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Biomedical subjects

J Roboz

Publications and source records attributed to J Roboz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Early diagnosis and monitoring of transplanted human malignant mesothelioma by serum hyaluronic acid.

Serum concentrations of unhydrolyzed hyaluronic acid (HA) in nude mice bearing human malignant mesothelioma xenografts were determined by size-exclusion chromatography. HA rose to 8-16 micrograms/mL (controls: less than 1 micrograms/mL) by the fourth to fifth day after tumor (epithelial) transplantation, 3 to 5 days before palpability. Decreases in HA during late tumor growth are probably attributed to tumor necrosis, based on the observation that HA was 2.5 times less in necrotic than in viable tumor tissues. This serum biomarker, recognizable before physical detectability of xenografted tumors, should have applicability to monitoring experimental chemotherapy in mice and to early diagnosis and monitoring of human malignant mesothelioma.

Animals↗
PubMed1988

Collisional activation decomposition of actinomycins using tandem mass spectrometry.

The collisional activation (xenon) decomposition of actinomycin V, dactinomycin, 7-nitrodactinomycin, 7-aminodactinomycin, and a mixture of dactinomycin, actinomycin C1 and actinomycin C2 was studied using a triple-quadrupole mass spectrometer with fast atom bombardment (xenon) ionization. Fragmentation pathways of the structurally significant ions were rationalized by assuming an initial McLafferty rearrangement at the ester linkage between the methylvaline and the threonine of both rings to form linear pentapeptides, followed by fragmentation in either pentapeptide yielding typical sequence ions and sequence cleavages from both rings.

Dactinomycin↗
PubMed1987

Role of individual serum pentitol concentrations in the diagnosis of disseminated visceral candidiasis.

A technique was developed for separating total serum pentitols into individual arabinitol, adonitol and xylitol and determining their relevance for the diagnosis of disseminated candidiasis. Pentitols were separated as trimethylsilyl derivatives on two 25 m long, bonded methyl silicone columns with a 0.32 mm i.d., and quantified by selected ion monitoring of their protonated molecular ions obtained in chemical ionization. The 173 samples studied were divided into culture-positive, culture-negative, and no-culture groups. Twelve percent of all samples were false positives by the total pentitols method due to increased adonitol and/or xylitol. The continued use of the total pentitols method is, nevertheless, recommended because of its convenience; however, samples with increased total pentitols (and normal creatinine) should be reanalyzed for individual pentitols. Increased arabinitol and normal creatinine are indicative of candidiasis even when blood cultures are negative.

Candidiasis↗
PubMed1985

Analytical and pharmacological studies on a new antineoplastic tripeptide, PTT.119.

The new synthetic tripeptide, p-fluoro-L-phenylalanyl-m-bis-(2-chloroethyl)-amino-L-phenylalanyl-methi onine ethylester hydrochloride, PTT.119, an alkylating agent, is currently undergoing preclinical trials as an antineoplastic agent. The molecular composition, C29H39N4O4SCl2F, was confirmed by desorption chemical ionization mass spectrometry with accurate mass measurement. A high-performance liquid chromatographic technique was developed for the quantification of PTT.119 in cell culture medium and serum. Incubation of 5 X 10(5) mammary tumor cells (MJY-alpha)/ml tissue culture medium with 25 micrograms PTT.119/ml for 60 min (37 degrees C) removed 68% of the tripeptide from the medium. This corresponds to an uptake of 51 fmol PTT.119/tumor cell. Cell death, assessed 5 days after treatment, was directly proportional to the time-dependent removal of PTT.119 from the cell culture medium.

Antineoplastic Agents↗
PubMed1985

Polybrominated biphenyls in model and environmentally contaminated human blood: protein binding and immunotoxicological studies.

