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Biomedical subjects

F Geissler

Publications and source records attributed to F Geissler.

36 records · Page 2Linked to original sources
PubMed1998

[Intra-abdominal abscess].

In more than 80% of cases, intra-abdominal abscesses derive from an intra-abdominal organ, and in most cases they develop after operative procedures. Regarding anatomy, intra-abdominal abscesses can be divided into intra-peritoneal and visceral abscesses and those located in the anterior retroperitoneal space. Despite improvements in ultrasonography, CT is still the most effective method in diagnosis and therapy. Percutaneous ultrasound or CT-guided drainage is a therapy characterized by low procedural morbidity and is successful in 80% of cases if strict criteria are met. Complicated abscesses and those cases in which the underlying disease has to be treated require surgical intervention. Most liver abscesses are treated interventionally; in abscesses of the pancreas or spleen and in Crohn's disease, surgery is necessary. The combination with sufficient antibiotic drug therapy is very important. Specific infectious diseases appearing as intra-abdominal conglomerates (tuberculosis, actinomycosis, amebiasis) lead to a delay in diagnostics because of their scarcity and are characterized by special patho-anatomical, diagnostic and therapeutic features. The crucial thing is to take a specific infection into consideration.

Abdominal Abscess↗
PubMed1994

[The chemoembolization of hepatocellular carcinoma: the computed tomographic findings and clinical results in prospective repetitive therapy].

Between April 1989 and March 1993 162 transarterial chemoembolizations (TACE) were performed repeatedly (mean interval: 2.9 months) in 52 patients with hepatocellular carcinoma (HCC): An emulsion of Lipiodol and epirubicin was injected as selectively as possible in a dosage proportional to liver function and tumour size. Before and after each TACE the size of tumours and ratio of tumour volume containing Lipiodol (RTVCL) were determined in CT and the grade of tumour vascularisation was assessed angiographically. The RTVCL increased from 58% after the first treatment to 73% after the third treatment. RTVCL and Lipiodol retention were higher in responders than in non-responders. Tumours with expansive growth pattern showed a higher response rate (56%) than infiltrating tumours (20%). Mean survival of these patients was different (19 and 8 months; p < 0.01), respectively. Survival rates of all patients were 54, 22, and 11% after 1, 2 and 3 years, respectively. Repeated TACE shows local effectiveness. Three treatments during a period of one year are recommended for patients with Child-Pugh class A cirrhosis.

Adult↗
PubMed1992

Intracellular catabolism of radiolabeled anti-mu antibodies by malignant B-cells.

The endocytosis and degradation of 125I-labeled anti-mu monoclonal antibody DA4-4 by a Burkitt's lymphoma cell line was investigated using biochemical, chromatographic, electrophoretic, radioautographic, and electron microscopic techniques. 125I-DA4-4 was rapidly internalized by Ramos cells and routed from endosomes to lysosomes. Proteolysis of radiolabeled antibodies began in a late endosomal compartment, but lysosomes were primarily responsible for the terminal degradation of 125I-DA4-4. Catabolism of 125I-DA4-4 could be inhibited by 74-95% by blocking its delivery to late endosomes and lysosomes by incubation at 18 degrees C, by neutralizing the pH in intracellular organelles with monensin or ammonium chloride, or by inhibiting lysosomal enzymes with leupeptin. Radiolabeled antibodies synthesized using the chloramine T or Iodo-Gen techniques were degraded three times faster than conjugates made using a nonmetabolizable 125I-tyramine cellobiose adduct. Five major intermediate metabolites (Mr 48,000, 42,000, 25,000, 15,000, and 10,000) were generated during the intracellular catabolism of 125I-DA4-4, but 125I-tyrosine was responsible for 95% of the small-molecular-weight metabolites released by cells into the culture medium. We anticipate that a full comprehension of the catabolism of radiolabeled antibodies by tumor cells will make possible the development of clinical interventions which will enhance the retention of radioimmunoconjugates by hematologic malignancies and improve the efficacy of radioimmunotherapy.

Animals↗
PubMed1991

Intracellular catabolism of radiolabeled anti-CD3 antibodies by leukemic T cells.

