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Biomedical subjects

L A Wheeler

Publications and source records attributed to L A Wheeler.

At least 73 records · Page 4Linked to original sources
PubMed1979

Transformation of 4-androsten-3,17-dione by growing cultures and cell extracts of Clostridium paraputrificum.

Growing cultures of Clostridium paraputrificum transformed 4-androsten-3,17-dione to 3 alpha-hydroxy-5 beta-androstan-17-one in a sequential manner with 5 beta-androstan-3,17-dione as an intermediate. The addition of 1.5 mM menadione to log-phase cultures which had formed 5 beta-androstan-3,17-dione resulted in a partial reoxidation of this steroid to 4-androsten-3,17-dione. However, this treatment also resulted in transient inhibition of culture growth. Resumption of growth was accompanied by complete reduction of 4-androsten-3,17-dione to 5 beta-androstan-3,17-dione. Cell extracts of C. paraputrificum were capable of carrying out these reductive transformations in the absence of added cofactors. However, Sephadex G-25 treated extracts required NADH or NADPH for these reactions. A flavin nucleotide, either FAD (plus NADH or NADPH) or FMN (plus NADH) was highly stimulatory for 4-androsten-3,17-dione reduction to 5 beta-androstan-3,17-dione. NADH was the preferred reduced pyridine nucleotide for reduction of the C4-C5 double bond, while time-course measurements suggested that NADPH was the preferred donor for reduction of the 3-keto group.

Androstanes↗
PubMed1979

Clinical estimation of creatinine clearance.

One hundred fifty-four 24-hour urine collections from 16 patients with stable renal function from whom careful urine collections were made were used to compare the "error" in determining renal function (creatinine clearance) when it is estimated using measured 24-hour creatinine excretion versus when creatinine excretion is predicted from serum creatinine, sex, age, and weight, using a simple estimation scheme. These "errors" were comparable (the coefficients of variation were 10% and 13%, respectively). Thus, the prediction scheme is as acceptable as direct measurement of creatinine excretion for purposes of estimating creatinine clearance in stable patients, and is simpler to perform. Two hundred twenty-two 24-hour urine collections from 86 patients having urine collections performed in a routine fashion were also analyzed in this manner. The routinely assessed patients demonstrated markedly greater intraindividual variability (coefficient of variation, 27%) in measured creatinine excretion than did the carefully studied patients (10%). The authors suspect that the excess variability was due to inaccurate urine collection. If so, the prediction scheme may also be acceptable in the routine clinical setting.

Adult↗
PubMed1979

The performance of delta check methods.

The percentage of mislabeled specimens detected (true-positive rate) and the percentage of correctly labeled specimens misidentified (false-positive rate) were computed for three previously proposed delta check methods and two linear discriminant functions. The true-positive rate was computed from a set of pairs of specimens, each having one member replaced by a member from another pair chosen at random. The relationship between true-positive and false-positive rates was similar among the delta check methods tested, indicating equal performance for all of them over the range of false-positive rate of interest. At a practical false-positive operating rate of about 5%, delta check methods detect only about 50% of mislabeled specimens; even if the actual mislabeling rate is moderate (e.g., 1%), only abot 10% of specimens flagged a by a delta check will actually have been mislabeled.

Bicarbonates↗
PubMed1978

Use of high-pressure liquid chromatography to determine plasma levels of metronidazole and metabolites after intravenous administration.

A rapid and sensitive high-pressure liquid chromatography assay for metronidazole and its two principle metabolites, 1-(2-hydroxyethyl-2-hydroxymethyl)-5-nitro-imidazole [hydroxy metabolite] and 1-acetic acid-2-methyl-5-metronidazole [acid metabolite], was developed. The retention times observed were 5.7, 3.3, and 4.5 min, respectively. A reverse-phase muC(18) Bondapak column using a solvent system of methanol, acetonitrile, and 0.005 M pH 4 potassium dihydrogen phosphate (4:3:93, vol/vol) was used to achieve separation of the three compounds. Patients receiving metronidazole therapy were given a loading dose of 13.6 mg of drug per kg intravenously over 1 h, followed by a maintenance dose of 1.43 mg/kg per h. The range of metronidazole concentrations observed was 6.8 to 47.5 mug/ml. These levels are well above the minimal inhibitory concentrations of most clinically significant anaerobic bacteria including Bacteroides fragilis. Little of the acid metabolite was observed in the plasma. The concentration of hydroxy metabolite ranged from 1.6 to 16 mug/ml. The latter may represent an additional source of antimicrobial activity since the hydroxy metabolite has approximately 30% the biological activity of metronidazole.

Chromatography, High Pressure Liquid↗
PubMed1977

Clinical laboratory use in the evaluation of anemia.

