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Biomedical subjects

R Manger

Publications and source records attributed to R Manger.

18 recordsLinked to original sources
PubMed1999

Heavy metals, lipid peroxidation, and ciguatera toxicity in the liver of the Caribbean barracuda (Sphyraena barracuda).

Human consumption of over 400 species of tropical fish containing polyether toxins (e.g. ciguatoxins, maitotoxins) causes ciguatera fish poisoning. The Caribbean barracuda (Sphyraena barracuda) is one of the most potent ciguatoxic fish. The objective of this study was to determine whether toxicity of 14 barracuda livers was correlated with lipid peroxidation. A significant correlation (p = 0.015, Pearson's correlation) between lipid peroxidation and toxicity of barracuda liver was found. Because iron and copper are well-known catalysts of hydroxyl radical production and lipid peroxidation in biological systems, the correlation between the concentrations of these metals in barracuda liver and lipid peroxidation and toxicity was also investigated. Cadmium was significantly correlated (p = 0.014) with the toxicity of barracuda livers. This study provides the first data concerning the concentration of iron, copper, and cadmium in the liver of the Caribbean barracuda. Of the three metals studied in barracuda liver, iron was the most abundant, followed by copper and cadmium. Lipid peroxidation was highly variable and detected in five (36%) of the liver samples. Lipid peroxidation was not statistically significantly correlated (p > 0.05) with concentrations of iron, copper, and cadmium in barracuda liver. Collectively, these findings provide additional evidence that lipid peroxidation can be a mechanistic component of ciguatera toxicity in the Caribbean barracuda.

Animals↗
PubMed1996

Collaborative evaluation of a method for the detection of Norwalk virus in shellfish tissues by PCR.

A multicenter, collaborative trial was performed to evaluate the reliability and reproducibility of a previously described method for the detection of Norwalk virus in shellfish tissues with the PCR (R.L. Atmar, F. H. Neill, J. L. Romalde, F. Le Guyader, C. M. Woodley, T. G. Metcalf, and M. K. Estes, Appl. Environ. Microbiol. 61:3014-3018, 1995). Virus was added to the stomachs and hepatopancreatic tissues of oysters or hard-shell clams in the control laboratory, the samples were shipped to the participating laboratories, and viral nucleic acids were extracted and then detected by reverse transcription-PCR. The sensitivity and specificity of the assay were 85 and 91%, respectively, when results were determined by visual inspection of ethidium bromide-stained agarose gels; the test sensitivity and specificity improved to 87 and 100%, respectively, after confirmation by hybridization with a digoxigenin-labeled, virus-specific probe. We have demonstrated that this method can be implemented successfully by several laboratories to detect Norwalk virus in shellfish tissues.

Animals↗
PubMed1993

Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide.

Two peptide analogs of the 37-62 sequence region of the HIV TAT protein bind tightly to the surface of A431 breast carcinoma cells. After conjugation to either of two poorly internalized anti-tumor antibody Fab fragments, the analogs enhanced the in vitro cell surface retention and internalization of the Fab fragments to the level of the whole antibodies. This was at the expense of some binding specificity in the case of 1.6 peptides/NRLU-10 Fab, but not in the case of 1.1 peptides/Fab. Enhanced retention may occur by enhanced bivalent binding of the Fab fragments. The internalized fraction of free peptide, but not of the Fab conjugates, is enhanced by chloroquine. The conjugates which were less specific for tumor cell binding may be useful for enhanced retention/internalization of specifically acting agents, for use at specific sites of injection, or against pre-separated target cell populations, while the more specific conjugate may be of interest for further development.

Amino Acid Sequence↗
PubMed1991

Immunoconjugates of Pseudomonas exotoxin A: evaluation in mice, monkeys, and man.

