Search PubMed⌕ Search

Biomedical subjects

A Reichert

Publications and source records attributed to A Reichert.

At least 55 records · Page 3Linked to original sources
PubMed1988

Influence of 1-beta-D-arabinofuranosylcytosine conjugates of lipids on the growth and metastasis of Lewis lung carcinoma.

Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ara-C) were tested for their therapeutic activity on the growth and metastasis of Lewis lung carcinoma (3-LL). Among 1 ester-linked lipid conjugate (Ara-CDP-L-dipalmitin), 3 1-O-alkyl-lipid conjugates (ara-CDP-D,L-PBA, ara-CDP-D,L-PCA, ara-CDP-D,L-MBA) and a thioether-lipid conjugate (ara-CDP-D,L-PTBA) ara-CDP-D,L-PTBA, ara-CDP-D,L-PBA, and ara-CDP-L-dipalmitin produced the strongest tumor growth inhibition and increase of surviving animals in C57Bl6-mice bearing i.p.-implanted 3-LL. Furthermore these conjugates were superior to the parent compounds alone, or equimolar mixtures of the alkyllysophospholipid derivatives ET-18-OCH3 and ara-C. Successful therapeutic regimen consisted of 80-100 mg conjugate/kg, given i.p. daily for five consecutive days. Similar regimen injected shortly after the surgical removal of the primary tumor as adjuvant chemotherapy inhibited the metastasis of 3-LL to the lungs of the animals as demonstrated by an increase of survival time and the number of surviving animals.

Animals↗
PubMed1988

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks.

Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activity in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m2 and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m2. At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m2 consisted of ocular symptoms ('light flashes') accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m2/1 hour was considered the MTD. There were four deaths on study, all considered disease-related. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center. The recommended dose for phase II trials derived from our results is 12,550 mg/m2/2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Cytotoxic effects of ether lipids and derivatives in human nonneoplastic bone marrow cells and leukemic cells in vitro.

The effects of 2-lysophosphatidylcholine (2-LPC), the alkyl lysophospholipid derivatives (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-O-hexadecyl-sn-glycero-3-phospho-trimethyl-ammonio-hexanol, the 2-acetamide analog of platelet-activating factor (PAF) 1-O-octadecyl-2-acetamide-sn-glycero-3-phosphocholine, the thioether lysophospholipid derivative (TLP) BM 41.440 and the ether-linked lipoidal amine CP-46,665 on tritiated thymidine uptake and trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human leukemias. In both assay systems, a dose range of 1-20 micrograms/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells. The trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness: ET-18-OCH3 greater than BM41.440 greater than 2-acetamide analog of PAF. CP-46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 microgram/ml. The trimethyl-ammonio-hexanol compound showed only minor activity in the majority of tests, when added at concentrations less than 20 micrograms/ml. 2-LPC was rather ineffective. The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET-18-OCH3 and, sometimes, within the dose time frame tested of BM 41.440. All compounds tested except 2-LPC and the trimethyl-ammonio-hexanol compound were active also in this assay (inhibition of uptake greater than 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1987

Structure-cytotoxicity studies on alkyl lysophospholipids and some analogs in leukemic blasts of human origin in vitro.

Eleven lipids have been tested for cytotoxic (trypan blue dye exclusion) activity in cells from eight freshly explanted human leukemias in vitro. 4-Aminomethyl-1-[2,3-(di-N-decyloxy)N-propyl]-4-phenylpiperidine (CP-46,665), 1-mercapto-hexadecyl-2-methoxymethyl-rac-glycero-3-phosphocholine (BM 41.440), the 2-acetamide analog of platelet-activating factor (PAF) and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) were found among the most active compounds. 2-Lysophosphatidylcholine (2-LPC) showed the lowest activity. However, in addition there was variation among the results regarding the activity of the 1-octadecyl-rac-glycero-3-phosphocholine (ET-18-OH) and its D- and L-forms, but a significantly higher cytotoxic activity of D-ET-18-OH compared with L-ET-18-OH on the basis of 2-LPC as control after an incubation time of 48 hr. We conclude that with the limited number of structures available, this type of study is not sufficient to yield further information about the mode of the accumulation and toxicity of this type of lipids.

Antineoplastic Agents↗
PubMed1987

Antineoplastic activity of the thioether lysophospholipid derivative BM 41.440 in vitro.

