Biomedical subjects

J Lehmann

Publications and source records attributed to J Lehmann.

At least 55 records · Page 3Linked to original sources

PubMed2001

[After-care of bladder carcinoma].

The present article offers an introduction to the aftercare of patients with carcinoma of the urinary bladder. These recommendations are based on the guidelines of the German Association of Urology and the European Association of Urology. Aftercare always depends on the risk of recurrence and progression of the primary tumor and the extent of the therapy applied. Thus, after transurethral resection of a superficial carcinoma of the urinary bladder, aftercare focuses on follow-up cystoscopy. Radical cystectomy of the muscle-invading and locally advanced carcinoma should be followed by extensive examinations, including computed tomography of the pelvis and the abdomen. In addition, the various forms of urinary diversion after cystectomy with its specific late complications should be included in the aftercare. Moreover, the psychological significance of the follow-up examinations should not be neglected.

Aftercare↗

PubMed2001

Enantioseparation of linear and cyclic chiral bis(phenethyl)amines by means of cyclodextrin-modified capillary electrophoresis.

For two years drugs introduced to the market have had- to be enantiomerically pure. Rapid and cheap methods of high reproducibility must, therefore, be available for evaluation of enantiomeric purity. Within the framework of a larger project dealing with chiral recognition of phenethylamines by means of native and derivatized cyclodextrins it was intended to find capillary electrophoresis methods suitable for separation of the enantiomers of chiral bis(phenethyl)amines and their corresponding cyclic analogues, within 10 min, using small amounts of a chiral selector, to save time and money. Heptakis(2,3-O-diacetyl-6-sulfato)beta-CD was found to be the most promising candidate most often fulfilling these requirements.

Cyclodextrins↗

PubMed2001

Growth and differentiation of permanent and secondary mouse myogenic cell lines on microcarriers.

Myogenesis involves the determination of progenitor cells to myoblasts, their fusion to yield multinuclear myotubes, and the maturation of myotubes to muscle fibres. This development is reflected in a time pattern of gene expression, e.g. of genes coding for desmin, the myogenic factors myogenin and myoD, the acetylcholine receptor alpha-subunit and the muscular chloride channel CIC-1. We attempted to improve yields and myogenic differentiation in culture by using three-dimensional microcarrier systems. Out of a variety of carriers tested in stationary cultures, collagen-coated dextran Cytodex3 beads proved optimal for the proliferation and differentiation of the murine myogenic cell line C2C12. With C2C12 myoblasts in stationary and stirred systems (Spinner- and SuperSpinner flasks), surface adherence, differentiation into myotubes and expression of muscle-specific mRNAs on Cytodex3 beads were the same as in conventional cultures. Other carriers tested (DEAE cellulose, glass, plastic, cellulose, polyester) did not support growth and differentiation of C2C12 cells. The secondary mouse myogenic stem cells M12 and M2.7-MDX proliferated and differentiated well in stationary Cytodex3 cultures, but no differentiation occurred in Spinner flasks. As indicated by light and scanning electron microscopy, C2C12 myotubes formed not only on but also in between Cytodex beads. The secondary cell lines may succumb to shear forces under these conditions.

Actins↗

PubMed2001

The role of adjuvant chemotherapy for locally advanced bladder cancer.

The incidence of locally advanced bladder cancer is estimated at 5 new cases per 100,000 of the population annually in North America and most European countries. Radical cystectomy for muscle-invasive organ-confined tumors and locally advanced disease, which is defined as extravesical tumor growth or involvement of regional lymph nodes, is the preferred treatment in Japan, the United States, and in some countries of Europe. The clinical outcome of radical cystectomy has improved remarkably over the past 20 years as a result of advances in operative technique and perioperative care. Nevertheless, at least 50% of patients with invasive bladder cancer are expected to develop progressive disease within the first 2 years when treated with radical cystectomy alone. In order to improve the fate of muscle-invasive and locally advanced disease, the administration of additional therapy to definite treatment has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy as well as combined radio-chemotherapy. Prolonged progression-free survival for patients suffering from locally advanced bladder cancer by administration of adjuvant systemic chemotherapy has been suggested by three randomized studies, published by Skinner, Freiha and Stöckle since 1991. These studies demonstrated a disease-free survival benefit of 17-50% within the first 3-5 years when applying adjuvant systemic chemotherapy after radical cystectomy. Patients who most likely benefit from adjuvant chemotherapy are those with limited node-positive disease, extravesical tumor, and direct invasion into adjacent viscera, such as prostate, uterus, or vagina. This review will summarize past, current, and future aspects of systemic adjuvant chemotherapy for transitional cell carcinoma of the bladder.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Prostate-specific antigen in female urine: a prospective study involving 217 women.