The endocytosis and intracellular metabolism of radiolabeled anti-CD3 MoAb 64.1 by the malignant human T cell line HPB-ALL were studied using biochemical, morphological, electrophoretic, and chromatographic techniques. Biosynthetically labeled [3H]64.1 and externally radioiodinated 125I-64.1 were similarly internalized and degraded by tumor cells, with approximately 70% of the initially bound radioactivity being released to the culture supernatant as trichloroacetic acid-soluble radioactivity in the first 24 hr of culture. Radiolabeled 64.1 was routed from the cell membrane to endosomes where initial proteolysis began and finally to lysosomes where terminal catabolism to single amino acids occurred. SDS-PAGE demonstrated four major intracellular metabolite species (46, 25, 15, and less than 10 kDa). Thin-layer chromatography demonstrated that greater than 95% of the trichloroacetic acid-soluble radioactivity in culture supernatants was 125I-monoiodotyrosine, indicating that proteases, not deiodinases, were of primary importance in catabolism of 125I-64.1. In the presence of inhibitors of lysosomal function (leupeptin, monensin, and ammonium chloride), 125I-64.1 degradation was impeded, causing prolonged retention of radioactivity in the lysosomal compartment of cells. However, although the pace of catabolism was markedly diminished by these agents, no major changes in the sizes of intermediate metabolites generated were observed. Our results suggest that judicious administration of lysosomal inhibitors (e.g. chloroquine, verapamil, monensin) may significantly enhance retention of radioimmunoconjugates by lymphoid malignancies, improving radioimmunoscintigraphic and radioimmunotherapeutic efforts.

Ammonium Chloride↗
PubMed1990

Inhibition of catabolism of radiolabeled antibodies by tumor cells using lysosomotropic amines and carboxylic ionophores.

The rates of degradation of radioiodinated monoclonal antibodies (MoAbs) by malignant T- and B-lymphoid cells were studied in the presence and absence of a variety of pharmacological agents known to affect the intracellular metabolism of internalized ligands. 125I-MoAbs directed against the CD2, CD3, CD5, and anti-mu surface antigens underwent rapid endocytosis, followed by prompt degradation with release of greater than or equal to 50% of the initially bound radioactivity as free, trichloroacetic acid-soluble 125I within 24 h. Lysosomotropic amines (chloroquine, ammonium chloride, amantadine), carboxylic ionophores (monensin, nigericin), calcium channel blockers (verapamil), thionamides (propylthiouracil), lysosomal enzyme inhibitors (leupeptin), and colchicine all inhibited metabolism of radioiodinated MoAbs and enhanced retention of 125I-MoAbs by tumor cells. The most effective agents (e.g., monensin, nigericin) diminished the release of free 125I by greater than 90% and enhanced retention of radioactivity by greater than 300% at 24 h. Experiments with immunoperoxidase electron microscopy and Percoll gradient fractionation of organelles from disrupted cells suggested that high concentrations of monensin (10-20 microM) delayed transfer of 125I-MoAbs to lysosomes, but other mechanisms (e.g., pH neutralization) were operative at lower concentrations (1-3 microM). Clinical administration of these agents may enhance retention of radioimmunoconjugates by tumor cells, resulting in improved radioimmunoscintigraphy and radioimmunotherapy.

Acid Phosphatase↗
PubMed1988

Developmental toxicity of aflatoxin B1 in the rodent embryo in vitro: contribution of exogenous biotransformation systems to toxicity.

Aflatoxin B1 (AFB1) is a known carcinogen and developmental toxin in various species of mammals, birds, amphibians, and fish. AFB1 requires metabolic activation (biotransformation) to the 2,3-epoxide metabolite for carcinogenicity; however, it is unknown if biotransformation is a prerequisite for AFB1 embryotoxicity. Cultured day 10 rat embryos were exposed to AFB1 alone and AFB1 in the presence of cofactors and hepatic S9 fractions from adult male rats induced with either phenobarbital or 3-methylcholanthrene. Under these different culture conditions qualitatively similar patterns of malformation were seen in all embryos exposed to AFB1. At culture concentrations of 15 microM or greater, AFB1 produced abnormalities in neural tube development in a concentration-dependent manner. The presence of hepatic S9 fractions had no effect on the ability of AFB1 to produce dysmorphogenesis in vitro or on the spectrum of malformations elicited. However, the addition of hepatic S9 fractions did greatly enhance the embryolethality of AFB1. This enhancement was greater with phenobarbital- than 3-methylcholanthrene-preinduced hepatic S9 fractions. Our results suggest that separate chemical mediators may be responsible for the embryolethal and dysmorphogenic effects of AFB1 observed in day 10 rat embryos in vitro. We found that the embryolethality of AFB1, but not the dysmorphogenicity, could be greatly modulated by exogenous biotransformation.

Abnormalities, Drug-Induced↗
PubMed1987

Differences in the rotation spectra of mouse oocytes and zygotes.