Follow-up tests ordered on 258 consecutively examined inpatients with low hemoglobin values on admission were analyzed. The appropriateness of the follow-up tests was evaluated by chart review after preselection by an algorithm. When the cause of the anemia was known or was irrelevant in view of the patient's clinical status, the laboratory use was judged to be adequate. Seventy-one percent of patients studied had an adequate follow-up, though 11% had nonindicated tests performed, scored as laboratory overuse. Twenty-four percent had no follow-up, scored as laboratory underuse. Five percent did not have all indicated tests done and had nonindicated tests done, scored as a mixture of underuse and overuse. Potential remedies to correct misuse are discussed.

Anemia↗
PubMed1977

Properties of the Ames Salmonella mutants lodged in the gastrointestinal tract of gnotobiotic rats.

An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germ-free Sprague-Dawley rats is maintained during observations for up to 7 months. The bacteria exceed concentrations of 10(7)/g in the forestomach and exceed concentrations of 10(8)/g in the lower bowel and feces. When carcinogens are ingested, the number of revertants in the feces increases. The ingestion of structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists does not increase the number of revertants in the feces. The numbers of salmonella are increased by the addition of Lactobacillus plantarum and Bacteroides fragilis but the salmonella disappear from the gastrointestinal tract when the rats are conventionalized. With the additional flora, there is a decrease in the number of revertants appearing in the feces in response to a given dose of carcinogen. This decrease may reflect an effect of the flora on the activity of the metabolic pathway responsible for the presence of the ultimate carcinogen or it may simply be an effect on the salmonella mutants themselves.

Animals↗
PubMed1977

The effects of additional flora on the response of salmonella mutants lodged in the gastrointestinal tract.

A histidine auxotroph of Salmonella typhimurium, strain TA1538, will lodge for several months in the gastrointestinal tract of otherwise germ-free rats and of rats additionally associated with bacteria characteristic of the normal flora such as Lactobacillus plantarum and Bacteroides vulgatus. In the presence of the additional flora, the concentration of strain TA1538 is diminished in the stomach but not in the lower gastrointestinal tract or in the feces. Following the ingestion of 2-nitrofluorene, there is an increase in the concentration of revertants in the feces which reflects that observed in the colon and cecum. A dose-response relationship can be demonstrated between the amount of 2-nitrofluorene ingested and the concentration of revertants in the feces. A given dose of 2-nitrofluorene, however, produces fewer revertants in the feces of rats with the additional flora than in the feces of rats associated only with strain TA1538. It is not clear whether the decreased number of revertants in the feces in the presence of the additional flora is a result of metabolic transformations of 2-nitrofluorene by B. vulgatus, which can be demonstrated in vitro, or a result of the displacement of strain TA1538 from the stomach. The rat associated with strain TA1538, or other Ames tester strains, may be useful for detecting carcinogens as mutagens within the gastrointestinal tract and for determining the influence of various constituents of the bacterial flora on the concentration of mutagenic compounds.

Animals↗
PubMed1977

Delta check tables for the Technicon SMA 6 continuous-flow analyzer.

To provide a data base for the establishment of a method to detect potentially incorrect SMA 6 test results, we analyzed 2970 pairs of SMA 6 results. For each test result, as well as for the urea nitrogen/creatinine ratio and the anion gap, we estimated to probability density function of the amount of change since the most recent test of the same type. We made separate estimates for each of three ranges of the current test result and two ranges of time-spacing between the tests. Tables of nonparametric estimates of selected points from each of the six distributions for each test result and calculated quantity were developed. These tables could be used to identify unlikely test results, either manually or with a laboratory computer.

Autoanalysis↗
PubMed1976

Association of Salmonella mutants with germ-free rats: characterization of the reverse mutational response to 2-nitrofluorene.

Salmonella typhimurium strain TA1538 described by Ames, in association with otherwise germ-free rats, colonizes the gastrointestinal tract. The revertants enumerated in the feces of each of these rats varies in a coordinated manner in relation to the day on which the measurement is made. In response to the oral ingestion of a single dose of 2-nitrofluorene, the concentration of revertants in the feces increases and then returns essentially to control values within 6 days. When these rats are challenged repeatedly with a similar oral dose of 2-nitrofluorene the revertent concentration in the feces remains elevated for a progressively longer time. A change in phenotype of strain TA1538 during prolonged association rather than a change in the biology of the rat seems to explain this phenomenon. Firstly, germ-free rats exposed repeatedly to 2-nitrofluorene and then associated with strain TA1538 do not have the prolonged response characteristic of multiple challenges with 2-nitrofluorene. Secondly, strain TA1538 reisolated after several weeks of association with the otherwise germ-free rat shows other alterations such as decreased sensitivity to 2-nitrofluorene in the pour plate assay and a decreased sensitivity to crystal violet. In spite of limitations imposed by these alterations in strain TA1538, it is possible to demonstrate a dose-response relationship between the amount of 2-nitrofluorene ingested and the concentration of revertants in the feces of exposed rats.

Administration, Oral↗
PubMed1975

Association of salmonella mutants with germfree rats: site specific model to detect carcinogens as mutagens.

