fish, however, predator pressure has apparently selected for uniformity in morphology and behaviour which presumably restricts the potential for resource competition (Magurran & Seghers, 1991). 4. A general problem of assessing individual fitness returns in that different short-term strategies may achieve the same long term goals (Magurran, 1993). The use of feeding rates and predation risks as currencies for fitness returns over short time periods is therefore questionable and can only be a first step. So far, hardly any information is available on long-term effects of differences in positioning behaviour. 5. Food availability and food intake rates tend to be higher in edge positions, whereas energy expenditure does not differ significantly with group position in non-roosting mobile groups. This suggests that edge positions achieve a higher net-energy pay-off and should therefore be preferred by individuals with low energy reserves. 6. Differential predation risks are well documented for stationary and colony-breeding species, but there is a lack of data for mobile, non-breeding species. The reason for the latter is that predation is rarely observed (in the field) and often difficult to relate to group position in fast-moving species such as flocks of birds. Further studies, especially in the field, are needed. 7. Vigilance rates and attack rates do not necessarily give a true reflection of mortality risk. Vigilance is not exclusively related to predation and can be confounded by competition effects and hunger. Attack rates are difficult to translate into per capita risks if hardly any mortality is observed and therefore little information is available about the ratio of successful attacks/total attacks. 8. Most of the literature up to date consists of descriptive studies. There is a need for experimental work that investigate (a) the influence of predator attack mode on differential predation risks; (b) the influence of internal states (such as hunger) on the tradeoff between predation risk and foraging behaviour and its consequences for the positioning behaviour in groups; (c) the 'egalitarian' nature of groups with respect to group position. Do all individuals continuously rotate positions? Or do dominant individuals monopolize certain positions?, and (d) that separate the effects of nutritional state, vigilance and food availability on feeding rates in different group positions. 9. Reproductive success is often related to group position in breeding colonies and lekking animal species. Females probably prefer the safer territories in the group centre, but more empirical data are required to test this hypothesis. 10. Position-related differences in parasitism rate between group members are well documented with per capita rate of parasitism being lower in the centre of groups than at the periphery.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Influence of sequential exposure to R-verapamil or B8509-035 on rhodamine 123 accumulation in human lymphoblastoid cell lines.

Modulators for the reversal of multidrug resistance such as R-verapamil and B8509-035, a dihydropyridine, effectively overcome multidrug resistance in vitro and are currently undergoing clinical trial. One problem with their use is the application protocol; the question as to whether they should be given by continuous administration or in sequential doses in combination with the cytotoxic drugs has to be addressed. Therefore, we examined the influence of the exposure time and the sequence of modulator administration on the active transport of the fluorescent dye rhodamine 123 (R123), a substrate for the P-glycoprotein, in the resistant lymphoblastoid cell line VCR1000 and the parental nonresistant cell line CCRF-CEM. Our results demonstrate the importance of coadministration of R-verapamil and the cytotoxic agent for the modulation of multidrug resistance, whereas the exposure sequence does not seem to be such an essential parameter in the case of B8509-035. This observation should be considered for the further design of clinical studies.

ATP Binding Cassette Transporter, Subfamily B, Mem

Evidence for carbohydrate-independent endocytosis of tissue-type plasminogen activator by liver cells.

In the liver, tissue-type plasminogen activator (t-PA) is endocytosed by hepatic parenchymal (PC), endothelial (EC) and Kupffer (KC) cells. Although the endocytosis is receptor-mediated, it remains a matter of discussion which receptors are involved in this catabolic process. To evaluate the role of a protein-specific receptor, as well as the possible involvement of the galactose receptor on PC and the mannose receptor on EC, we have employed different glycosylation variants of t-PA in biochemical and immunocytochemical studies. Partial or total removal of carbohydrate side-chains by endoglycosidases did not prevent clearance and hepatic endocytosis of t-PA by either of the liver cell types. Blockade of the galactose and mannose receptors by co-application of a large excess of the glycoprotein ovalbumin remained without effect on the binding and uptake of t-PA by hepatic cells. However, the contribution of different liver cell types to the hepatic clearance of t-PA was to a certain extent dependent on the type of oligosaccharide chains removed. The mannose receptor on EC is partially responsible for the clearance of t-PA by this cell type, whereas the galactose receptor does not seem to be involved in this process. The results obtained in this study further demonstrate that the major portion of the hepatic catabolism of t-PA is independent of its carbohydrate side-chains.

Amidohydrolases

[Anti-basement membrane antibody disease of the lungs without clinical kidney involvement].

Anaemia (haemoglobin 10.7 g/dl) and small spotty infiltrates in both lungs were found in an 18-year-old man who had increasing haemoptysis over the preceding 3 weeks. Bronchoscopy revealed diffuse bilateral pulmonary haemorrhage. Further diagnostic measures provided no evidence of involvement of other organs, in particular the kidneys. The demonstration of anti-basement membrane antibodies confirmed the diagnosis of a disease within the group of immune-induced alveolar haemorrhage. The radiological signs in the lungs regressed over 3 weeks of administering prednisone, initially 100 mg daily, then 60 mg daily, and the patient was discharged. While being treated as an out-patient, with reduction of prednisone to 10 mg daily, the haemoptysis recurred so that a single dose of cyclophosphamide, 1.5 g, was added to the immunosuppressive treatment. There was no further haemoptysis and the prednisone was discontinued after having been given for 15 months. The patient has now been in complete clinical remission for 3 years and anti-basement membrane antibodies are no longer demonstrable. At no time was there any evidence of renal involvement in the sense of the classical Goodpasture's syndrome.