OBJECTIVES: Histomorphologic studies have provided evidence of prostate-specific antigen (PSA)-producing tissue in the female urethra. Some urine samples from women in a small series were positive for PSA, but no systematic investigation of this subject has been done to date. METHODS: In a prospective study, we analyzed whether PSA occurs in the urine of women and what factors induce detectable PSA levels. The urine samples of 217 women were analyzed (Hybritech-Tandem E-PSA) under standardized conditions. The impact of urine pH and volume was investigated, and the results were correlated with clinical data (age, residual urine, urinary tract infection and prior sexual intercourse within 48 hours). RESULTS: A positive PSA level greater than the detection limit of 0.1 ng/mL was found in 11% of the analyzed samples; their mean value was 0.29 ng/mL. pH correction did not result in a significant difference. The voiding volume had no influence on the PSA level. Among the cases of detectable PSA, women younger than 50 years of age (n = 14) had a mean PSA of 0.34 ng/mL and those older than 50 years (n = 9) a mean of 0.23 ng/mL. One of 9 women with and 22 of 208 women without residual urine volume had a detectable PSA level, as did 0 of 20 with and 23 of 197 women without urinary tract infection, and 3 of 7 with and 20 of 210 women without prior sexual intercourse within the previous 48 hours. None of the differences were significant. CONCLUSIONS: A urine PSA level was detected in 11% of all women studied, with PSA values apparently age dependent. Any urine portion is suitable for analysis. No influence was determined for residual urine volume or urinary tract infection. Sexual intercourse may cause detectable PSA values, but the data of this study did not provide sufficient evidence for this hypothesis.

Adult↗

PubMed2001

Capture of proteins from mammalian cells in pilot scale using different STREAMLINE adsorbents.

This presentation compares three different expanded bed matrices. STREAMLINE rProtein A, STREAMLINE SP-XL and STREAMLINE Chelating were monitored in respect to their ability to clarify the broth, to concentrate and to purify the distinct target protein. The capture of a mouse IgG1 and a recombinant prothrombin (PT) was carried out in pilot scale using a 100-l bioreactor and STREAMLINE 100 and 200 columns, respectively. The robustness of the process was also estimated monitoring the expansion behaviour and the cell and debris concentrations during the load and in the eluat. In all cases the capture of the target proteins was comparable to conventional chromatographic systems. The purification success was mainly dependent on the selectivity of the ligand used. The affinity process resulted in a highly purified product. The ion exchanger and chelating material mainly concentrated the product. In all three cases 100 l of cell broth were successfully processed in one run. The robustness of the ion exchanger process was poor, because of strong cell matrix interaction. However, for the chelating and especially for the affinity matrix a highly reproducible process was obtained.

Adsorption↗

PubMed2001

Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for the detection of circulating tumor cells in peripheral blood and bone marrow of bladder cancer patients.

OBJECTIVES: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The ability to detect circulating tumor cells in peripheral blood or bone marrow could be of prognostic value for the disease with the consequence of early adjuvant chemotherapy. We established a sensitive and specific method using a double cytokeratin-20 (CK-20) reverse-transcriptase polymerase chain reaction (RT-PCR) to detect circulating bladder cancer cells in venous blood and bone marrow MATERIAL AND METHODS: The sensitivity of the detection method was determined by a serial dilution of bladder cancer cells from the cell line HT1376 in whole blood. Bone marrow from 20 bladder cancer patients was drawn prior to radical cystectomy and CK-20 cDNA was amplified by RT-PCR. Additionally, pre- and postoperative venous blood samples from 11 of these patients with bone marrow aspirates and 9 patients undergoing only transurethral resection of the bladder as well as blood samples of 25 healthy volunteers were investigated by CK-20 RT-PCR. RESULTS: The detection limit of the method was 2 bladder cancer cells/ml whole blood containing one million peripheral blood mononuclear cells. The positive detection rate in bone marrow was 7 of 20 (35%) for bladder cancer patients of all stages. However, investigation of the preoperatively collected venous blood samples from 20 patients revealed onyl 2 positive findings, belonging to advanced tumor stages pT4pN0M0 and pT3pN2M0. In contrast, CK-20 was detected in 3 of 20 postoperatively collected venous blood samples from patients with low tumor stages (pTaNXM0 and pT1NXM0) as well as from 1 patient with pelvic lymph node metastases (pT3apN2M0). All venous blood samples of the control group (n = 25) were negative for CK-20. CONCLUSION: The detection of circulating bladder tumor cells in venous blood and bone marrow by the CK-20 RT-PCR is a promising approach that could improve risk assessment and the identification of bladder cancer patients who would benefit from adjuvant chemotherapy.