Immunotoxins of PE were constructed with stable thioether linkages using two monoclonal antibodies to ovarian cancer, OVB-3 and NR-LU-10. Antigens recognized by both antibodies have limited normal tissue distribution and are expressed on virtually all ovarian cancers. Both antibodies form highly potent conjugates (ID50 = 100 pg/ml) with high selectivity (greater than or equal to 4 logs) and can eliminate greater than or equal to 5 logs of tumor cells in vitro. The conjugates have been evaluated for efficacy in both ovarian and colon carcinoma ascites xenografts. In the ovarian model, the conjugates produce an increase in life span (ILS) of 200 to 300 with some cures against established but low tumor burden ascites. Increasing the tumor burden decreases efficacy and duration of responses. A lower ILS of 150 to 200 is achieved in the more aggressive colon model. However, the combination of immunotoxin with chemotherapy, which is ineffective on its own, demonstrated enhanced activity (ILS = 300). Toxicity of the conjugates is hepatic and easily monitored by liver function tests (LDH). Antitoxin responses are highly variable, but typically have a rapid onset and appear to be predicted by preexisting levels. Pilot clinical evaluation in ovarian cancer (intraperitoneal) is ongoing.

ADP Ribose Transferases↗
PubMed1990

Selective elimination of breast cancer cells from human bone marrow using an antibody-Pseudomonas exotoxin A conjugate.

A pancarcinoma monoclonal antibody (NR-LU-10), homogeneously reactive with human breast cancer cells, was conjugated to Pseudomonas exotoxin A. The immunotoxin was evaluated for its potential for purging breast cancer cells from human bone marrow. The immunotoxin NR-LU-10 antibody did not react with normal bone marrow preparations yet readily detected 1% contamination of bone marrow by MCF-7 breast cancer cells added to normal bone marrow without significantly inhibiting the colony-forming ability of bone marrow progenitor cells. NR-LU-10-Pseudomonas exotoxin A has potential for purging bone marrow of breast cancer cells without impairing the growth of bone marrow progenitor cells.

ADP Ribose Transferases↗
PubMed1989

Enhanced therapeutic efficacy of an immunotoxin in combination with chemotherapy against an intraperitoneal human tumor xenograft in athymic mice.

A mouse IgG2b anti-pan carcinoma monoclonal antibody, NR-LU-10, was shown to bind homogeneously to ascites xenografts of both ovarian and colon carcinoma. Following linkage to a highly potent holotoxin, Pseudomonas exotoxin A (PE), NR-LU-10 demonstrated high potency and selectivity in vitro (ID50 = 100 pg/ml; elimination of greater than or equal to 4.5 logs of cells). The conjugate was evaluated for therapeutic efficacy against a human colon tumor (HT-29) transplantable in the peritoneal cavity of nude mice. Beginning 3 days after HT-29 injection, mice received either three or six i.p. injections of 0.5 micrograms of unconjugated NR-LU-10 or immunotoxin conjugate (NR-LU-10/PE) every other day. Mice that received three or six treatments of NR-LU-10 alone had median survival times (MSTs) of 39 and 40 days, respectively, which did not differ significantly from the MST observed for the untreated control groups (MST = 35 days). In contrast, treatment with three or six injections of 0.5 micrograms NR-LU-10/PE exhibited significantly increased MSTs (P = 0.002) of 50 and 60 days, respectively. Coinjection of unconjugated NR-LU-10 (20 micrograms) and 0.5 micrograms of NR-LU-10/PE blocked the therapeutic effect of the immunotoxin (MST = 33 days). The therapeutic efficacy of NR-LU-10/PE was further enhanced against HT-29 when administered i.p. during and after cytoreductive chemotherapy. The i.p. administration of 300 mg/lg of cyclophosphamide plus 100 mg/kg of the chemoprotective drug, WR-2721, 10 and 17 days posttumor cell inoculation induced a significant increase in MST from 36 days to 59 days (P = 0.002). Interestingly, groups of mice that received either two, four, or seven treatments of NR-LU-10/PE following cytoreductive therapy exhibited a further significant increase (P = 0.001) in MSTs of 89, 97, and 105 days, respectively. Therefore, the use of immunotoxin therapy following cytoreductive chemotherapy significantly prolonged survival time of mice bearing the HT-29 colon tumor over that observed with chemotherapy or NR-LU-10/PE alone.

