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C Peters

Publications and source records attributed to C Peters.

At least 163 records · Page 9Linked to original sources
PubMed1996

In vivo 125I-erythropoietin pharmacokinetics are unchanged after anesthesia, nephrectomy and hepatectomy in sheep.

Knowledge regarding the in vivo metabolic fate of the glycoprotein erythropoietin (EPO) is incomplete. To determine whether EPO pharmacokinetics are perturbed by ablation of the kidneys or liver or by anesthesia, EPO pharmacokinetic parameters were determined in adult sheep. Animals were studied in a paired manner, with and without deep barbiturate anesthesia and before and immediately after nephrectomy or hepatectomy accompanied by deep barbiturate anesthesia. Hepatectomy was accomplished with the liver left in situ, by occlusion of the arterial hepatic blood supply and diversion of portal venous flow to the jugular vein. After i.v. administration of tracer amounts of 125I-labeled recombinant human EPO, multiple blood samples were taken over 6 to 7 hr and analyzed for EPO immunoprecipitable radioactivity. EPO pharmacokinetic parameters were derived using a noncompartmental system analysis applied to the data on EPO immunoprecipitable radioactivity. No significant differences were detected for plasma clearance, distribution volume, mean residence time and alpha and beta half-lives examined under each of the three paired study conditions. Contrary to speculation by others, results of the present study make it highly unlikely that removal of the terminal sialic acid moieties of EPO contributes significantly to the metabolism of EPO. Because removal of the liver and kidney had no effect on EPO elimination, the metabolic degradation of EPO occurs in a tissue compartment that is yet to be defined. We speculate that the bone marrow is the most likely tissue with primary responsibility for the metabolism of EPO.

Anesthetics↗
PubMed1995

The first reported outbreak of diarrheal illness associated with Cyclospora in the United States.

OBJECTIVE: To investigate and characterize the epidemiology of a diarrheal outbreak associated with a potentially new pathogen, Cyclospora species (previously referred to as Cyanobacteria [blue-green algae]-like bodies). DESIGN: Three retrospective cohort studies supported by laboratory studies, environmental investigation, and community surveillance. SETTING: A hospital in Chicago. PARTICIPANTS: Housestaff physicians and hospital administrative staff. MEASUREMENTS: Identification of clinical features associated with illness and potential risks for acquisition of infection. RESULTS: Illness was characterized by watery diarrhea, abdominal cramping, decreased appetite, and low-grade fever. Symptoms typically occurred in a distinctive cycle of remissions and exacerbations lasting up to several weeks. Stool cultures and examinations for known ova and parasites were negative. Microscopic examination of stool specimens from 11 ill persons showed many spherical bodies, 8 to 10 microns in diameter, that were identified as Cyclospora organisms. The organisms disappeared by 9 weeks after onset of illness in the 7 patients from whom follow-up specimens were obtained. Epidemiologic studies implicated tap water from a physicians' dormitory as the most likely source of the outbreak. Environmental investigation suggested that stagnant water in a storage tank may have contaminated the water supply after a pump failure. CONCLUSIONS: This is the first reported outbreak of diarrhea associated with Cyclospora in the United States. Cyclospora may be a human enteric pathogen able to produce bouts of acute and relapsing diarrhea, and it should be considered in assessments of patients with unexplained, prolonged diarrheal illness.

Adult↗
PubMed1995

Two site-directed mutations abrogate enzyme activity but have different effects on the conformation and cellular content of the N-acetylgalactosamine 4-sulphatase protein.