Adult↗

PubMed2001

[Continuously perfused cultivation of genetically-engineered CHO cells producing prothrombin in a modified Super-Spinner].

A Super-Spinner was Modified by mounting a stainless steel filter(pore size 75 microns) to the impeller shaft to retain cells while fresh nutrient is perfused. Using Macroporous microcarrier Cytopore 1, continuously perfused cultivation of a recombinant CHO cell line, CHO2DS producing prothrombin was performed with the perfusion of a protein-free medium DF6S. The cell retention rate was more than 90% during the 24 days continuously perfused cultivation. The viable cell density of CHO2DS and prothrombin concentration reached 4.62 x 10(6)(cells.m/L) and 11.3(mg/L) respectively after 9 days culture.

Animals↗

PubMed2001

Detection of natural peptide antibiotics in human nasolacrimal ducts.

PURPOSE: To determine the expression and production of antimicrobial peptides by mucosal cells of the lacrimal passage in healthy and pathologic states. METHODS: Detection of bactericidal-permeability-increasing protein (BPI), heparin-binding protein (CAP37), human cationic antimicrobial protein (LL-37), human alpha-defensin 5 (HD5), human alpha-defensin 6 (HD6), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was performed by reverse transcription-polymerase chain reaction (RT-PCR). Intracellular deposition of lysozyme, lactoferrin, secretory phospholipase A(2), human neutrophil defensins (HNP-1, -2, and -3), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was analyzed immunohistochemically. Samples were obtained from 15 patients by surgery and from 10 cadavers. RESULTS: RT-PCR revealed BPI, CAP37, and HBD-1 mRNA in samples of healthy nasolacrimal duct epithelium. Additionally, HBD-2 mRNA was detected in epithelial samples from patients with dacryocystitis. Messenger RNAs for LL-37 and alpha-defensin 5 and 6 were absent in all samples investigated. Immunohistochemistry revealed lysozyme, lactoferrin, secretory phospholipase A(2), and HNP-1, -2, and -3 to be present in all samples, whereas HBD-1 was present only in some of the healthy and inflamed samples. Immunoreactive HBD-2 peptide was visible only in some of the inflamed samples. CONCLUSIONS: The data suggest that the human efferent tear ducts produce a broad spectrum of antimicrobial peptides. Under inflammatory conditions, changes in the expression pattern occurred, revealing induction of the human inducible defensin HBD-2 and in some cases downregulation of HBD-1 and CAP37. Antimicrobial peptides have a therapeutic potential in dacryocystitis, in that they have a broad spectrum of antimicrobial activity and accelerate epithelial healing. However, caution is appropriate, because defensins also promote fibrin formation and cell proliferation, which are key elements in scarring processes, such as dacryostenosis.

Adolescent↗

PubMed2000

Surface plasmon dynamics in silver nanoparticles studied by femtosecond time-resolved photoemission.

Multiphoton photoelectron spectroscopy reveals the multiple excitation of the surface plasmon in silver nanoparticles on graphite. Resonant excitation of the surface plasmon with 400 nm femtosecond radiation allows one to distinguish between photoemission from the nanoparticles and the substrate. Two different previously unobserved decay channels of the collective excitation have been identified, namely, decay into one or several single-particle excitations.

Journal Article↗

PubMed2000

Long term follow-up of combined radiochemotherapy for locally advanced bladder carcinoma.

BACKGROUND: The 5- and 10-year survival rates and the toxicity of combined radiochemotherapy for 53 consecutive patients with locally advanced bladder carcinoma were studied in a noncomparative trial. METHODS: Between November 1986 and October 1987, 53 consecutive patients (mean age, 68 years) with muscle invasive and/or locally advanced bladder carcinoma were treated by simultaneous chemotherapy and hyperfractionated irradiation. Radiation was administered during the first to fourth week and during the ninth to tenth week as an interrupted treatment protocol. Cisplatin and epirubicin were used as radiosensitizers before radiation. The maximum dose of irradiation was 57.6 grays. RESULTS: Of 53 patients, 45 completed the planned treatment course. Causes for discontinuing therapy in 8 patients were pronounced myelosuppression (n = 2), severe gastrointestinal symptoms (n = 2), nephrotoxicity (n = 1), and severe radioproctitis (n = 1). Two additional patients stopped therapy due to vascular diseases independent of treatment-related toxicity. The overall survival for all 53 patients was 23% after 5 years and 8% after 10 years. Cause specific survival was 36% after 5 years and 29% after 10 years. Four patients are still alive after 10 years without disease progression. One of them received incomplete therapy due to toxicity. All four patients underwent transurethral resections for superficial, local tumor recurrences. CONCLUSIONS: The poor prognosis group of patients with invasive and/or locally advanced bladder carcinoma was found to have a limited disease specific survival after combined radiochemotherapy.

