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Biomedical subjects

H Ludwig

Publications and source records attributed to H Ludwig.

At least 163 records · Page 9Linked to original sources
PubMed1994

[Smoking and the risk of cancer].

Consumption of tobacco, alone and in combination with alcohol, is one of the most important factors in the development of cancer. Besides lung cancer, the neoplasms of the oral cavity, the larynx, the esophagus, the pancreas, the kidneys and the bladder rank among the tobacco-related cancers. But also stomach and cervical cancer are connected with the use of tobacco. Passive smokers are confronted with a higher risk of lung cancer, and the risk of developing childhood cancer (e.g. Wilms tumor, acute lymphoblastic leukemia, non-Hodgkin's lymphoma) has been widely considered to be correlated with smoking by the mother during pregnancy. Many investigators are now trying to identify risk groups of smokers to decrease the rate of cancer cases and deaths. Although this research is of great interest, it would be of course much more effective to prevent the risks by not smoking. Epidemiologists estimate, that approximately 30% of all cancer cases could be avoided by this means.

Alcohol Drinking↗
PubMed1994

Genome organization of the herpesviruses: minireview.

Fundamentally, the members of the herpesvirus family can be divided into six genome structure types designated by the letters A-F. Most of the viruses relevant to animal diseases belong to the D or E type. Whereas the biological function of the different DNA structures is so far unknown, studies on HSV genome structures indicate a rolling-circle mechanism as a mode of virus replication. Furthermore, the terminal repetitive segments seem to be involved in cleavage/packaging mechanisms and probably in the integration process of virus into the host genome. In the well-studied D and E type viruses a great number of genes are colinearly arranged and are homologous regarding their sequences. Thus genes encoding alpha-proteins map at least in part within the reiterated sequences, whereas beta- and gamma-polypeptide genes are largely located within the unique sequences of the long and short components.

Genome, Viral↗
PubMed1994

[The treatment of multiple myeloma].

Median survival in patients with multiple myeloma, which amounted to 6-12 months during the pre-chemotherapy era, was improved to 28-43 months following the introduction of chemotherapy. Usually patients with stage II or III myeloma require treatment. Conventional chemotherapy with melphalan-prednisone is undertaken if their prognosis is good; in case of poor prognosis and good general condition, a more aggressive polychemotherapy is given. High-dose melphalan therapy alone induces high remission rates, but fails to prolong remission duration or survival. Resistance to cytostatic drugs due to the p-glycoprotein coded by the MDR-gene is treated by a combination of cyclosporin-A or verapamil and VAD. For the treatment of relapses or of primarily resistant patients several second-line regimens are available. As remission maintenance therapy, interferon has so far yielded the best results. Trials of other cytokines such as interleukin-2 and interleukin-4 are still inconclusive. For autologous bone marrow transplantation, primary reduction of the tumour mass by conventional polychemotherapy is recommended. Subsequently, high-dose melphalan or cyclophosphamide-busulfan--with or without total body irradiation--is used for conditioning and followed by the transplantation of either autologous bone marrow or peripheral blood stem cells. Significantly higher remission rates and longer survival of the patients may be expected. Allogenous bone marrow transplantation is burdened with a high early mortality rate, but it also promises longer disease-free survival times. Bone marrow transplantation should be performed as early as possible in the course of the disease. More controlled studies are required before a definite evaluation of its efficacy is possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A rapid FISH technique for quantitative microscopy.

Results of quantitative microscopy for fluorescence in situ hybridization (FISH) signals with repetitive DNA probes (pUC 1.77 and D15Z1) are reported. A nonenzymatic hybridization technique was applied using fluorescein-12-dUTP labeled DNA probes and a buffer system not containing any formamide or equivalent chemical denaturing agents. Following thermal denaturation, the renaturation time was reduced to less than 30 min. The number of wash steps was reduced to one. For the pUC 1.77 probe, the major binding sites (chromosome 1) were distinguished from the minor binding sites by means of fluorescence intensity and spot size. The intensity variation of the two brightest FISH spots (major binding sites) in the same metaphase was 19% for 15 min renaturation time and 16% for 30 min renaturation time. For the D15Z1 probe, generally four bright spots were visible and tentatively assigned according to chromosome length and centromere position (chromosomes 15 and 9). The intensity variation of each two homologues in the same metaphase spread showed a coefficient of variation of 47% (15 min) and 22% (30 min) for chromosome 15, and 19% (15 min) and 15% (30 min) for chromosome 9. The results indicate that the applied technique can considerably accelerate the FISH procedure and is suited for quantitative microscopy.