The sulphatase family of enzymes have regions of sequence similarity, but relatively little is known about either the structure-function relationships of sulphatases, or the role of highly conserved amino acids. The sequence of amino acids CTPSR at position 91-95 of 4-sulphatase has been shown to be highly conserved in all of the sequenced sulphatase enzymes. The cysteine at amino acid 91 of 4-sulphatase was selected for mutation analysis due to its potential role in either the active site, substrate-binding site or part of a key structural domain of 4-sulphatase and due to the absence of naturally occurring mutations in this residue in mucopolysaccharidosis type VI (MPS VI) patients. Two mutations, C91S and C91T, altering amino acid 91 of 4-sulphatase were generated and expressed in Chinese hamster ovary cells. Biochemical analysis of protein from a C91S cell line demonstrated no detectable 4-sulphatase enzyme activity but a relatively normal level of 4-sulphatase polypeptide (180% of the wild-type control protein level). Epitope detection, using a panel of ten monoclonal antibodies, demonstrated that the C91S polypeptide had a similar immunoreactivity to wild-type 4-sulphatase, suggesting that the C91S substitution does not induce a major structural change in the protein. Reduced catalytic activity associated with normal levels of 4-sulphatase protein have not been observed in any of the MPS VI patients tested and all show evidence of structural modification of 4-sulphatase protein with the same panel of antibodies [Brooks, McCourt, Gibson, Ashton, Shutter and Hopwood (1991) Am. J. Hum. Genet. 48, 710-719]. The loss of enzyme activity without a detectable protein conformation change suggests that Cys-91 may be a critical residue in the catalytic process. In contrast, analysis of protein from a C91T cell line revealed low levels of catalytically inactive 4-sulphatase polypeptide (0.37% of the wild-type control protein level) which had missing or masked epitopes, suggesting an altered protein structure or conformation. Subcellular fractionation studies of the C91T cell line demonstrated a high proportion of 4-sulphatase polypeptide content in organelles characteristic of microsomes. The aberrant intracellular localization and the reduced cellular content of 4-sulphatase polypeptide was consistent with the observed structural modification leading to retention and degradation of the protein within an early vacuolar compartment.

Animals↗
PubMed1995

Kinetic evaluation of nonlinear drug elimination by a disposition decomposition analysis. Application to the analysis of the nonlinear elimination kinetics of erythropoietin in adult humans.

The disposition-decomposition analysis (DDA) methodology enables isolation of the overall elimination and distribution effects in pharmacokinetics and facilitates analysis which focuses on drug elimination kinetics and does not require a specific structured modeling of drug distribution processes. A computer algorithm enables a curve fitting and a kinetic estimation by integration of the convolution type integrodifferential equation in the DDA. The approach is demonstrated in an analysis of the nonlinear disposition kinetics of erythropoietin (Epo) in 10 healthy, adult human subjects who each received 10, 100, and 500 U/kg i.v. bolus doses of Epo. The nonlinearity is analyzed according to a Michaelis-Menten type nonlinear elimination function, considering simultaneous fitting to the data from all three doses in each subject. The simultaneous fittings produced estimates of the Michaelis-Menten parameters (mean, % cv) Vm (901 mU/mL/h, 19.4%) and km (4814 mU/mL, 24.6%). A linear clearance parameter is defined as the asymptotic clearance value approached when the drug level decreases toward zero. The degree of nonlinearity reached from various dosings was quantified in terms of a clearance ratio which is defined as the ratio between the linear clearance and the clearance estimated for the maximum drug concentration encountered at the given dose level. The subjects showed very little nonlinearity at the 10 U/kg dosing with a mean clearance ratio of 1.07 (2.1% CV) A statistically significant increase in the degree of nonlinearity was observed in the Epo elimination kinetics as the dosing level was increased to 100 and 500 U/kg, reaching clearance ratios of 1.66 (14% CV) and 4.33 (27% CV), respectively. A zero value for the global elimination rate parameter in all 30 dosings indicates that Epo's elimination is entirely accounted for by nonlinear pathway(s).

Adult↗
PubMed1995

Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.

Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.

Animals↗
PubMed1995

Ovine bone marrow extracellular matrix and soluble protein extraction: fetuin amino terminus microheterogeneity.