Adult↗

PubMed2000

7-Methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine: a new heterocyclic system and a new lead compound for dopamine receptor antagonists.

Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2, 3-g]azecine (LE 300) proved to be of high affinity for the D(1) binding site (K(i) = 0.08 nmol for displacement of [(3)H]SCH23390), being superior in this assay to standards such as butaclamol and SCH23390. This compound was characterized as a dopamine antagonist by conditioned avoidance response test with mice. Thus, LE 300 represents the lead of a new class of dopamine antagonists for future investigations.

Animals↗

PubMed2000

Cultivation of immortalized human hepatocytes HepZ on macroporous CultiSpher G microcarriers.

Cultivation of the new immortalized hepatocyte cell line HepZ was performed with a 1:1 mixture of DMEM and Ham's F12 media containing 5% FCS. The cells were grown in their 40th passage in 100 mL and 1 L volumes in spinner flasks and in a bioreactor, respectively. For the production of adherently growing HepZ cells macroporous CultiSpher G gelatin microcarriers were used in various concentrations from 1 to 3 g/L. The cells were seeded in a density of 2 x 10(5) cells/mL when using a microcarrier concentration of 1 g/L and 5 x 10(5) cells/mL at a microcarrier concentration of 3 g/L. After 7 days of cultivation a maximum cell concentration of 4.5 x 10(6) cells/mL was obtained in the spinner culture using a microcarrier concentration of 1 g/L. With bubble-free aeration and daily medium exchange from day 7, 7.1 x 10(6) cells/mL were achieved in the bioreactor using a microcarrier concentration of 3 g/L. The cells exhibited a maximum specific growth rate of 0.84 per day in the spinner system and 1.0 per day in the bioreactor, respectively. During the growth phase the lactate dehydrogenase (LDH) activity rose slightly up to values of 200 U/L. At the end of cultivation the macroporous carriers were completely filled with cells exhibiting a spherical morphology whereas the hepatocytes on the outer surface were flat-shaped. Concerning their metabolic activity the cells predominantly consumed glutamine and glucose. During the growth phase lactate was produced up to 19.3 mM in the spinner culture and up to 9.1 mM in the bioreactor. Maximal oxygen consumption was 1950 nmol/(10(6) cells. day). HepZ cells resisted a 4-day long chilling period at 9.5 degrees C. The cytochrome P450 system was challenged with a pulse of 7 microgram/mL lidocaine at a cell density of 4.5 x 10(6) cells/mL. Five ng/mL monoethylglycinexylidide (MEGX) was generated within 1 day without phenobarbital induction compared to 26 ng/mL after a preceded three day induction period with 50 microgram/mL of phenobarbital indicating hepatic potency. Thus, the new immortalized HepZ cell line, exhibiting primary metabolic functions and appropriate for a mass cell cultivation, suggests its application for a bioartificial liver support system.

Amino Acids, Branched-Chain↗

PubMed2000

Surmounting oscillating barriers

Thermally activated escape over a potential barrier in the presence of periodic driving is considered. By means of novel time-dependent path-integral methods we derive asymptotically exact weak-noise expressions for both the instantaneous and the time-averaged escape rate. The agreement with accurate numerical results is excellent over a wide range of driving strengths and driving frequencies.

Journal Article↗

PubMed2000

Physico-chemical constraints connected with the coding properties of the genetic system.

New insights on the origin of the genetic code, based on the analysis of the physico-chemical properties of its molecular constituents (RNA and amino acids), are reported in this paper. We point out a symmetry in the genetic code table and show that it can be explained by the nature of the anticodon-codon interaction. The importance of the strength of this interaction is examined and a correlation is found between the free-energy change (DeltaG(0)) of anticodon-codon association and the volume of the corresponding amino acids. This correlation is investigated in conjunction with the well-known one linking the hydrophobicity of the anticodons with that of the amino acids. We show that they can be considerated separately and that the energy vs. volume correlation may be explained by the process implicating the peptide bond formation between two successive amino acids during translation. This interpretation is supported by a statistical pattern of bases (purines or pyrimidines), observed in present coding genes, and by considerations involving the availability of the different kinds of amino acids. Finally, we try to explain the hydrophobicity correlation when reconstructing the events at the time of the so-called "RNA World". The whole of our investigation shows that the genetic code might be sufficiently robust to exist without the participation of pre-existing proteins, and that this robustness is a consequence of the physico-chemical properties of the four bases of the genetic system.