DNA Probes↗
PubMed1994

[Menarche].

Menarche is one of the most important biologic signals in the life of a woman. Its importance is reflected by the wide attention which this theme has provoked in today's psychologic and anthropologic literature. Educational points should play their role next to the humanistic value of cyclic bleeding in the female self-assurance. Education for understanding of menstruation should stress that it primarily expresses femininity and should avoid depicting menstrual bleedings as a repetitive nuisance. The timing of menarche is determined by reaching a certain body weight. It is the adipose tissue of the adolescent girl that takes in many ways part in the synchronization of the future reproductive functions. In comparison to what has been observed through the past centuries, growth and bodily maturation of young girls is accelerated today. That acceleration depends rather on nutritional factors from early childhood than on a so-called trauma of urbanization. When girls experience their first menstruation, affirmative as well as negative attitudes can be observed. Hygienic details should be addressed when menarche is impending. Pads (sanitary towels) are first choice, but under particular circumstances tampons may be used as well. The description of toxic-shock syndrome after tampons were left intravaginally was a scientific hit a decade ago, but this syndrome does not play an important role in Europe and never has. However, long duration and/or severity of bleeding should prompt a differentiated diagnosis and certainly calls for medical control.

Adolescent↗
PubMed1993

The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer.

BACKGROUND: Proliferating cell nuclear antigen (PCNA), a proliferation marker, epidermal growth factor receptor (EGFR), a glycoprotein that plays a role in tumorigenesis by binding the mitogenic epidermal growth factor, and P-glycoprotein, the mdr gene product, are considered to be of prognostic relevance in different tumor types. Parameters that allow prediction of the course of disease in colorectal cancer would aid the development of improved treatment strategies. METHODS: Immunohistochemical staining was performed on paraffin-embedded sections of 82 colorectal adenocarcinomas and 18 lymph node metastases. EGFR and P glycoprotein expression was evaluated semiquantitatively; PCNA expression was analyzed quantitatively. RESULTS: An inverse relationship between the percentage of PCNA-positive cells and survival times could be demonstrated, survival differed significantly among the quartiles (P < 0.02). The median and range of the percentage of PCNA-positive cells in primary tumors and lymph node metastases were similar. The extent of EGFR expression also revealed significant differences concerning survival times; patients with more than 50% stained tumor cells had a poorer prognosis than those with less than 50% stained cells. P-glycoprotein expression was found to have no influence on survival. CONCLUSIONS: Knowledge of the percentage of PCNA-positive cells could be especially helpful in deciding whether to treat patients with localized disease further because adjuvant chemotherapy affects mainly dividing cells and should, therefore, be more successful in tumors with high proliferative activity.

Adult↗
PubMed1993

Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma.

Recombinant human erythropoietin (rHuEPO) improves chronic anemia of cancer, but the proportion of patients who respond favorably to the treatment varies depending on the type of neoplasia. Preliminary data of the two malignancies with the highest response rates, namely, multiple myeloma and squamous cell carcinoma, are reported. Twenty patients with multiple myeloma and 14 with squamous cell carcinoma, who had presented with hemoglobin levels < 11 g/dl, were treated with rHuEPO, 150 U/kg, three times/week. Response, defined as an increase of at least 2 g/dl hemoglobin within 12 weeks, was achieved by 15 myeloma patients (75%) and 11 patients with squamous cell carcinoma (79%). Tolerance of the treatment was excellent. The WHO performance status and quality of life improved in responders. The remarkably low levels of endogenous EPO in our patients with squamous cell carcinoma, most of whom had been treated with cisplatin-or carboplatin-containing regimens, suggest that anemia in these cases had been at least partly chemotherapy induced. In myeloma patients, the blunted EPO response to the anemic condition may have been partly caused by subclinical tubular insufficiency induced by toxic paraproteins. Future studies should aim to elucidate factors which are responsible for the inability of some patients to respond to rHuEPO treatment, even though in multiple myeloma and squamous cell carcinoma these non-responders are a small minority.

Anemia↗
PubMed1993

Biology and neurobiology of Borna disease viruses (BDV), defined by antibodies, neutralizability and their pathogenic potential.

