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Biomedical subjects

S C Harris

Publications and source records attributed to S C Harris.

At least 55 records · Page 3Linked to original sources
PubMed1981

Pyrroline-5-carboxylate reductase in human erythrocytes.

Pyrroline-5-carboxylate reductase, which converts pyrroline-5-carboxylate to proline, has been identified in human erythrocytes. The level of pyrroline-5-carboxylate reductase activity in these cells is comparable to the activity levels of major erythrocyte enzymes. The physiologic function of the enzyme in erythrocytes cannot be related to its function in other tissues, i.e., producing proline for protein synthesis. We examined the kinetic properties of erythrocyte pyrroline-5-carboxylate reductase and compared them to the properties of the enzyme from proliferating cultured human fibroblasts. We found that the kinetic properties and regulation of the erythrocyte enzyme are distinctly different from those for human fibroblast pyrroline-5-carboxylate reductase. These characteristics are consistent with the interpretation that the function of the enzyme in human erythrocytes may be to generate oxidizing potential in the form of NADP+.

Adult↗
PubMed1981

Determination of promethazine in serum by liquid chromatography.

We describe a procedure for the liquid-chromatographic determination of promethazine in low-nanogram concentrations in serum. Triflupromazine is used as the internal standard. The method is based on a single extraction of promethazine from serum with hexane and subsequent derivatization with trichloroethyl chloroformate. Analytical recovery of promethazine is about 90%. The lower limit of detection is 1 microgram/L when a 2.0-mL aliquot of serum is assayed. Our data illustrate the practicability of the method for bioavailability studies after oral or rectal administration of promethazine hydrochloride.

Administration, Oral↗
PubMed1980

Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer.

Thirty-seven patients were enrolled in a randomized prospective study to compare standard surgical therapy for superficial bladder cancer to standard therapy plus bacillus Calmette-Guerin (BCG). Side effects of BCG have been tolerated well and include dysuria in 95 per cent of the patients, urinary frequency in 83 per cent, hematuria in 39 per cent, fever in 22 per cent and nausea in 22 per cent. Of 19 control patients 8 (42 per cent) had recurrent tumors in the followup period, compared to 3 of 18 patients (17 per cent) treated with BCG. One patient treated wih BCG had 2 recurrences, yielding a recurrence rate of 22 per cent in the group receiving BCG compared to 42 per cent in controls. When the incidence of recurrent tumors in matched intervals before and after entry into the protocol is compared, no change in the rate of tumor recurrence (p equals 0.726 chi-square) occurred in controls, whereas tumor recurrences were reduced significantly in the group treated with BCG (p equals 0.010 chi-square). The reduction in tumor recurrence in patients treated with BCG compared to controls is statistically significant (p equals 0.029 chi-square). Of 4 patients who presented with new bladder tumors remain free of tumor after BCG therapy, while 2 of 5 comparable control patients developed recurrent tumors. Intravesical and percutaneous BCG immunotherapy appears to decrease the rate of tumor recurrence in patients followed for 1 year.

Aged↗
PubMed1980

Evaluation of an enzyme immunoassay for determining diazepam and nordiazepam in serum and urine.

We evaluated a commercially available enzyme immunoassay method for determining the concentration of total diazepam plus its active metabolite, nordiazepam, in small amounts of serum and urine. The coefficients of variation were 5% within assay and 8% between assay. Concentrations so measured for patients' sera correlated well with those obtained both by gas chromatography with electron-capture detection and by liquid chromatography with ultraviolet detection. For urine samples, the correlation between values obtained by the enzyme immunoassay method and those for total diazepam/nordiazepam/oxazepam obtained by liquid chromatography was adequate for routine clinical toxicological use. The ability of the immunoassay to determine other benzodiazepines was also evaluated.

Chromatography, High Pressure Liquid↗
PubMed1979

Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline.

The initial step in the degradation pathways of proline and hydroxyproline is catalyzed by proline oxidase and hydroxyproline oxidase, yielding delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, respectively. The second step is the oxidation of delta 1-pyrroline-5-carboxylate to glutamate and delta 1-pyrroline-3-hydroxy-5-carboxylate to gamma-hydroxy-glutamate. To determine if this second step in the degradation of proline and hydroxyproline is catalyzed by a common or by separate enzyme(s), we developed a radioisotopic assay for delta 1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity. We then compared delta1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity with that of delta 1-pyrroline-5-carboxylate dehydrogenase in fibroblasts and leukocytes from type II hyperprolinemia patients, heterozygotes, and controls. We found that cells from type II hyperprolinemia patients were deficient in both dehydrogenase activities. Furthermore, these activities were highly correlated over the range found in the normals, heterozygotes, and patients. We conclude from these data that a common delta 1-pyrroline-5-carboxylate dehydrogenase catalyzes the oxidation of both delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, and that this activity is deficient in type II hyperprolinemia.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed1979

Incidence of cocaine metabolites in urine specimens from medical examiners' cases.

Isobutane CIMS is useful for determining the molecular weight of morphine and its derivatives, as well as for identifying labile acyl substituents on morphine's O-6 position. Furthermore, this technique will provide information relating to the presence or absence of pi-bonding on the C-7 carbon. The spectra of morphine derivatives can be further simplified by employing ethylenediamine as a reagent gas. This approach proves useful for eliciting or confirming molecular weight information from the CI spectrum. In our laboratory extended use of ethylenediamine has been accomplished without any deleterious effect on the mass spectrometer's source or its vacuum system. The utility of isobutane and ethylenediamine CI rests with its ability to supply the analyst with structure elucidation data that may be used to complement more detailed information extractable from either EI or CE spectra. This aspect of mass spectrometry is especially useful when one is dealing with an unknown member of a particular class of organic compounds.

