High-pressure phase of copper(I) iodide.
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Journal Article↗
Biomedical subjects
M Hofmann
Publications and source records attributed to M Hofmann.
Schwann cell tumors express characteristic patterns of CD44 splice variants.
Members of the CD44 family of cell surface hyaluronate-binding proteins have been implicated in cell migration, cell-matrix interactions and tumor progression. To determine whether these proteins might play a role in the normal functions of Schwann cells and in their tumorigenesis, we examined the patterns of CD44 expression in Schwann cells from rat peripheral nerve, rat Schwann cell tumor lines, and human schwannomas. Normal rat spinal nerves and primary Schwann cell cultures expressed standard CD44 (CD44s) but not alternatively spliced variant isoforms. In contrast, rat Schwann cell tumor lines expressed both CD44s and a number of variants, including proteins containing sequences encoded by exon v6. Furthermore, we found that these cell lines bind hyaluronate, and that their cell surface hyaluronate binding correlates with CD44 expression. All of the human schwannomas also expressed CD44 variants, especially epitopes encoded by exon v5, the border between v7 and v8, and v9-10. These data indicate that Schwann cells normally express CD44s, that Schwann cell tumors express both CD44s and particular variants of CD44, and that CD44s and possibly variants of CD44 are involved in hyaluronate recognition by Schwann cell tumors.
Alternative Splicing↗
Baculovirus expression and affinity purification of protein E2 of classical swine fever virus strain Alfort/187.
The genome region encoding the major envelope glycoprotein E2 (gp55) of the classical swine fever virus (CSFV) strain Alfort/187 was cloned and sequenced. The E2 gene, either with or without additional authentic 5'-terminal sequences coding for two variants of a putative signal sequence, was used to construct recombinant baculoviruses expressing the respective glycosylated and nonglycosylated E2 protein in insect cells. The signal sequences mediated glycosylation in insect cells, but no efficient secretion of the protein into the cell culture supernatant was observed. Six histidine residues introduced at the carboxy terminus of E2 allowed purification of E2 protein by Ni(2+)-chelate affinity chromatography. The proteins obtained were characterized and their immunological properties were compared by western blot analysis.
Amino Acid Sequence↗
Differential CD44 expression patterns in primary brain tumours and brain metastases.
Splicing variants of CD44 (CD44v) are increasingly recognised as metastasis-promoting factors in rodent and some human cancers. However, the frequency for CD44v expression in human cancers and their metastases and the status of CD44v expression in low or non-metastatic tumours is still uncertain. To address this issue, we investigated CD44 expression patterns in brain metastases (BMTs) spread from more than ten organs and five types of primary brain tumours (PBTs) by Northern blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemical analysis. The results demonstrated that all of the 56 PBTs examined express standard form of CD44 (CD44s) but none of them express CD44v. In contrast, 22 of 26 BMTs studied were found with CD44v expression. Our data thus present direct evidence of a general distribution of CD44 in BMTs but suggest that such expression is an extremely rare event in PBTs. Therefore, the presence or absence of CD44v expression may be related to high or low metastatic potential of human malignancies.
Adult↗
Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: a near-infrared spectroscopy study.
We used near-infrared spectroscopy (NIRS) to study noninvasively the influence of aging on changes in the local concentration of oxygenated hemoglobin ([HbO2]), reduced hemoglobin ([HbR]), and total hemoglobin ([HbT] = [HbR] + [HbO2]) during activation of brain function. Young subjects (n = 12; age, 28 +/- 4 years) performing calculation tasks showed an increase in [HbO2] [mean (arbitrary units) +/- SD, 2.36 +/- 1.07] and [HbT] (2.24 +/- 1.13) in the frontal cortex, while [HbR] (-0.11 +/- 0.48) decreased. Elderly subjects (n = 17; age, 52 +/- 10 years) showed a significantly lower mean increase (p < 0.05) in [HbO2] and [HbT] levels (1.21 +/- 1.38 and 0.72 +/- 1.41, respectively). Regression analysis supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2] (y = -0.241x + 20.062; r = -0.431, p < 0.05) as well as [HbT] (y = -0.346x + 22.496; r = -0.568, p < 0.05). We conclude that NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging.
