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E Hummel

Publications and source records attributed to E Hummel.

13 recordsLinked to original sources

Stability and cellular studies of [rac-1,2-bis(4-fluorophenyl)-ethylenediamine][cyclobutane-1,1- dicarboxylato]platinum(II), a novel, highly active carboplatin derivative.

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)ethylenediamine][cyclobutane-1, 1-dicarboxylato]platinum(II) complexes, rac- and meso-4F-Pt(CBDC), the evaluation of their structures, their tumor-inhibiting properties and their stability in physiological environment are described (reference complexes: the dichloro- and sulfatoplatinum(II) analogues, carboplatin and cisplatin). The most interesting diastereomer, rac-4F-Pt(CBDC), equals cisplatin and surpasses carboplatin in its effect on human breast cancer cell lines (MCF-7 and MDA-MB-231). Rac-4F-Pt(CBDC) is largely insensitive against attack of nucleophiles e.g. Cl-, a prerequisite for sufficient stability in vivo and for fewer side effects. In accordance with this, in vitro studies on the binding of rac-4F-Pt(CBDC) to albumin, the main plasma protein, show that the free, non-protein-bound fraction is relatively high, coming close to that of carboplatin. These properties are of importance for the transferability of the promising effects found in the cell culture experiments to in vivo conditions. The distinctly better anti-breast cancer activity of rac-4F-Pt(CBDC) than of carboplatin has been attributed to its ability to accumulate in the tumor cells. The human ovarian cancer cell line NIH-OVCAR-3 is also strongly inhibited by rac-4F-Pt(CBDC).

Breast Neoplasms↗

Synthesis of (S)-3,4-diaminobutanenitriles as precursors for 3-amino-GABA derivatives.

Starting from natural asparagine (1) a synthesis of the protected (S)-3,4-diaminobutanenitriles 5 and 8a-c via the beta-homoserine derivative 2 is described. The amino function in position 4 was introduced by Mitsunobu-coupling or by reductive amination when a strange deformylation of the amino aldehyde 7 was observed as a side reaction. The Mitsunobu-product 5 was converted into the dibenzylamine substituted GABA 6b which was investigated for its affinity at the GABA-A receptor.

Animals↗

Rises in anti-double stranded DNA antibody levels prior to exacerbations of systemic lupus erythematosus are not merely due to polyclonal B cell activation.

We investigated whether rises in anti-double stranded DNA (anti-ds DNA) antibody levels prior to disease exacerbations of systemic lupus erythematosus (SLE) are part of a restricted immune response or merely the consequence of polyclonal B cell activation. As possible inducers of polyclonal B cell activation, we analyzed, in addition, the role of clinically apparent infections in relation to changes in levels of anti-ds DNA and disease exacerbations. We prospectively followed 72 lupus patients who were examined for disease activity and infections at least every 3 months by history and physical examination according to a protocol. Once a month, we measured levels of IgG-class antibodies to an unrelated recall antigen (tetanus toxoid), levels of IgG-class antibodies to a viral antigen (cytomegalovirus late antigens [CMV-LA]), levels of total immunoglobulins G and M, and levels of anti-ds DNA (by ELISA and Farr assay). Thirty-three exacerbations and 31 infections were observed during a follow-up period of an average of 18.5 patient months. Twenty-four out of the 27 exacerbations accompanied by a positive test for anti-ds DNA were preceded by a significant rise in anti-ds DNA: in 17 cases by ELISA and in 22 cases by Farr assay. These 24 rises in levels of anti-ds DNA prior to the exacerbation were paralleled by a significant rise in levels of IgG-class anti-tetanus antibodies in 8 cases, anti-CMV-LA antibodies in 9 cases, total IgG in 7 cases, and total IgM in 15 cases. Median rise in anti-ds DNA, as measured both by ELISA and Farr assay, exceeded the median rise in anti-tetanus antibodies, anti-CMV-LA antibodies, and total IgG and IgM (P less than 0.0001). Only one infection was recorded within a period of 3 months prior to an exacerbation, whereas infections never occurred within a period of 3 months prior to a rise in anti-ds DNA. We conclude that rises in anti-ds DNA prior to exacerbations of SLE are largely due to preferential activation of anti-ds DNA-specific B cells and not merely to polyclonal B cell hyperactivity. Clinically significant infections are not related to rises in levels of anti-ds DNA nor to the induction of exacerbations in SLE.

Adolescent↗

[Monitoring infection at the intensive care unit--a multicenter pilot study].

During a period of 3 months an infection survey was carried out in 4 intensive care units (ICUs), 2 in Vienna, Austria, and one each in Ulm and Münster, Federal Republic of Germany, using a common protocol. A total of 329 patients was monitored prospectively. This pilot study was performed to evaluate the usefulness of parameters included in the monitoring form. It was attempted to characterize the patient populations of the four units. Mean duration of stay (1-12 days), mortality (8-26%), leading diagnosis upon admission, intubation rate (41-91%) and use of pulmonary artery catheter (12-35%) were distinctly different. The rate of patients admitted already with an infection was 9-43%, septicemia was diagnosed in up to 27% of the diseased. The rate of infection acquired in the unit was between 12 and 37%, the most frequent types were bronchopneumonia, septicemia and urinary tract infection. When septicemia patients were compared to non-septicemia patients who had been admitted for more than 3 days, it appeared that the latter stayed significantly shorter at the ICU and showed less frequently bronchopneumonia or urinary tract infection at the time of admission. Septicemia patients acquired more frequently additional infections like broncho-pneumonia or urinary tract infection while staying at the ICU. The median day of onset of septicemia was the fifth day and only in a quarter of cases diagnosis could be supported by a positive blood culture. The use of antibiotics in the 4 ICUs is compared and shows marked differences. Based upon experience with this type of infection survey a new modified protocol is introduced, which displays the time course of documented events.

Anti-Bacterial Agents↗

Sequential development of antibodies to specific Sm polypeptides in a patient with systemic lupus erythematosus: evidence for independent regulation of anti-double-stranded DNA and anti-Sm antibody production.

We describe a patient with systemic lupus erythematosus who, after a disease flare, sequentially produced antibodies to specific Sm polypeptides (demonstrated by counterimmunoelectrophoresis, immunoblotting, and RNA immunoprecipitation) concomitantly with the disappearance of anti-double-stranded DNA antibodies. Immunoblotting studies revealed that antibodies to the D polypeptide appeared first, followed by antibodies to BB' and E polypeptides, respectively. Our findings suggest that antibodies to the Sm-specific polypeptides do not occur simultaneously and that the regulation of their production is independent of that of antibodies to double-stranded DNA.

Adult↗

Radiology review.

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