Cadaver↗
PubMed1978

Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers.

The authors determined mean day-to-day (daily over five days), mean week-to-week (weekly over five weeks) and mean hour-to-hour (800 h, 1100 h, 1400 h) physiologic intra-individual variation of concentration values of leukocyte cell types, platelet count, and erythrocyte values (hematocrit, hemoglobin) for a group of 20 healthy adult volunteers. Total leukocyte counts and concentration values of leukocyte cell types were determined in duplicate on the Hemalong-DTM Automated Leukocyte Differential Cell Counter to minimize analytic variation. The data sets were analyzed according to an analysis of variance model. The mean physiologic hour-to-hour and week-to-week intra-individual variations in terms of % coefficient of variation included: hemoglobin, 2.5, 2.2; hematocrit, 2.6, 2.7; platelets, 1.6, 6.6; total leukocyte count, 9.4, 15.7; neutrophils, 12.9, 26.0; lymphocytes, 10.3, 13.2; monocytes, 18.6, 19.3; eosinophils, 19.9, 26.9; basophils, 7.4, 15.0; large unstained cells, 13.7, 16.0; "high-peroxidase" cells, 32.7, 25.7. Hour-to-hour variation was partitioned into random diurnal variation, group-consistent diurnal variation, and subject-specific unique individual variation. Subject-specific diurnal variation contributed greatly and statistically significantly to total diurnal variation for many of the leukocyte cell types--especially in the case of eosinophils, where it represented more than half of total diurnal variation.

Adult↗
PubMed1978

Reduction of aspirin-induced gastrointestinal bleeding with cimetidine.

Aspirin induces gastric mucosal damage and bleeding in the presence of acid. Cimetidine, the histamine H2-receptor antagonist, reduces basal and stimulated acid secretion. Arthritic patients taking fixed doses of aspirin who were found to have aspirin-induced occult gastrointestinal bleeding were given cimetidine in a randomized double blind, crossover study. Autologous 51Cr-labeled blood was measured in 4-day stool collections at the end of each 4-week period of placebo and cimetidine therapy in 22 acid-producing patients. Mean daily fecal blood loss was reduced during cimetidine therapy to 2.2 +/- 0.3 ml per day, compared with 4.1 +/- 0.7 ml per day during placebo therapy (P= 0.002).

Arthritis↗
PubMed1978

Lactate dehydrogenase in estrogen-responsive human breast cancer cells.

Lactate dehydrogenase activity (LDH) was measured in the MCF-7 human breast cancer cell line derived at the Michigan Cancer Foundation from a patient with metastatic breast adenocarcinoma. LDH was found in the 46,000 X g supernatant of cell lysates, but not in the culture medium. Only the fifth isozyme (LDH-5) could be demonstrated by cellulose acetate electrophoresis and relative heat inactivation studies. When endogenous steroids were removed from the medium, addition of estrogen to the growth medium for several days elevated LDH 2-fold above controls; LDH was not altered when MCF-7 cells were treated with progesterone, hydrocortisone, prolactin, insulin, or triiodothyronine. A physiological concentration (0.1 nM) of 17beta-estradiol was sufficient to produce a maximal LDH increase. There were no qualitative isozyme changes in response to estrogen. LDH activity may therefore be a useful marker protein for studying hormone action in the MCF-7 human breast cancer cell line.

Adenocarcinoma↗
PubMed1977

Cocaine and benzoylecgonine excretion in humans.

Maximal urinary excretion of unchanged cocaine occurred within 2 h of the intranasal absorption of 1.5 mg/kg body weight of cocaine hydrochloride, and diminished rapidly thereafter. Excretion of benzoylecgonine was maximal 4 to 8 h following administration of the drug and diminished slowly over an interval of several days. Peak cocaine and benzoylecgonine concentrations observed were 24 and 75 microgram/ml, respectively. Benzoylecgonine/cocaine ratios were too varied to allow estimation of cocaine concentrations from benzoylecgonine concentration data or vice versa. Benzoylecgonine concentrations generally exceeded the corresponding cocaine values by a wide margin, but excretion of free cocaine in the absence of benzoylecgonine was observed in one subject. Cocaine was generally detected for only approximately 8 h, and for a maximum of 12 h, whereas benzoylecgonine was generally detected by chromatographic or enzyme immunologic assays for 48 to 72 h. Benzoylecgonine was positively identified in urine by raidoimmunoassay for 96 to 144 h after dosing.

Adult↗
PubMed1977

Bacillus Calmette-Guérin and dinitrochlorobenzene immunotherapy of chemically induced bladder tumors.

Immunologic incompetence is correlated with increased susceptibility to malignacy. Immunostimulation with such agents as Bacillus Calmette-Guérin (BCG) and dinitrochlorobenzene (DNCB) have resulted in regression of cutaneous maligancies. An evaluation of the effect of BCG and dinitrochlorobenzene sensitization and bladder irrigation in Fischer rats revealed no decrease in the incidence of bladder tumors induced by 2-formylamino-4-(5-nitro-2-furyl) thiazole (FANFT). However, direct intralesional injection of BCG into early bladder tumors was effective in preventing the progression of such tumors in seven of ten BCG-sensitized rats (P less than 0.005). No effect was seen when BCG was injected intralesionally in unsensitized rats or when control solutions were injected.

Animals↗