A review and summary is given of analytical, biochemical, and immunological studies made following an immunodiagnostic investigation which revealed significant decreases in the numbers, and changes in the functional integrity, of both T-and B-lymphocytes in a group of Michigan dairy farmers exposed to polybrominated biphenyls (PBB) which had been inadvertently introduced into the food chain in 1973. A quantification technique based on selected ion monitoring of bromine anions, obtained in negative chemical ionization, permitted determination of 10-35 pg of individual PBB congener per mL serum, a 20-fold improvement over electron capture gas chromatography. An in vitro spiked system was established and shown to be a representative model of environmentally contaminated blood. Immunoprecipitation followed by mass spectrometric quantification determined that the distribution of PBB among plasma, erythrocytes, mononucleocytes and polymorphonucleocytes was 89:9:less than 1:less than 1. In plasma 80% of the PBB was bound to apolipoproteins B and A in a 3:1 ratio. No preferential absorption of PBB congeners was found in the blood compartments suggesting that changes in the relative abundances of PBB congeners observed in longitudinal studies on Michigan subjects reflect differences in excretion rates or metabolism. A repeat in 1981 of the immunodiagnostic tests conducted in 1976 revealed a virtually complete persistence of the immune dysfunctions in the Michigan farmers exposed to PBB a decade ago.

Agricultural Workers' Diseases↗
PubMed1985

Hyaluronic acid content of effusions as a diagnostic aid for malignant mesothelioma.

A high-performance liquid chromatographic technique, using a size exclusion column (TSK-5000PW), has been developed for the quantification of hyaluronic acid (HA) in pleural and peritoneal effusions. Sample preparation requires only a 100-fold dilution of the exudate with phosphate buffer prior to analysis. Chromatographic conditions are: 0.05 M phosphate buffer (pH, 5.0) mobile phase at a flow rate of 1.0 ml/min, ultraviolet absorbance detection at 200 nm. The method resolves HA from all other glycosaminoglycans. The presence of HA is confirmed by the removal of the HA peak (retention time, approx. 5.3 min) by incubation of a second sample aliquot with hyaluronidase. Effusions of 13 of 14 patients with confirmed malignant mesothelioma contained HA in the 0.3 to 11.1 mg/ml range. In only one case was no HA detected. None of the effusions from 56 control patients with various other primary tumors contained detectable HA, i.e., there were no false positives. An unidentified peak, not susceptible to hyaluronidase appeared in 11% (6 of 56) of the controls. A single mesothelioma case was correctly identified in a group of 10 coded samples. It is suggested that an effusion with an HA concentration greater than 0.25 mg/ml, confirmed by hyaluronidase susceptibility, is an indication of the presence of malignant mesothelioma. The test is simple and rapid, and it is recommended that any effusion of uncertain etiology be screened for the presence of HA.

Ascitic Fluid↗
PubMed1984

Incorporation of 15N from glycine into uric acid in gout: a follow-up study.

Over-incorporation of 15N-labeled glycine into uric acid indicates over-production of uric acid by de novo purine biosynthesis. This metabolic aberration, though considered to be inborn (3), may be modified by changing of life style, aging and long-term therapy. In the patient under study, the protracted use of allopurinol seems to have played the most important role. Aging contributed to a certain extent, and changing life style was the least significant factor.

Adult↗
PubMed1984

Determination of polyols in serum by selected ion monitoring.

We used gas chromatography-chemical ionization mass spectrometry with selected ion monitoring of the (M-59)+ ions to determine polyols (as their peracetyl derivatives) in serum. The internal standard was 2-deoxygalactitol. Mean (and SD) polyol concentrations (mg/L) in 33 normal sera were: erythritol 0.45 (0.14), threitol 0.20 (0.06), adonitol 0.06 (0.02), arabinitol 0.37 (0.12), xylitol 0.05 (0.02), mannitol 0.41 (0.45), galactitol 0.15 (0.11), sorbitol 0.16 (0.11). Arabinitol determined in the same 33 normal sera by trimethylsilylation was 0.39 (0.13) mg/L. In 32 samples from cancer patients with normal creatinine, all polyol concentrations were in the normal range except for seven increased erythritol and one increased threitol concentrations. In all six patients with renal dysfunction we found increased erythritol and arabinitol, and increased threitol and mannitol in four of the six. Initial results showed that only arabinitol concentrations increased in invasive candidiasis.

Candidiasis↗
PubMed1984

Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis.