ADP Ribose Transferases↗
PubMed1987

Transformation by the oncogene v-fms: the effects of castanospermine on transformation-related parameters.

The effects of castanospermine on various parameters associated with transformation were examined in cells expressing the viral oncogene v-fms. Fischer rat embryo (FRE) cells transformed by the oncogene v-fms and grown in the presence of castanospermine reverted to a more normal cell morphology and accumulated fms protein within the endoplasmic reticulum. Treated cells attained contact inhibition of cell growth at a much lower cell density compared to the untreated controls. No effect of castanospermine on cell growth was observed for FRE cells transformed by a different oncogene v-fgr. Castanospermine-treated SM-FRE (v-fms transformed) cells reexpressed extracellular matrix fibronectin and exhibited an extensive actin-containing cytoskeleton similar to that of normal nontransformed FRE cells. Castanospermine treatment of SM-FRE cells resulted in a sixfold decrease in [3H]deoxyglucose uptake compared to that of the nonreverted SM-FRE cells. Again, no effect was observed in FRE cells transformed by the oncogene v-fgr (GR-FRE). These results further characterize the reversion caused by castanospermine and indicate that cell surface expression coordinately controls anchorage independent growth, cell morphology, contact inhibition of growth, and hexose uptake.

Actins↗
PubMed1986

Localization of the feline sarcoma virus fgr gene product (P70gag-actin-fgr): association with the plasma membrane and detergent-insoluble matrix.

The v-fgr oncogene codes for a unique transforming protein (P70gag-actin-fgr) that contains virus-specific determinants and cell-derived sequences for both a tyrosine-specific kinase domain and an actin domain. We examined the subcellular distribution of the v-fgr protein by immunofluorescence microscopy and various cell fractionation techniques. By immunofluorescence, the v-fgr protein was localized in a diffuse cytoplasmic pattern within transformed cells. The v-fgr protein was not detectable at substratum adhesion sites. Crude membrane preparations (P100) obtained from fgr-transformed cells contained elevated levels of P70gag-actin-fgr. Further analysis of membranes on discontinous sucrose gradients revealed that P70gag-actin-fgr cofractionated with plasma membranes. Using an alternate method of fractionation, we found that the majority of the v-fgr protein remained with the insoluble matrix obtained by treating cells with a buffer containing Triton X-100. When membranes were similarly treated with detergent, nearly all of v-fgr protein remained with the residual insoluble matrix. These results suggest that the transforming activity of P70gag-actin-fgr may be directed to subcellular cytoskeletal targets at or near the cytoplasmic face of the plasma membrane.

Actins↗
PubMed1985

Transformation by the v-fms oncogene product: role of glycosylational processing and cell surface expression.

The effect of glycosylational-processing inhibitors on the synthesis, cell surface expression, endocytosis, and transforming function of the v-fms oncogene protein (gp140fms) was examined in McDonough feline sarcoma virus-transformed Fischer rat embryo (SM-FRE) cells. Swainsonine (SW), a mannosidase II inhibitor, blocked complete processing, but an abnormal v-fms protein containing hybrid carbohydrate structures was expressed on the cell surface. SW-treated SM-FRE cells retained the transformed phenotype. In contrast, two glucosidase I inhibitors (castanospermine [CA] and N-methyl-1-deoxynojirimycin [MdN]) blocked carbohydrate remodeling at an early stage within the endoplasmic reticulum and prevented cell surface expression of v-fms proteins. CA-treated SM-FRE cells reverted to the normal phenotype. Neither SW, CA, nor MdN affected either endocytosis or the tyrosine kinase activity associated with the v-fms gene product in vitro. These results demonstrate the necessity of carbohydrate processing for cell surface expression of the v-fms gene product and illustrate the unique ability to modulate the transformed state of SM-FRE cells with the glycosylational-processing inhibitors CA and MdN.