In this article, the authors describe a new method using phosphate-buffered saline for the initial extraction of extracellular matrix (ECM) and soluble proteins from hematologic tissues. Direct comparisons between this method and previously reported methods demonstrate superior total protein yields with the novel technique in a fraction of the time for these ovine hematologic tissues: bone marrow, marrow aspirate, spleen, liver, and blood. Analysis by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining demonstrate comparable protein patterns with this method and a previously reported method. This method also successfully extracts the ECM glycoproteins fibronectin and laminin as well as the proteoglycan, chondroitin sulfate from marrow. These findings are demonstrated by Western and dot blotting. Bone marrow ECM and soluble proteins extracted by the novel method stimulate myeloid progenitor growth in a methylcellulose assay. Using an assay for elastase inhibitory capacity, the authors demonstrate that alpha 1-proteinase inhibitor, the principal inhibitor of neutrophil elastase, is present and that its activity is preserved in bone marrow samples extracted with this team's method. In contrast, very low total protein yields are obtained with the method used previously to recover hemonectin, a rabbit bone marrow ECM granulocytic cytoadhesion molecule. This team's novel procedure, which extracts ECM and soluble proteins from small samples of tissue in a rapid, efficient, and reproducible manner, greatly enhances the analysis of these proteins from tissue culture, animal, and human clinical samples. In addition, with purification by chromatofocusing chromatography and molecular sieving gel electrophoresis, N-terminal amino acid sequencing could be performed on a developmentally regulated marrow protein with biochemical properties similar to those of hemonectin and the plasma protein fetuin. The authors propose that this novel technique be used for the initial extraction of ECM and soluble proteins from hematologic tissues and that subsequent, definitive recovery of insoluble proteins be accomplished using previously reported, though less efficient, methods.

Amino Acid Sequence↗
PubMed1995

Remote telemetry: new twists for old technology.

Availability of telemetry beds was increased cost-effectively by providing telemetry on medical/surgical units with remote monitoring at designated critical care areas. Guidelines were developed for patient selection, education, clinical policy and procedure. A two-hour inservice was completed by all medical/surgical nurses and after a pilot study the system was implemented on three medical/surgical units.

Cost-Benefit Analysis↗
PubMed1995

The role of macrophage receptors in adhesion and uptake of Leishmania mexicana amastigotes.

Amastigotes of the protozoan parasite Leishmania proliferate in phagolysosomes of mammalian macrophages. Propagation of the infection is considered to occur by host-cell rupture and uptake of released parasites by uninfected macrophages. In this study, the kinetics of binding of L mexicana mexicana amastigotes to COS cells and to COS cells transfected with three different macrophage receptors (FcRII-B2, receptor for the Fc-domain of immunoglobulins; CR3, complement type 3 receptor and the mannose receptor) is compared to the rate of adhesion to peritoneal macrophages. Amastigotes isolated from macrophages cultivated in vitro bind with slow, sigmoid kinetics to COS cells expressing either of the three receptors, or to peritoneal macrophages. In contrast, amastigotes isolated from mouse lesions bind with rapid, hyperbolic kinetics to COS cells expressing the Fc receptor or to peritoneal macrophages but with slow, sigmoid kinetics to COS cells expressing the CR3 or the mannose receptor. As shown by immunofluorescence experiments, lesion-derived amastigotes contain host-derived immunoglobulins (Ig) but no complement component 3 at their surface. It is concluded that amastigotes contain no intrinsic ligand at their surface, which enables high-affinity interactions with macrophages. Opsonization by specific Ig may be of relevance in vivo because firstly, in cryosections of mouse lesions extracellular amastigotes containing surface Ig can be detected and, secondly, B cell-deficient mice reconstituted with parasite-specific Ig show a modest increase in the rate of lesion development. In addition, it is shown that amastigotes are internalized by COS cells and grow in large parasitophorous vacuoles similar to those observed in macrophages.