Borna disease viruses (BDV) isolated from more than 20 naturally infected horses, 2 sheep and a possible feline isolate were included in these studies. Most of these wild-type viruses were grown in rabbit cells. Specifically rabbit-adapted viruses establish persistent infection in immortalized cell lines of various animal species. Brain-, tissue culture-, and cell-free released viruses could all be neutralized with antibodies from naturally and experimentally infected animals (horse; hamster, rat, rabbit, mouse, and chicken), with highest titres in birds. Splenectomized rabbits, which were subsequently infected with BDV, efficiently produced high titres of neutralizing antibodies. All of the neutralizing sera and cerebrospinal fluids from infected animals inhibited tissue culture spread of BDV. Experimental infection and hyperimmunization induced antibodies directed against the major components of the soluble antigen (60, 40/38, 25 and 14.5 kD proteins). Analysis of the s-antigen complex with these sera and 6 stable monoclonal antibodies revealed that it consists of 40/38 and 25 kD proteins. Although each of these antibodies detected intracellular virus-specific structures they did not recognize outer plasma membrane antigens, showed no cross-reactivity, and had no neutralizing capacity. Unifying pathogenetic concepts of this neurotropic virus and its structural elements are discussed.

Animals↗
PubMed1993

Modification of Cys-128 of pig kidney fructose 1,6-bisphosphatase with different thiol reagents: size dependent effect on the substrate and fructose-2,6-bisphosphate interaction.

Treatment of fructose 1,6-bisphosphatase with N-ethylmaleimide was shown to abolish the inhibition by fructose 2,6-bisphosphate, which also protected the enzyme against this chemical modification [Reyes, A., Burgos, M. E., Hubert, E., and Slebe, J. C. (1987), J. Biol. Chem. 262, 8451-8454]. On the basis of these results, it was suggested that a single reactive sulfhydryl group was essential for the inhibition. We have isolated a peptide bearing the N-ethylmaleimide target site and the modified residue has been identified as cysteine-128. We have further examined the reactivity of this group and demonstrated that when reagents with bulky groups are used to modify the protein at the reactive sulfhydryl [e.g., N-ethylmaleimide or 5,5'-dithiobis-(2-nitrobenzoate)], most of the fructose 2,6-bisphosphate inhibition potential is lost. However, there is only partial or no loss of inhibition when smaller groups (e.g., cyanate or cyanide) are introduced. Kinetic and ultraviolet difference spectroscopy-binding studies show that the treatment of fructose 1,6-bisphosphatase with N-ethylmaleimide causes a considerable reduction in the affinity of the enzyme for fructose 2,6-bisphosphate while affinity for fructose 1,6-bisphosphate does not change. We can conclude that modification of this reactive sulfhydryl affects the enzyme sensitivity to fructose 2,6-bisphosphate inhibition by sterically interfering with the binding of this sugar bisphosphate, although this residue does not seem to be essential for the inhibition to occur. The results also suggest that fructose 1,6-bisphosphate and fructose 2,6-bisphosphate may interact with the enzyme in a different way.

Amino Acids↗
PubMed1993

Structure, function, and intracellular localization of glycoprotein B of herpesvirus simian agent 8 expressed in insect and mammalian cells.

The cloned gene of glycoprotein B (gB) of herpesvirus simian agent 8 (SA 8) was expressed with a baculovirus system in insect cells. Expression of gB was easily detectable over the cellular background by Coomassie staining of electrophoretically separated proteins. Endoglycosidase digestion of immunoprecipitated gB revealed that the gene product is N-glycosylated, but only with unprocessed, endoglycosidase-H sensitive carbohydrates. The lack of terminal glycosylation of gB is consistent with the observation that gB expressed in insect cells has a molecular weight slightly lower than gB synthesized during an SA 8 infection in mammalian cells. The truncated carbohydrates of gB from insect cells have no measurable effect on the tertiary structure of gB. Immunofluorescence studies on mammalian cells expressing gB from a simian virus 40 based vector revealed that the glycoprotein is localized to cytoplasmic membranes, to the plasma membrane and to the nuclear envelope. Cells expressing gB were fused to polykaryons, which shows that gB has cell fusing activity in the absence of any other SA 8 gene product.

Animals↗
PubMed1993

Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors.