Amino Acids↗

PubMed2000

Lack of effect of an early stressful life event on sensorimotor gating in adult rats.

Hypotheses of the etiology of schizophrenia emphasize the important role of perinatal insults in predisposing individuals to the development of the disease, so that an animal model in which a discrete postnatal manipulation of the infant social environment yields schizophrenia-like behavior in adulthood would be valuable in terms of the study of the neural substrate and treatment of schizophrenia. Schizophrenics demonstrate a deficit in sensorimotor gating (prepulse inhibition), and a similar phenomenon has been described in adult rats following the administration of direct and indirect dopamine agonists. Recently it has been reported that a 24 h separation of rat pups from the mother results in a disruption of prepulse inhibition at adulthood. Here we report a study which investigated the same phenomenon but which, in contrast to the previous study, utilized unrelated subjects all derived from different dams. Maternal separation was conducted for 24 h with pups aged 4, 9 or 18 days and these subjects, together with non-separated controls, were tested at age 3 months in terms of their prepulse inhibition in the acoustic startle response paradigm. Maternal separation did not disrupt prepulse inhibition. Comparison of males and females (with a maximum of one opposite-sex sibling) demonstrated that acoustic startle response and prepulse inhibition of this response was enhanced in males relative to females. This study indicates that 24 h maternal separation does not provide a robust model for studying the effects of early environmental insults on the long-term abnormal development of sensorimotor gating.

Acoustic Stimulation↗

PubMed2000

Acute brachial artery thrombosis as the initial manifestation of human immunodeficiency virus infection.

Thrombosis of upper extremity arteries is most commonly due to atherosclerosis of the proximal subclavian artery, trauma, or catheter-related injury. In the absence of an identifiable cause, a search for a hypercoagulable state is indicated. Hematologic manifestations of human immunodeficiency virus (HIV) infection and AIDS are frequent occurrences (Coyle TE. Med Clin N Am 1997;81:449-476). The most important of these are cytopenias (anemia, neutropenia, and thrombocytopenia). The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. In addition, various coagulation abnormalities have been reported in HIV-infected patients. Apart from thrombocytopenia, these have included a prolonged APTT due to the presence of lupus anticoagulant, an increased prevalence of protein S and heparin cofactor II deficiency, and hypoalbuminemia-related fibrin polymerization defects (Toulon P. Ann Bio Clin (Paris) 1998;56:153-160). HIV infection has also been associated with endothelial dysfunction. Although for the most part asymptomatic, elevated D-dimer levels have been found in HIV-infected patients, suggesting the existence of a prethrombotic state. In fact, clinical thrombosis eventuates in 2% of these patients (Toulon, 1988). Documented thromboses have involved both veins and arteries. We hereby present a patient who developed an acute thrombosis of his brachial artery as the initial manifestation of HIV infection.

Acute Disease↗

PubMed2000

Grafting of fibroblasts isolated from the synovial membrane of rheumatoid arthritis (RA) patients induces chronic arthritis in SCID mice-A novel model for studying the arthritogenic role of RA fibroblasts in vivo.

The objective of this study was to verify whether isolated rheumatoid arthritis (RA) synovial fibroblasts induce chronic arthritis in SCID mice, in analogy to whole tissue pieces. Fibroblasts were isolated from the synovial membrane of four RA patients (or controls) by out-growth and repeated-passage culture. Following flow-cytometry characterization, 2x10(6)cells were transferred into the left knee joint of SCID mice. The development of arthritis was assessed by joint swelling and histological changes. Human and murine cytokines were measured in vitro in co-cultures (or Transwelltrade mark systems) of human and murine cells. Purified RA synovial fibroblasts, but not healthy synovial or skin fibroblasts, induced hu/mu arthritis within 6 weeks. In-vitro secretion of murine and human interleukin(IL)-6, as well as murine tumour necrosis factor (TNF)-alpha, indicated cross-activation between murine macrophages and human RA fibroblasts. Soluble-factor mechanisms proved more effective than cell-contact mechanisms. Purified RA fibroblasts can, alone, induce hu/mu SCID arthritis. The cytokine profile suggests that xenogeneic interaction between human fibroblasts and murine macrophages may determine the sequence of events leading to hu/mu arthritis.

Animals↗