1-Deoxynojirimycin↗
PubMed1985

[Problem discussion of allergic reactions in patients with infection-induced bronchial asthma in Candida colonization outside the respiratory tract].

Candida albicans colonization outside from the respiratory tract can occur as a side-effect of long lasting antibiotica therapy in patients with infection-induced asthma bronchiale and may induce in them allergic reactions. Based on own experiences the author reports on the frequency of Candida infections following antibiotica therapy and the effect of a therapy with Fungicidin on the number of dyspnoe attacks.

Anti-Bacterial Agents↗
PubMed1984

Cell surface expression of the McDonough strain of feline sarcoma virus fms gene product (gp 140fms).

The unique oncogene carried by the McDonough strain of feline sarcoma virus (SM-FeSV), called v-fms, directs the synthesis of a set of related glycoproteins, called gP 180gag-fms, gp 140fms, and gp 120fms. We have prepared antibodies to these proteins and used indirect immunofluorescence techniques on viable SM-FeSV transformed cells to demonstrate that fms-specific determinants are expressed on the external surface. The fms-specific fluorescence co-localized with clathrin and was detectable in clathrin-coated pits and endocytotic vesicles. Two cell surface labeling methods indicated that gp140fms was the only fms-related protein on the cell surface. In view of the relationship between the erbB oncogene product and the epidermal growth factor receptor, and the fact that growth factor receptors utilize clathrin-coated pits in endocytosis, we believe the gp140fms transforming protein of SM-FeSV also could function as an analog of a growth factor receptor.

Animals↗
PubMed1976

[Physician's decision making in evaluation of tuberculous patients assessed by a questionnaire (author's transl)].

By a questionnaire 88 chest physicians were asked anonymously for their opinion about 15 cases of tuberculosis with various problems (choice of chemotherapeutic regimens, duration of treatment, rehabilitation and other aspects) in regard to first or repeated treatment and in chronic tuberculosis. It can be demonstrated, that in the overwhelming number the evaluation of the cases is done with safety and that the recommendations of the advisory board for chest diseases and tuberculosis are noticed.

Antitubercular Agents↗
PubMed1975

[Causes of outpatient dropouts in the dispensary care of a chest clinic (author's transl)].

An investigation was made to point out, why 397 of total 2773 patients with 5524 consultations failed the fixed next consultation. 29 patients had died meanwhile. A special invitation was necessary in 368 (= 13%) of 2744 patients. The further behaviour of these patients after suitable advice and the importance of the diagnosis of their diseases in this connection were investigated. Failing of the patients can be diminished by systematical instructions.

Adult↗
PubMedDate not supplied

Enhanced in vitro tumor cell retention and internalization of antibody derivatized with synthetic peptides.

The Fab fragments of two antitumor monoclonal antibodies, NR-ML-05 and NR-LU-10, have been covalently derivatized with synthetic peptides designed to provide secondary sites of attachment to enhance their retention on tumor cells. Analogs of the peptide "GALA", an amphipathic peptide previously reported to interact with uncharged lipid bilayers, gave antibody conjugates of different molecular weight and bound peptide stoichiometry when attached to Fab fragments using the heterobifunctional cross-linker sulfo-SMCC. This attached peptide enhanced the retention and internalization of Fab fragments of NR-ML-05 on FEMX human melanoma cells, but not of NR-LU-10 on HT-29 human colon carcinoma cells, indicating that this effect might be specific for individual tumor antigen-antibody systems. This peptide appeared to increase nonspecific interactions of the conjugate with antigen-negative cells. Other membrane-active peptides were also tested. None were as effective as the "GALA" analogs. A synthetic ion channel peptide attached to NR-ML-05 Fab exhibited the greatest enhanced internalization of these tested peptides.

Amino Acid Sequence↗
PubMedDate not supplied

Developing a centre for health information and promotion.

Following the successful application for nursing development unit funding, the children's outpatient department within the Child Health Directorate of the University Hospital, Southampton, has developed a number of ambitious plans to promote nursing initiatives, one of which was the creation of a centre for health information and promotion. This article describes this development.

Caregivers↗