Four patients with recurrent cystine stones and 5 with rheumatoid arthritis (RA) were studied. After a single dose of D-penicillamine to cystinuric patients, cystine excretion decreased considerably. Cysteine-penicillamine mixed disulfide (CSSP) and penicillamine disulfide (PSSP) metabolites appeared within 1-2 h (CSSP/PSSP approximately equal to 4.8-8.6). In RA, cystine excretion remained negligible (CSSP/PSSP approximately equal to 1.4-2.9). With daily D-penicillamine in RA (CSSP/PSSP ratios were usually greater than 7 in those with favorable clinical response. CSSP/PSSP ratios may help to predict prognosis and adjust penicillamine dosage. Coadministration of probenecid is contraindicated in hyperuricemic cystinuric patients because of increased cystine and decreased CSSP and PSSP excretion.

Arthritis, Rheumatoid↗
PubMed1983

Dialyzability of methyl-GAG.

Methyl-GAG at low doses was administered to an anephric male patient with metastatic hypernephroma, who required hemodialysis. No toxicity was observed. Measurement of serum levels of methyl-GAG showed that the drug is dialyzable. Thus, when methyl-GAG is considered for patients who are anephric and are being dialyzed, full doses are allowable. In addition, dialysis should be effective in rapidly eliminating the drug in patients who develop toxic effects.

Adenocarcinoma↗
PubMed1982

Quantitation of harringtonine and homoharringtonine in serum by high-performance liquid chromatography.

Harringtonine and homoharringtonine are naturally occurring alkaloids with demonstrated antineoplastic activity against certain types of leukemias in cell cultures, experimental animals, and initial clinical trials. Sample preparation consists of addition of the internal standard (one compound used as the internal standard for the other), solvent extraction with methylene chloride, washing with ammonium formate, and evaporation to dryness. The residue is dissolved in the mobile phase (40% methanol-60% 0.1 M ammonium formate) and an aliquot is chromatographed on a microC 18 reversed-phase column (flow-rate 1.5 ml/min). Peaks are detected with a spectrophotofluorimeter by monitoring the emission at 320 nm with excitation wavelength of 280 nm. Limit of detection is 10 ng/ml (20 nM) for both compounds; reproducible quantitation can be made to 30 ng/ml (60 nM).

Alkaloids↗
PubMed1982

Comparison of the interaction of antineoplastic aminoanthraquinone analogs with DNA using competitive fluorescence polarization.

1,4-dihydroxy-5-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione one (NSC 287836) and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione diacetate (NSC 287513) have shown activity against solid tumors and are now in Phase I clinical trials. Fluorescence polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA (Richardson, Boboz, Holland, Res. Comm. Chem. Pathol. Pharmac. 27, 497, 1980). Displacement of 50% of acridine orange from calf thymus DNA was obtained with 0.18 micro M of NSC 287836 while 0.52 micro M of NSC 287513 was needed to displace an equivalent amount of acridine orange. NSC 287513 showed preference for polynucleotides of high adenine + thymine content while NSC 287836 did not. Analogs lacking both hydroxyethylaminoethyl-amino side chains did not displace acridine orange.

Acridine Orange↗
PubMed1982

Quantification of homoharringtonine and harringtonine in serum by chemical ionization mass spectrometry.

Homoharringtonine and harringtonine are esters of cephalotaxine and are naturally occurring alkaloids in certain coniferous trees in China. These compounds have been shown to have activity against certain types of leukemia in cell cultures, experimental animals, and initial clinical trials in China, and will undergo Phase I trials in several institutions. A gas chromatographic mass spectrometric technique was developed for the quantification of both drugs in serum. One drug serves as internal standard for the other. The drugs are extracted from serum with dichloromethane and are quantified by monitoring the protonated molecular ions of the trimethylsilyl derivatives obtained by chemical ionization (methane). Masses monitored are: m/z = 690 for homoharringtonine and m/z = 676 for harringtonine. Detection limit: 10 ng ml-1 (20 nmol); reproducibility: 1.6-15.0% in the 0-200 ng ml-1 range. Serum levels of harringtonine reached 145 ng mg-1 upon intraperitoneal injection of 3 mg kg-1 in BDF-3 mice.

Alkaloids↗