Rotation spectra of mouse oocytes, zygotes and embryos in the two-cell stage under the influence of high-frequency rotating fields were studied. The characteristic frequency (fc1) of cells isolated from superovulated + mated mice is different from that of oocytes. This was attributed to an increase in the membrane resistance and, less probably, to a change in the zona pellucida conductivity. The rotation spectra can be used to differentiate between non-fertilized and fertilized eggs. A theoretical interpretation of the measured spectra and simulation of the changes caused by fertilization is given.

Animals↗
PubMed1987

Analogues and derivatives of tenoxicam. 1. Synthesis and antiinflammatory activity of analogues with different residues on the ring nitrogen and the amide nitrogen.

The synthesis of tenoxicam, 4-hydroxy-2-methyl-N-2-pyridyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxami de 1,1-dioxide (1e), and of the analogues with various residues on the ring nitrogen and the amide nitrogen is described. This new class of "oxicams" has pronounced antiinflammatory and analgesic properties. The very specific structure-activity relationship of isomeric and isosteric groups at the amide nitrogen has been evaluated. The substituent in position 2 also has a great influence on the pharmacological properties. Tenoxicam is presently undergoing clinical trials.

Animals↗
PubMed1985

Defective neutrophil and monocyte motility in patients with early onset periodontitis.

Several studies have documented suppressed polymorphonuclear neutrophil (PMN) chemotaxis in most patients with juvenile periodontitis. In contrast, data regarding PMN chemotaxis in patients with rapidly progressive periodontitis are very limited, and monocyte (MN) chemotaxis and random migration of PMNs or MNs from these patients have not been studied previously. Accordingly, we examined cell motility of PMNs and MNs from 27 patients with rapidly progressive periodontitis, 5 patients with juvenile periodontitis, and 37 normal control subjects by using a microchamber technique and the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) as the chemoattractant. As a group, PMNs and MNs from patients with rapidly progressive periodontitis manifested significantly enhanced random migration relative to control cells (P less than 0.001), suppressed directed migration (chemotaxis) at FMLP doses of 10(-9) and 10(-8) M (P less than 0.05), and enhanced directed migration at a dose of 10(-6) M FMLP (P less than 0.01). In contrast, PMNs from patients with juvenile periodontitis exhibited normal random migration, and directed migration was significantly suppressed at all doses of FMLP tested (P less than 0.05). An abnormality of either PMN or MN motility was observed in 26 of 27 patients with rapidly progressive periodontitis. Enhanced random migration was seen in PMNs in 63%, MNs in 39%, and both cell types in 26% of the patients. Suppressed chemotaxis was seen in PMNs in 85%, in MNs in 74%, and in both cell types in 69% of the patients. The prevalence and magnitude of abnormalities in motility were somewhat lower in treated than in untreated patients. Thus, most, if not all, of this subgroup of patients with early onset, highly destructive periodontitis have abnormalities in PMN or MN motility, and these defects may differ from those seen in cells from patients with the juvenile form of the disease.

Adolescent↗
PubMedDate not supplied

Gender difference in ifosfamide metabolism by human liver microsomes.

Pharmacokinetic gender-dependent differences in cytochrome P450-mediated drug metabolism, especially CYP3A4, and their clinical implications are increasingly apparent. CYP3A4 seems to be the most important CYP isoform in both bioactivation and N-dechloroethylation of the alkylating prodrug ifosfamide, but informations about possible gender-related differences are lacking. Therefore we compared in 10 male and 10 female liver microsomal preparations the contents and activities of specific isoenzymes, involved in both metabolic pathways, especially CYP3A4, further CYP2A6, CYP2C9 and CYP2B6 and measured the in vitro activities of these microsomes in the ifosfamide 4-hydroxylation and N-dechloroethylation using high-sensitive HPLC/MS and -UV detection methods. Statistically significant differences between male and female livers were found in the mean CYP3A4 contents and activities. These differences had no consequences on the ifosfamide 4-hydroxylation activities of liver microsomes in vitro. In contrast, in the ifosfamide N-dechloroethylation reaction we found a statistically significant difference between the liver microsomes of male and female patients (0.13 +/- 0.05 nmol/min nmol P450 vs. 0.28 +/- 0.13 nmol/min x nmolP450, respectively). In conclusion, we firstly demonstrated such gender-related difference in the ifosfamide N-dechloroethylation, which could result in a higher risk of partly severe neurotoxic side effects in female patients.

Adult↗