BACKGROUND: Neoplasias, especially in their more advanced stages, are often associated with chronic anemia of malignancy which impairs the patient's physical ability and quality of life. PATIENTS AND METHODS: Forty-two patients with chronic anemia associated with hematological malignancies (18 multiple myelomas, 10 myelodysplastic syndromes) or solid tumors (9 breast cancers, 5 colon cancers) were treated with 150-300 units/kg rHuEPO for a median time period of 16 weeks. Response was defined as an increase of the initial hemoglobin level by at least 2 g/dl. RESULTS: The response rates for solid tumors were comparable (44.4% and 40% for breast cancer and colon cancer, respectively), whilst the response in patients with hematological malignancies depended strongly on the disease entity (77.8% for multiple myeloma, 10% for myelodysplastic syndrome). Pretreatment serum levels of endogenous erythropoietin (EPO) were significantly higher in non-responding patients than in responders. During rHuEPO therapy, EPO levels in non-responders increased even further, while they remained basically unchanged in responding patients. In responders, the WHO performance status before the start of rHuEPO therapy was more favorable and showed impressive improvement during the course of treatment. The median survival time of responders was 28.0 months as compared to only 9.2 months for non-responders. Clinical symptoms of anemia subsided or at least considerably improved under successful rHuEPO therapy. With the exception of occasional flu-like symptoms, no undesirable effects of rHuEPO treatment were observed. CONCLUSIONS: In conclusion, rHuEPO treatment corrected anemia of malignancy both in patients with hematologic disease and in those with solid tumors, but responsiveness varied considerably amongst the different disease entities.

Aged↗
PubMed1993

Immunophenotypic characterization of myelomonocytic cells in patients with myelodysplastic syndrome.

Infections, an important determining factor in the clinical course of myelodysplastic syndromes (MDS), result in activation of myelomonocytic cells. In this study we demonstrate activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes observed in two groups of MDS patients, one with low and another one with high clinical risk, and compared them to healthy individuals. Significantly changed expression of the complement receptors 1 (CD35) and 3 (CD11b), the Fc gamma receptor I (CD64), the leucocyte-homing receptor (CD44) and the activation associated membrane proteins CD67 and M5 were found on monocytes and/or granulocytes of MDS patients. In low-risk MDS patients we observed activation-associated phenotypic changes only in monocytes, whereas in high-risk MDS patients, both monocytes and granulocytes showed such changes. Additionally, we performed respiratory burst experiments and observed an impaired response of monocytes and granulocytes derived from MDS patients. Despite the fact that all patients were free of infection by clinical criteria, cell surface phenotyping as well as the reduced respiratory burst capacity of myelomonocytic cells suggests in vivo preactivation of these cells.

Antigens, CD↗
PubMed1993

In borna disease virus infected rabbit neurons 100 nm particle structures accumulate at areas of Joest-Degen inclusion bodies.

Borna disease virus infected rabbits were chosen to search for electronmicroscopic structures. Intensively investigated hippocampal neurons showed intranuclear inclusions; 100 nm particle-like structures surrounded by 20 nm granular forms were prominent. In connection with elsewhere reported in situ hybridization studies of virus-specific RNA to areas of the Joest-Degen inclusions we suggest that these particle structures may represent Borna virus. Jost-Degen (8) found intranuclear inclusion bodies in neurons to be pathognomonic for Borna disease (BD) in the horse. Half a century later these structures were suggested to represent BD virus (BDV)-specific antigen aggregates (15). A century later we characterized the virus to contain a single and negative stranded RNA of 8.5 kb, which transcribes in the nucleus (5) and could show that virus complementary RNA seems to hybridize spot-like to nuclear areas, probably representing the Jost-Degen inclusions (7). Electron microscopic (EM) findings on structures in BDV infected brain cells and about particle-like structures obtained from infected tissue culture cells have been reported by different groups (1, 2, 3, 4, 5, 6, 9, 11, 12, 13). The demonstration of crystalline aggregates and filament bundles in the cytoplasma and karyospheridia (nuclear bodies) were prominent. Such structures were seen in infected rabbits, hamsters, rats mice and naturally infected horses. The phenotypic description of filamentous structures, crystalline aggregates in the cytoplasma and large karyospheridia were prominent. Based on our experience with BDV infections in rabbits we selected this species for ultrastructural studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