Adult↗
Reduced beta-amyloid response in lymphocytes of patients with Alzheimer's disease.
The beta-amyloid peptide (beta A4) is a principal constituent of senile plaques and is thought to play a major role in the pathophysiology of Alzheimer's disease (AD). Although the mechanism of beta-A4 neurotoxicity is still a matter of debate, one of its effects might be a destabilization of cellular calcium homeostasis, thus promoting neuronal damage. The influence of the toxic fragment beta A25-35 on the mitogen-induced rise in the intracellular calcium concentration ([Ca2+]i) in lymphocytes of AD (n = 13) and depressive patients (n = 14) as well as in healthy controls was therefore investigated (n = 16). The results showed a significant increase in the mitogen-induced calcium signal with lymphocytes of healthy controls and depressive patients. This beta A25-35-induced amplification was significantly lower in AD patients as compared to healthy controls but not as compared to depressive patients. The results thus confirm a postulated decreased beta-amyloid sensitivity in AD lymphocytes. However, this effect might not be as pronounced or as specific as recently described by Eckert et al., (1993b).
Aged↗
Stopped Delta -matter source in heavy-ion collisions at 10 GeV/nucleon?
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Journal Article↗
Isolation of bovine viral diarrhea virus-like pestiviruses from roe deer (Capreolus capreolus).
Cytopathogenic pestiviruses were isolated from two seronegative free-ranging roe deer (Capreolus capreolus) from northern Germany (Schleswig-Holstein): an adult female and a young buck collected on 6 December 1990 and 26 July 1991, respectively. The two isolates were identified by polymerase chain reaction as pestiviruses. However, they were negative when primers specific for bovine virus diarrhea virus or classical swine fever virus were used, indicating that the two isolates might belong to a separate group of pestiviruses of wild ruminants different from BVDV.
Animals↗
[Computer-assisted individualized memory training in Alzheimer patients].
Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with two patients suffering from probable Alzheimer's disease who were trained with a new computer-based program recently developed by our research group. An everyday task of personal relevance to the patient was simulated and trained on a PC touch screen using personal photographs of the patient's surroundings and biography. The patient's training performance (time, mistakes, number of advices) improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training, signs of emotional activation and of a transfer of the trained skills into real situations.
Activities of Daily Living↗
[Persistent granulocytosis and hyperuricemia after a single G-CSF injection (Filgrastim) in treatment of chemotherapy-induced myelosuppression in metastatic breast carcinoma].
We report about a patient with metastatic breast cancer treated with chemotherapy regime (CMF), who developed a febril leukopenia as well as a hyperuricemia. A single subcutaneous application of 300 micrograms Filgrastim led to a severe overstimulation with leukocytosis of max. 50,000 for about 8 days and hyperuricemia.
Aged↗
[CD44 expression patterns in primary and secondary brain tumors].
We investigated CD44 expression patterns in five types of primary brain tumors and brain metastases from more than ten organs by Northern blot, reverse transcription/polymerase chain reaction (RT/PCR) and immunocytochemical analyses. The results demonstrated that all of 72 primary brain tumors examined express standard form of CD44 (CD44s) but none of them express CD44v. In contrast, 22 of 26 brain metastases studied were found to express CD44v. Our data not only present a direct evidence of a general distribution of CD44 in primary brain tumors but also suggest that such expression is an extremely rare event in primary brain tumors. We conclude that CD44v may be a candidate marker for the evaluation of malignant potential of the tumors and the prognosis of cancer patients.
Base Sequence↗
[Immunohistochemical characterization of CD44 molecules expressed in human brain metastases].