Thioether lysophospholipid derivatives (TLP) inhibited the in vitro uptake of [3H]thymidine into blasts of eight leukemias and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Cytostatic and cytotoxic effects of TLP were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with greater than 5 micrograms/ml after an incubation of greater than 48 hr, but 10 to 20 micrograms/ml were necessary in solid tumors. Ester-linked 2-lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety in sn-1 and a stable sn-2 substitution of the molecule for the antineoplastic effect. To assess putative antileukemic selectivity, the cytotoxicity (trypan blue dye exclusion) of TLP was compared in human cell samples of 19 non-neoplastic bone marrows and 9 leukemias. Results revealed a significantly higher activity of the TLP BM 41.440 in leukemic blasts.

Antineoplastic Agents↗
PubMed1987

Prognostic implications of circulating immune complexes and Pseudomonas aeruginosa-specific antibodies in cystic fibrosis.

We re-examined the role of circulating immune complexes (CIC) in cystic fibrosis, by their serial measurement in 16 patients who had advanced lung disease and persistent specific antibodies to Pseudomonas aeruginosa in their serum. CIC were detected by 125I C1q-BA (IgG + IgM-IC) and Raji RIA (IgG-IC), and IgA-IC by a modification of the Raji RIA method. Serum precipitins to Ps. aeruginosa were detected by crossed-immunoelectrophoresis (XIE) and antibodies to alkaline protease (AP), elastase (EL) and exotoxin-A (EA) of Ps. aeruginosa were detected by ELISA technique. CIC were positive in greater than 50% of the samples in 8 patients (group A) and in less than 25% in the other 8 (group B); follow-up averaged 22 mo in group A and 26 mo in group B. The numbers of precipitins to Pseudomonas were equally high, and levels of antibodies to AP, EL, and EA of Ps. aeruginosa were similarly positive, in the 2 groups. In group A the CIC were mostly IgG-IC by Raji RIA (76%) and IgA-IC, whereas in group B C1q-binding IC (79%) and IgA-IC were more prevalent than IgG-IC by Raji RIA. Four group A children died during follow-up, together with one group B child in whom the CIC level had suddenly risen precipitously. We postulate that a high level of CIC in association with persistent specific-antibody response to Ps. aeruginosa heralds a poor prognosis in cystic fibrosis.

Adolescent↗
PubMed1987

Antineoplastic activity of conjugates of lipids and 1-beta-D-arabinofuranosylcytosine.

Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ARA-C) were tested in comparison with ARA-C, the ether lipid ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and their equimolar mixtures. The compounds were tested in vitro for cytotoxicity in the trypan blue dye exclusion test with cells from six different leukemias, one glioblastoma and two bronchogenic carcinomas of human origin. The compounds were given in vivo to assess their therapeutic activity against 3-Lewis lung carcinoma (3-LL) of syngeneic C57Bl6 mice. Although some of the conjugates have shown cytotoxic activity in vitro against the cell samples tested, they have not revealed higher cytotoxicity than ET-18-OCH3, ARA-C or their equimolar mixtures. In these experiments, ARA-CDP-D,L-MBA was the conjugates significantly inhibited tumor growth and also increased survival of C57Bl6 mice with intraperitoneally (ip) implanted 3-LL. In these experiments, ARA-CDP-D,L-PTBA, ARA-CDP-D,L-PBA, ARA-CDP-L-dipalmitin and ARA-CDP-D,L-PCA were more active than either the parent compounds ARA-C and ET-18-OCH3 alone or their equimolar mixtures. Furthermore, when the conjugates were injected as adjuvant chemotherapy shortly after the surgical removal of the primary 3-LL, they inhibited the metastasis of 3-LL to the lungs of the animals, demonstrated by an increase of the survival time and the number of surviving animals. The mode of action of these new antineoplastic compounds still is speculative.

Animals↗
PubMed1986

Ether lipid derivatives: antineoplastic activity in vitro and the structure-activity relationship.

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH3 and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppressed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 micrograms/ml). ET-18-OCH3 did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH3 seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 micrograms/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1-10 micrograms/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity. In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [3H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1985

Cytotoxicity of the alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) in cells from human tumors and leukemias.

The alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) inhibited the in vitro incorporation of tritiated thymidine into blasts of eight leukemias and cells of nine different solid tumors of human origin. This activity was well correlated with trypan blue dye exclusion, which was tested to assess cell membrane damage. Scanning electron microscopy revealed loss of cell surface features and severe cell membrane destruction after incubation with CP-46,665. These effects on thymidine uptake and single cell viability were accompanied by a clear loss of the reproductive capacities of human tumor and leukemic cells as measured in a human tumor stem cell assay after incubation with CP-46,665. The above-mentioned cytostatic and cytotoxic effects of CP-46,665 were dependent on dosage and incubation time. Destruction of leukemic blasts was often completed with greater than or equal to 5 micrograms/ml after an incubation of greater than or equal to 48 hr or greater than or equal to 10 micrograms/ml after an incubation of greater than or equal to 24 hr. Cells from solid tumors usually required a slightly higher drug concentration and longer incubation period for maximum killing. The alkyl-linked lipoidal amine CP-46,665 often showed considerably greater efficacy than did the alkyl-linked phospholipid rac-1-O-octadecyl-2-O-methylglycero-3-phosphocholine tested in comparison. In contrast to both drugs, 2-lysophosphatidylcholine showed only minor activity within the same dose range.

Adjuvants, Immunologic↗
PubMed1984

The sealing of vascular prostheses using autologous electrically activated blood.

Due to preclotting of the vascular prosthesis, autologous blood has shown good results provided that heparinization has not become necessary, or blood coagulation disorders are not present. In cases where replacement of the aorta is performed in the thoracic cavity with extracorporeal circulation or in the case of severe coagulopathies, preclotting with autologous blood does not show satisfactory results. In this presentation we report on a new method of sealing vascular prostheses with the help of autologous blood activated electrically "in vitro". The direct current changes the blood in vitro into a thrombogenic substance. Sealing is effected by placing the outer wall of the prosthesis in electrically activated blood.

Adult↗
PubMed1984

Cytotoxic effects of alkyl-lysophospholipids in human brain tumor cells.

The cytostatic activity of alkyl-lysophospholipids (ALP) was investigated in vitro with cells from 2 astrocytomas, 2 glioblastomas and a meningioma. In all lines the incorporation of [3H]thymidine into the tumor cells was inhibited by ALP. This effect was dependent on the ALP dose and incubation time. Incorporation rates were less than 5-10% of the control rates after an incubation time of more than 48 h with the ALP compound at a concentration of 20 micrograms/ml. 2-lysophosphatidylcholine, the ester-linked lysophospholipid, did not reveal any cytostatic effects. As a morphological criterion for severe cell damage, the trypan blue dye exclusion test was performed. Results were closely correlated with those of the thymidine incorporation inhibition assay. Further morphological evidence for actual damage of the tumor cell, caused by ALP incubation, was obtained by light microscopy of cytocentrifuge preparations and scanning electron microscopy. Membrane defects of tumor cells incubated with ALP were observed both in light and scanning electron microscopy, whereas untreated control cells remained intact. In cytocentrifuge smears of tumor cells, karyorrhexis occurred after 24 h of ALP treatment. After 48 h the cells looked almost completely damaged, and only fragments remained. Microvilli, blebs and ruffles, which indicate high surface activity and are characteristic morphological features of neoplastic astroglial cells in scanning electron microscopy, were severely disturbed by ALP incubation. Finally, the ability of tumor cells to adhere to glass and plastic surfaces was affected.

Antineoplastic Agents↗
PubMed1984

Nutrient intake of patients with cystic fibrosis.

Nutrient intake, anthropometric measurements, and pulmonary function were assessed in 26 young adult patients with cystic fibrosis (CF). Mean nutrient intakes, excluding those from vitamins and nutrient supplements, were less than the Recommended Dietary Allowances for folate for men and women and for iron and vitamin B-6 for women. Male cystic fibrosis patients consumed significantly more of 11 of 16 nutrients in comparison with men with Crohn's disease and men with functional gastrointestinal complaints. Female cystic fibrosis patients consumed significantly more of 9 of 16 nutrients than did women with gastrointestinal complaints. The relative body weight was less than 85% of standard in 65% of men and 50% of women with CF. Relative body weight was correlated with variables indicative of airflow obstruction, reduced vital capacity, and hyperinflation of lung volumes.