An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germfree Sprague-Dawley rats is maintained during periods of observation lasting as long as 7 months. The bacteria are found at levels exceeding 10(7) per g in the forestomach and at levels greater than 10(8) per g in the lower bowel and in the feces. Only approximately 10(4) bacteria per g are found in the posterior stomach and in the upper small intestine. The association of the salmonella mutants is maintained when the bacterial association is increased by the addition of other bacteria characteristic of the gastrointestinal flora. Carcinogenic amines, which cause strain TA1538 to revert to histidine independence in Ames' in vitro assays, increase the number of revertants in the feces when fed to the salmonella-associated rats. In contrast, the number of revertants in the feces does not increase when the rats are fed structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists. Sacrifice of rats after feeding the carcinogen 2-nitrofluorene indicates that the number of revertants is increased in the cecum and colon as well as in the feces. The apparent proximity of the bacterial mutagenic response to the location of the tumor response in the colon suggests that the rat associated with the histidine auxotroph may provide a useful model for further investigation of the possible association between bacterial mutagenesis and carcinogenesis within the gastrointestinal tract. In addition, with this model it may be possible to evaluate selectively the effects of various constituents of the flora on the activation of compounds provoking the revertant response.

Animals↗
PubMed1975

The relationship between nitro group reduction and the intestinal microflora.

The capacity of rats to reduce a 25-mg dose of p-nitrobenzoic acid (PNBA) was measured by quantifying the amount of this compound recovered in the urine as p-aminobenzoic acid (PABA) and its conjugates. It was found that germfree rats converted approximately 1% of PNBA to PABA; in conventional rats the conversion was approximately 25%. Various bacteria isolated from the rat cecum were selectively associated with germfree rats and it was demonstrated that these bacteria colonized their gastrointestinal tracts. In assoication with Lactobacillus plantarum, the conversion of PNBA to PABA increased to 3.9%. When these rats were further associated with Clostridium sp. and Streptoccocus faecalis, the conversion increased to approximately 12%. A general correlation was found between the capacity of constituents of the microflora to reduce PNBA in vitro and when associated with the germfree rat. Cecectomy, which removes a substantial portion of the microflora of the rat, decreases the capacity of the conventional rat to reduce PNBA. Similar experiments with p-nitrobenzenesulfonamide indicate that this compound is also largely reduced by the flora. Evidence that the reduction of the nitro group in these compounds is carried out by the intestinal microflora explains previous observations in which the reduction of these compounds in rats did not correlate with the activity of liver enzymes putative for these reactions.

Aminobenzoates↗
PubMed1975

Nutrient menu planning for clinical research centers. Control by computer.

A computer program has been developed for the dietetic service of the Clinical Research Center at the University of Florida. Presently, it is used in menu planning and nutrient analysis for selective, controlled-nutrient diets and for constant diets. The program is able to compute food weights for a patient-selected daily menu which would satisfy up to twenty-three nutrient constraints and which may be optimized with respect to one or more of these. The principal benefit of the program is a saving in the dietetian's time in calculating the nutrient content of the diet and in planning diets with several constrained nutrients. It is also being used as a teaching resource for dietetic interns and dietetic trainees.

Computers↗
PubMed1975

The reduction of N-hydroxy-4-acetylaminobiphenyl by the intestinal microflora of the rat.

The role of the intestinal flora in the conversion of N-hydroxy-4-acetyl-aminobiphenyl (N-OH-AABP) to 4-acetylaminobiphenyl has been examined. This reaction, which reverses the metabolic activation of the parent carcinogen, can be demonstrated in cultures of some bacteria indigenous to the intestinal microflora. These include cultures of Clostridium sp., Clostridium perfringens, Peptostreptococcus productus I, and Bacteroides fragilis ss. thetaiotaomicron and ss. vulgatus. In contrast, cultures of Lactobacillus plantarum and Escherichia coli show little or no capacity for this reaction. The reduction of N-OH-AABP is also carried out by homogenates of liver, kidney, and brain. On a weight basis, the cecal flora is considerably more active in reducing N-OH-AABP than are homogenates of tissues of the gastrointestinal tract. The cecal flora also has a greater activity for reducing N-OH-AABP than the stomach flora, an observation which may relate to the induction of tumors in the forestomach but not in the cecum of rats fed this compound. The products of the metabolism of N-OH-AABP have been compared in germ-free and conventional animals. Glucuronide conjugates of N-OH-AABP are found in the cecal contents and feces only of the germ-free rats, while 4-acetylaminobiphenyl is found in the feces only of conventional rats. These results suggest that the flora, by hydrolyzing glucuronides and reducing N-OH-AABP, may influence the level of metabolities of 4-acetylaminobiphenyl which are critical for carcinogenesis.

Aminobiphenyl Compounds↗
PubMedDate not supplied

Effect of platelet-derived growth factor on rabbit corneal wound healing.

Human recombinant platelet-derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet-derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 microg/ml when compared with control; however, the platelet-derived growth factor-BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet-derived growth factor-BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet-derived growth factor-BB-treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet-derived growth factor exhibited a dose-dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet-derived growth factor is active in the corneal wound healing process.

Journal Article↗