Adhesiveness↗
PubMed1995

Haemostasis activation markers in plasma of patients with benign and malignant gynaecological tumours: a pilot study.

Coagulation and fibrinolysis activation have been investigated in fifty-eight women with recently detected gynaecological tumours. Twenty-six were benign and 32 malignant: of the last group nine patients had metastases. A control group consisted of 31 age-matched healthy women. Prothrombin fragment 1 + 2, thrombin-antithrombin III and D-dimer were measured. The median values of all analytes were significantly higher in the malignant tumour group, but not in the benign tumour group, as compared to the control group. The group of patients with a gynaecological tumour and metastases differed from the non-metastasized tumour group in prothrombin fragment 1 + 2, thrombin-antithrombin III and D-dimer. In the non-metastasized malignant tumour group solely prothrombin fragment 1 + 2 was significantly higher than in the benign tumour group. Coagulation and fibrinolysis predominating as can be derived from the elevated D-dimer/thrombin-antithrombin III and D-dimer/prothrombin fragment 1 + 2 ratios. The studied constituents do not enable a differentiation between the benign and malignant processes. However, as the differences of these values in both malignant tumour groups were significant, this might be used to trace the existence of metastases in gynaecological tumours. Investigation of these analytes in several specific types of gynaecological tumours might be clinically relevant.

Biomarkers, Tumor↗
PubMed1995

Immune thrombocytopenia and elemental mercury poisoning.

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

Adolescent↗
PubMed1995

Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. BFM Relapse Study Group.

The purpose of this study was to determine the therapeutic efficacy of different treatment strategies, namely chemotherapy, allogeneic and autologous bone marrow transplantation (BMT), for extramedullary relapse of acute lymphoblastic leukemia (ALL) in children in second or subsequent remission. Between 1983 and 1993, 165 patients up to 19 years of age with extramedullary relapse of ALL were registered in the multicenter ALL-REZ BFM trials. One hundred and thirty four children received chemotherapy only; 17 children were grafted from HLA-identical sibling donors 152 days (46-392 days) after diagnosis of relapse, and 14 children underwent autologous BMT after a median time of 137 (range 23-300) days. Event-free survival (EFS) at 5 years was 0.47 +/- 0.05 for patients receiving chemotherapy: 0.76 +/- 0.07 for late, 0.33 +/- 0.08 for early and 0.33 +/- 0.07 for very early relapsed patients. Sixty five patients are in complete remission (CR), 61 patients relapsed, 5 died from therapy related complications, 2 patients in CR were lost to follow-up and one patient developed a second malignancy. For patients who had undergone BMT, EFS at 5 years was 0.36 +/- 0.10 without significant difference between autologous BMT (8 of 14 in CR, 6 relapsed) and allogeneic BMT (6 of 17 in CR, 4 died of acute toxicity, and 7 relapsed).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Impact of megatherapy in children with high-risk Ewing's tumours in complete remission: a report from the EBMT Solid Tumour Registry.

The European BMT Solid Tumour Registry (EBMT-STR) received reports from 21 European transplant centers on 63 patients (50 Ewing's sarcomas and 13 peripheral neuroectodermal tumours) in first (n = 32) or second CR (n = 31) consolidated with megatherapy and BM and/or PSC rescue between December 1982 and November 1992. There were 31 males and 32 females with a median age of 12 years (range 1-30 years) at megatherapy. The median follow-up time since megatherapy is 4 years (range 1 month to 10 years), Thirty-two patients with metastatic disease at diagnosis (22 had metastases to the bone and/or bone marrow) and consolidated in CR1 reached an actuarial event-free survival (EFS) of 21% at 5 years. Thirty one patients in CR2 achieved an actuarial EFS of 32% at 5 years. Favourable outcome was limited to relapse patients with localised disease at initial diagnosis. Distant relapse had a more favourable prognosis than local failure. Analysis of the different megatherapy strategies could not identify a significantly superior approach, nor is there convincing evidence in favour of double graft procedures. From the above results it appears that consolidation treatment by megatherapy contributes to improved EFS rates in high-risk patients compared with historical experience. Major questions for the future to be addressed prior to randomised studies include agreement on the definition of high-risk patients and the most efficient megatherapy procedure.