CD44v adhesion molecules have been known to be related with carcinogenesis and metastasis of some human cancers including brain metastases of various origin. In this study, we demonstrated further that CD44v expression in brain metastases is extremely heterogeneous. Generally, v5/v6 is homogeneously expressed in the cell populations, while up-regulated v7-v10 could be usually found in a proportion of tumor cells, especially those close to necrosis, at the tumor border and with strong tendency of invasiveness. Our data thus suggest that heterogeneous CD44v expression may be determined not only by intrinsic nature of the cells but also by the surrounding micro-environment. Expression of multiple isoforms of CD44v may confer metastatic cells certain unique abilities, allowing them to localize, then to form metastatic colony in the brain.
Adenocarcinoma↗
[The recanalization of chronic coronary artery occlusions: what factors influence success?].
Between January 1986 and June 1990, recanalization with guide-wire and balloon angioplasty (PTCA) was attempted in 509 patients (416 men, 93 women; mean age 57.5 +/- 9 years) with chronic coronary artery occlusions. The data recorded were analysed to determine the factors which influenced the outcome. The intervention was initially successful in 284 patients (55.8%; circumflex branch: 50%; right coronary artery: 52%; venous bypass graft: 50%; anterior interventricular branch: 64%). The success rate was markedly reduced if (1) the occlusion had persisted for more than 6 months (9.5%; P < 0.001); (2) occlusion had occurred at or after a vessel kink (28.5%; P < 0.001); (3) there had been no vessel "stump" (36%; P < 0.01) and (4) the occlusion was longer than 10 mm (40.7%; P < 0.05). The success-rate was higher if (1) intracoronary anastomoses were absent (61.2%); (2) occlusion had occurred in a straight vessel (62.6%); (3) there had been a vessel stump (64%); (4) the occlusion had persisted for less than 4 weeks (68.5%) and (5) the length of occlusion was < or = 10 mm (75.8%).-These data indicate that the success of PTCA after chronic coronary artery occlusion depended on the site of occlusion, its duration and length, absence of orthograde collaterals and the presence of a vessel stump. Knowing the extent of these factors helps in delineating the indications.
Aged↗
Lattice dynamics of SiC polytypes within the bond-charge model.
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Journal Article↗
Characterization of the essential yeast gene encoding N-acetylglucosamine-phosphate mutase.
A previously cloned gene of Saccharomyces cerevisiae, which complements the growth defect of a phosphoglucomutase (pgm1 delta/pgm2 delta) double deletion mutant on a pure galactose medium [Boles, E., Liebetrau, W., Hofmann, M. & Zimmermann, F. K. (1994) Eur. J. Biochem. 220, 83-96], was identified as the structural gene encoding N-acetylglucosamine-phosphate mutase. The complete nucleotide sequence of the gene, AGM1, and surrounding regions were determined. AGM1 codes for a predicted 62-kDa protein with 557 amino acids and is located on chromosome V adjacent to the known gene PRB1 encoding protease B. No extended nucleotide or amino acid sequence similarities could be found in the databases, except for a small region of amino acids with high similarity to the active-site consensus sequence of hexosephosphate mutases. Three putative pheromone-responsive elements have been identified in the upstream region of the AGM1 gene. The gene is essential for cell viability. An agm1 deletion mutant progresses through only approximately five cell cycles to form a 'string' of undivided cells with an abnormal cell morphology resembling glucosamine auxotrophic mutants. Expression of the AGM1 gene on a multi-copy plasmid led to a significantly increased N-acetylglucosamine-phosphate mutase activity. Unlike over-expression of the AGM1 gene in a pgm1/pgm2 double deletion mutant which could restore phosphoglucomutase activity, over-expression of the PGM2 gene encoding the major isoenzyme of phosphoglucomutase did not increase N-acetylglucosamine-phosphate-mutase activity and did not restore growth of agm1 deletion mutant cells. Our observations indicate that the different hexosephosphate mutases of S. cerevisiae have partially overlapping substrate specificities but, nevertheless, distinct physiological functions.