Adolescent↗
PubMed1983

Cytotoxicity of thioether-lysophospholipids in leukemias and tumors of human origin.

Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning electron microscopy revealed severe membrane destruction after incubation with thioether-lysophospholipids. Cytostatic and cytotoxic effects of thioether-lysophospholipids were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with greater than or equal to 5 micrograms/ml after an incubation of greater than or equal to 48 hr, but 10 to 20 micrograms/ml were necessary in solid tumors. Ester-linked 2-lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety in SN1 of the molecule for the antineoplastic properties of lysophospholipid analogues.

Adenocarcinoma↗
PubMed1983

Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells.

Alkyl-lysophospholipids (ALP) and related derivatives inhibited the in vitro incorporation of [3H]thymidine into seven different permanent cell lines derived from rat brain tumors. The cytostatic effect of ALP was dependent on dosage and incubation time. Naturally occurring 2-lysophosphatidylcholine did not exhibit cytostatic effects; under these conditions, the incorporation rates of [3H]thymidine were generally more than 100% of the controls. The trypan blue dye exclusion test, which was used to assess severe cell damage, correlated with the extent that [3H]thymidine incorporation was inhibited by ALP. Preincubation of ALP (rac-1-octadecyl-lyso-glycero-3-phosphocholine) for more than 8 min with a tetrahydropteridine-dependent O-alkyl cleavage enzyme preparation from rat liver microsomes destroyed almost all of the cytotoxic properties of ALP when tested at a concentration that previously inhibited tumor growth by more than 50%. [3H]Thymidine incorporation rates were greater than 100% for astrocytoma cells incubated with ALP after exposure to the alkyl cleavage enzyme. Comparison of the microsomal activities of the tetrahydropteridine-dependent alkyl-cleavage enzyme present in astrocytoma 78-FR-G-299 cells and the pleomorphic glioma 78-FR-G-219/S4 cells to that found in normal skin fibroblasts and rat livers revealed a markedly reduced activity in the neoplastic cell lines. Moreover, those tumor cells that were more resistant to ALP cytotoxicity (pleomorphic glioma, 78-FR-G-219/S4) had a 3-fold higher tetrahydropteridine-dependent cleavage activity than a more cytotoxic sensitive line (astrocytoma cells, 78-FR-G-299). Our results indicate that the low-alkyl-cleavage enzyme activities in these neoplastic cells in comparison to normal cells might be a factor in explaining the relatively high cytotoxicity of ALP in tumor cells.

Animals↗
PubMed1982

Alloantigen-induced suppressor- and memory cells in chronic lymphocytic leukemia.

T cell function was evaluated in patients with B cell type of chronic lymphocytic leukemia (CLL). Unseparated peripheral blood lymphocytes (PBL) and T cells from CLL patients stimulated in a primary allogeneic MLR were able to inhibit significantly a second MLR between the original responder (CLL) and stimulator (normal PBL) cell donors. Furthermore, it is shown the T lymphocytes from patients with CLL develop immunologic memory during the course of a primary MLR as evidenced by an enhanced response in secondary MLR. These results are discussed with respect to recently described imbalances of T cell subpopulations in CLL.

B-Lymphocytes↗
PubMed1982

Purification of human monocytes by adherence to polymeric fluorocarbon. Characterization of the monocyte-enriched cell fraction.

Human mononuclear cells were obtained from peripheral blood by density gradients. Monocytes can be purified after cultivation of 2 hours by a modified adherence procedure on membranes of gas-permeable polymeric fluorocarbon (teflon). After further cultivation of 24-48 hours, monocyte-enriched cell fraction can be easily detached from the membranes with a viability greater than 98% and a final cell yield of approximately 50% of the peripheral monocyte count. The cells showed the morphological and cytochemical characteristics of human monocytes and differentiated into dense monolayers of macrophages within 10 days of cultivation. Immune-autoradiography with iodine-125-labelled xenogeneic antimonocytic antisera and staining with several monoclonal antisera in an indirect immunofluorescence technique revealed up to 92% of these cells to carry monocytic characteristics. To show their functional integrity, monocytes obtained by this procedure were activated by 48 hours' cultivation with synthetic alkyl-lysophospholipids to inhibit the proliferation of autologous tumor cells.

Autoradiography↗