Adolescent↗
PubMed1995

[Collection and long-term preservation of peripheral stem cells].

The methods of collection and storage of peripheral blood stem cells are described, and the harvesting after conditioning with cytokines and/or myelosuppressive therapy is discussed. It could be demonstrated that the combination of cytostatics and cytokines gives the best yield and enables to collect a sufficient amount of peripheral bloodstem cells for a successful engraftment after myeloablative therapy with only few aphereses.

Antineoplastic Agents↗
PubMed1995

Effect of retinoic acid on expression of transforming growth factor-beta by retinal pigment epithelial cells in culture.

OBJECTIVE: To study the effect of retinoic acid on the expression of transforming growth factor-beta (TGF-beta) by human retinal pigment epithelial (RPE) cells in culture. MAIN OUTCOME MEASURES: Expression of TGF-beta 1 by RPE cells after 24 hours in culture at the messenger RNA level (Northern analysis) and the protein level (enzyme-linked immunosorbent assay [ELISA]). RESULTS: On the basis of cell morphology, growth characteristics and the results of immunohistochemical studies, we concluded that the cells used in these experiments were RPE in origin. Immunohistochemical studies confirmed TGF-beta 1 expression by the RPE cells in culture. Densitometry showed that retinoic acid reduced the level of TGF-beta 1 mRNA expression by 41% compared with control samples. ELISA showed that retinoic acid inhibited TGF-beta expression when compared with the baseline level of TGF-beta in media from RPE cells in culture. CONCLUSIONS: These findings may have implications for the pharmacotherapy of proliferative vitreoretinopathy.

Blotting, Northern↗
PubMed1994

Biogenesis of lysosomal membranes.

Lysosomal membrane glycoproteins are highly glycosylated proteins decorating the luminal surface of lysosomal membranes. Their biosynthetic route from the rough endoplasmic reticulum to the lysosomal compartment has been elucidated during recent years. Signals for intracellular sorting have been identified and characterized. The function of these proteins remains to be determined. Besides resident proteins the lysosomal membrane harbours at least one transient passenger, lysosomal acid phosphatase, which is sorted as a membrane-bound precursor like resident lysosomal membrane proteins and liberated from the membrane by limited proteolysis upon arrival in dense lysosomes.

Amino Acid Sequence↗
PubMed1994

Growth-dependent regulation of cellular ceramides in human T-cells.

The role of ceramide, a putative lipid second messenger in the regulation of cell growth, was investigated in T-lymphocytes. An inverse relationship between the cellular concentrations of ceramide and the proliferative capacity of human T-lymphocytes was observed for cells treated with either interleukin-2 or phorbol ester plus ionomycin. The same relationship between cellular ceramide concentrations and DNA synthesis also was observed for cells derived from a cultured T-cell line, the Jurkat T-cells. Alternative approaches for modulating the cellular ceramide concentrations were employed to determine the relationship between sphingolipids and cell growth. Treatment of normal T-lymphocyte cultures with exogenous cell-permeable ceramide analogues or sphingosine stereoisomers decreased DNA synthesis. A similar effect was seen with stearylamine. Cells treated with D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of UDP-glucosyl:ceramide transferase, accumulated cellular ceramide concentrations and had decreased DNA synthesis. These results define a correlation between the concentration of cellular ceramides and the capacity of T-lymphocytes to proliferate. However, the addition of bacterial sphingomyelinase to the T-cell medium caused an increase in ceramide concentrations (presumably at the plasma membrane), which did not affect cell growth. These results support the hypothesis that functionally distinct pools of ceramide may reside within the T-cell.

Cell Division↗