Adolescent

Endocytosis and intracellular processing of tissue-type plasminogen activator by rat liver cells in vivo.

Endocytosis of tissue-type plasminogen activator (t-PA) by different types of rat liver cells was studied in immunocytochemically labelled cryosections as well as in biochemical experiments. For morphological localization of the ligand in different endocytic compartments involved in its catabolism, rat livers were fixed at various times (1-24 min) after injection of t-PA. Late-endosomal and lysosomal compartments were identified by double-labelling the sections with antibodies to the lysosomal proteins glycoprotein Igp 120 and cathepsin D. In liver t-PA was localized in sinusoidal endothelial cells (EC), parenchymal cells (PC) and to some extent in Kupffer cells (KC), indicating that it is internalized and degraded in all three cell types. In specimens fixed 6 min after injection PC, EC and KC were found to contribute to 69, 24 and 7% respectively of total t-PA endocytosed. The transfer from late endosomes to lysosomes was found to be faster in EC than in PC. The morphological findings were supported by studies of the endocytic mechanisms employing isolated perfused livers and primary hepatocytes. The presence of monensin, an inhibitor of lysosomal protein degradation, reduced the amount of t-PA degraded to about 50% of the control values. The catalytic site seems not to be required for the catabolism of t-PA in hepatic cells. The inhibition of t-PA by D-phenylalanyl-L-prolylarginyl-chloromethane did not influence receptor recognition and catabolic processing, as determined in morphological studies using labelled cryosections, in binding studies employing liver cell membranes and primary hepatocytes, as well as in liver-perfusion experiments.

Animals

[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma].

Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.

Antibodies

[Tumor proliferation, MDR phenotype and tumor associated t-lymphocytes in non-Hodgkin's lymphomas].

In this study we examined the P170-expression (mdr-phenotype) in 42 non-Hodgkin's Lymphomas with variant entities immunohistochemically with the mab JSB1. The mdr-phenotype was related to the tumor proliferation as measured by Ki67-expression and AgNOR numbers. Furthermore the mdr-phenotype was related to the tumor associated T-lymphocytes. The mdr-phenotype showed no relation to histological type and the proliferation of the tumor. There was a positive correlation between the mdr-phenotype and CD2-reactive lymphocytes. There was also a significant positive correlation between CD4-reactive lymphocytes and the mean number of AgNOR's. Possibly P170-expression and proliferation of the tumor cells have a lymphotactic effect on T-lymphocytes. The latter could promote tumor progression by means of paracrine mechanisms.

CD4 Antigens

Neuropeptide Y1 subtype pharmacology of a recombinantly expressed neuropeptide receptor.

Neuropeptide Y (NPY) is an important central and peripheral modulator of neural and endocrine functions. This neuropeptide interacts with at least two pharmacologically distinct receptors, termed Y1 and Y2. At Y1 receptors, the NPY analog [Leu31,Pro34] NPY, but not the carboxyl-terminal fragment NPY-(18-36), displaces radiolabeled NPY and the sequence-related peptide YY, whereas Y2 receptors exhibit the opposite selectivity. We have used cultured mammalian 293 cells for the high level transient expression of a previously cloned putative neuropeptide receptor of rat brain. We report that this receptor displays the ligand binding properties and selectivity of a Y1 receptor, with a single high affinity site for 125I-NPY (Kd, 0.7 +/- 0.2 nM). The functionality of the recombinantly expressed receptor was demonstrated by an inhibition of adenylyl cyclase and a concomitant mobilization of intracellular Ca2+.

Amino Acid Sequence

Different neuropeptide Y receptor subtypes in rat and rabbit vas deferens.

Prejunctional neuropeptide Y (NPY) receptors that inhibit the contractions evoked in rat and rabbit vas deferens by field stimulation were investigated by using NPY, [Leu31,Pro34]NPY and the fragments, NPY-(13-36) and NPY-(18-36). NPY, and especially [Leu31,Pro34]NPY, were more potent agonists on the twitch response of the rabbit vas deferens. In contrast the NPY C-terminal fragments, NPY-(13-36) and NPY-(18-36), inhibited the twitch response at lower concentrations in the rat vas deferens. These results indicate that distinct NPY receptor subtypes mediate the biological effect in these two tissues. We suggest that prejunctional receptors in the rat vas deferens are of the Y2-subtype and those in rabbit vas deferens of the Y1-subtype.

Animals

An interdisciplinary study towards a multiaxial classification of male sexual dysfunction.

The classification of male sexual dysfunction (SD) was investigated in a multidisciplinary study involving a sample of 25 outpatients whose phenomenology, course and biologic comorbidity is described. All 25 patients were suffering from arousal disorders; 9 men complained of lack of desire and 9 of orgasm disorders. For the vast majority (19/25), the arousal disorder preceded the other sexual dysfunctions. Eleven patients suffered from a psychopathological disorder according to DSM-III or DSM-III-R (Axis I and II), with general anxiety, major depression and obsessive-compulsive personality being the most common disorders. Only 6 patients were free of any organic disorder or pathological laboratory finding known to be related to sexual dysfunction. These results served as the basis for analyzing the fit of our data in the most prominent classification systems DSM-III, DSM-III-R, Mainz multiaxial classification model and the traditional dichotomy model. According to our data, the comorbidity of biologic and mental conditions was very high, as most patients (60%) suffered from more than one etiologic factor known to be related to SD. Based on these results, a modification of the DSM-III-R system is suggested.

Adolescent