Amino Acid Sequence↗
A family of hexosephosphate mutases in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae PGM1 and PGM2 genes encoding two phosphoglucomutase isoenzymes have been isolated and sequenced. The derived protein sequences are closely related to one another and show distinct sequence similarities to the human and rabbit phosphoglucomutases, especially in the region supposed to constitute the active site. PGM1 and PGM2 are located on chromosomes XI and XIII, respectively, just upstream of the known genes YPK1 and YKR2 coding for a pair of closely related putative protein kinases. These observations suggest that an extended region of DNA arose by the process of gene duplication. Cells deleted for both, PGM1 and PGM2, could not grow on galactose. No residual phosphoglucomutase activity could be measured in crude extracts or in permeabilized cells of pgm1/2 double mutants. Unexpectedly, growth with glucose was not impaired and the mutant cells were still able to accumulate trehalose and glycogen, although at a reduced level. Two further genes could be isolated and characterized which when over-expressed on a multi-copy plasmid could restore growth on galactose of the pgm1/2 double deletion mutant. Multi-copy complementation was due to a sharply increased level of phosphoglucomutase activity. Partial sequencing and characterization of the two genes revealed one of them to be SEC53 encoding phosphomannomutase. No extended sequence similarities could be found in the databases for the second gene. However, part of the derived amino acid sequence contained a region of high similarity to the active-site consensus sequence of hexosephosphate mutases from different organism. Further investigations suggest that a complex network of mutases exist in yeast which interact and can partially substitute for each other.
Amino Acid Sequence↗
Evaluation of liquid chromatography coupled with high-field 1H NMR spectroscopy for drug metabolite detection and characterization: the identification of paracetamol metabolites in urine and bile.
The applicability of coupled reversed-phase high performance liquid chromatography (HPLC)-NMR spectroscopy for the detection and identification of paracetamol (N-(4-hydroxyphenyl)acetamide) and its sulfate, glucuronide and N-acetylcysteinyl metabolites in the unprocessed biological fluids, human urine, rat urine and rat bile, is investigated. Analysis of these samples was performed by gradient HPLC elution and directly coupled 500 MHz 1H NMR spectroscopy detection using a combination of one- and two-dimensional NMR methods in stopped-flow mode. The stopped-flow approach is demonstrated to be an efficient technique for identification of drug metabolites which have, for example, a UV-chromophore. Stopped-flow HPLC analysis with NMR detection is a viable technique and halting the chromatographic process several times during a run has a negligible effect on the separation and NMR characterization. The post-acquisition data processing method of 'quantified maximum entropy' is shown to provide a means of improving the quality of spectra for minor components, thus aiding NMR resonance assignments.
Acetaminophen↗
In vitro activity of immunoconjugates between cisplatin and an anti-CA125 monoclonal antibody on ovarian cancer cell lines.
Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic agent that is used in the treatment of ovarian cancer. However, the clinical use of CDDP is restricted by its severe side effects. In order to reduce these side effects and to enhance its therapeutic efficacy, we developed specific immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP, using diethylene triamine pentaacetic acid (DTPA) as a linker. The coupling efficiencies of the different preparations synthesized, varied between 1.10 +/- 0.42 and 2.65 +/- 1.60 mol of CDDP per mol of antibody protein. Despite the chemical modification of the antibody molecule, specific binding activity of the OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated by means of immunohisto-/cytochemical staining of frozen sections of ovarian cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell line NIH:OVCAR 3. The antiproliferative activity of the immunoconjugates was tested against the human ovarian cancer cell lines NIH:OVCAR 3 and SKOV 3, applying a kinetic crystal violet microassay. Despite the promising results obtained with the specific immunostaining of the target cells, no significant antiproliferative activity of our immunoconjugates against the cell lines tested was observed. One possible explanation for the lack of antitumor activity could be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells. This may have prevented an efficient immunotargeting of the cancer cells by the formation of soluble immune complexes.
Antibodies, Monoclonal↗