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Biomedical subjects

T E Jones

Publications and source records attributed to T E Jones.

At least 55 records · Page 3Linked to original sources
PubMed1982

Guanosine 5'-monophosphate reductase from Leishmania donovani. A possible chemotherapeutic target.

GMP reductase was highly purified from promastigotes of Leishmania donovani by chromatography on a single DEAE-cellulose column. Bimodal substrate saturation curves resulted in a 1/v versus 1/[GMP] plot that curved downward above 40 microM GMP. The kinetic constants were, therefore, obtained with GMP below this concentration. The K'm for GMP was 21 microM at pH 6.9. The enzyme was very sensitive to activation by GTP. At 20 microM GMP, a maximum of 600% activation occurred at 100 microM GTP. Half-maximal activation occurred at 8 microM GTP. GTP at 100 microM did not affect the K'm for GMP but did increase its V'max by 7-fold. Xanthosine monophosphate (XMP) and IMP analogs served equally well as competitive inhibitors versus GMP. The inhibition by the analogs and the activation by GTP were mutually antagonistic processes. The inhibition by the IMP analogs, allopurinol nucleotide and thiopurinol nucleotide is of chemotherapeutic interest because these compounds were shown previously to be produced in Leishmania from the anti-leishmanial agents allopurinol and thiopurinol. These nucleotides were 100- and 20-fold, respectively, more potent inhibitors of GMP reductase from L. donovani than of the corresponding enzyme from human erythrocytes.

Animals↗
PubMed1981

The predictive value of the serum digoxin concentration in the management of hospitalized patients.

Serum digoxin concentration (SDC) was compared with clinical and ancillary predictors as a guide to adjustment of digoxin dose and as a test for digitalis toxicity in a total of 76 hospitalized patients during a period of 9 months. The mean SDC (3.6 +/- 2.5 nmoles/liter) associated with unexpected discontinuation of therapy was significantly higher (p less than 0.001) than that (1.1 +/- 0.6 nmoles/liter) associated with unaltered digoxin dose, while the mean SDC (0.6 +/- 0.4 nmole/liter) associated with unexpected dose increase was significantly lower (p less than 0.05). There was no significant association between other pharmacokinetic or pharmacodynamic predictors and therapeutic intention. There was a 13% incidence of confirmed digitalis intoxication. The mean SDC (3.6 +/- 1.9 nmoles/liter) of patients presenting and confirmed as digitalis toxic was significantly higher (p less than 0.001) than that (1.4 +/- 0.6 nmoles/liter) involving a situation in which digitalis toxicity could not initially be excluded by other means. The predictive value of an SDC greater than or equal to 2.6 nmoles/liter for toxicity was 80%, and its efficiency for diagnosing both toxicity and nontoxicity was 95%. The SDC was thus shown to be a valid test of digitalis toxicity and to provide extraordinary information enabling the clinician to modulate digoxin therapy precisely.

Cardiovascular Diseases↗
PubMed1980

Non-A, non-B hepatitis in patients receiving blood products.

A group of patients all regularly receiving blood products for a congenital bleeding disorder were investigated for evidence of past infection with hepatitis A and B, and compared with a control group. There was a significantly higher percentage of the test group who had markers of infection with these viruses, and 15 patients had symptoms of hepatitis during the study. The greater number of the test group showing evidence of past hepatitis A infection can only really be explained by acquiring antibody from blood products, especially since none of our patients with hepatitis had hepatitis A and there is evidence that this is not an infection associated with blood products. We conclude that the majority of patients in our study showing symptoms of hepatitis had non-A, non-B hepatitis.

Adolescent↗
PubMed1976

Guanosine monophosphate synthetase from Ehrlich ascites cells. Multiple inhibition by pyrophosphate and nucleosides.

GMP synthetase (xanthosine-5'-phosphate: ammonia ligase (AMP-forming), EC 6.3.4.1) from Ehrlich ascites cells was found to be subject to multiple inhibition by its reaction product, PPi, and some analogs of adenosine. PPi and the nucleoside (N) inhibitors were also capable of individually inhibiting this enzyme. Under no conditions did the inhibition appear to be irreversible or "pseudoinactivating" in nature. The individual inhibition by PPi was competitive with respect to ATP (KI = 0.42 mM). Conversely, in the absence of PPi, the binding of N was noncompetitive with ATP, but shifted to a competitive pattern when PPi was present. Furthermore, with the inhibitors in concert, there was an apparent lowering of the KI values for both inhibitors. This data was consistent with either PPi functioning to tighten the binding of N at a noncatalytic site (positive cooperativity) or with PPi actually opening a second binding site for N in addition to the non-catalytic site. Although this study did not distinguish which of these events was occurring, it did reveal that the intensity of the effect of PPi appeared to be constant. That is, for various N inhibitors with a range of independently determined KI values from 26 to 1650 muM, the ratio of their KI values determined in the absence of PPi to the values determined in the presence of PPi was always 38 +/- 1.

Ammonia↗
PubMedDate not supplied

Effects of doxorubicin on human dental pulp cells in vitro.

There is substantial information concerning the effects of continuous exposure to supratherapeutic or therapeutic concentrations of doxorubicin on human molar pulpal cells; the effects of continuous exposure to subtherapeutic concentrations of this agent are undetermined. To this end, we studied the proliferation of human fibroblasts and pulpal cells and their pattern of mineralized nodule deposition in vitro. Cell proliferation was assessed at 1, 3, 5, and 7 days from populations with either no exposure (control) or exposure to 10(-6)-10(-9) mol/L doxorubicin. Mineralized nodule deposition and calcium-45 incorporation were assessed at 7 and 21 days of culture. Data were compared by factorial ANOVA and a post-hoc Tukey test. 10(-6) and 10(-7) mol/L doxorubicin significantly reduced the total number of viable pulpal cells in cultures from days 1 to 3 (p < 0.05); doxorubicin 10(-6)-10(-9) mol/L significantly inhibited cell proliferation (p < 0.05) and DNA synthesis 5 days after plating (p < 0.001). After 21 days, doxorubicin 10(-6)-10(-8) mol/L significantly decreased calcium-45 incorporation into pulpal cultures (p < 0.001); all dilutions significantly reduced the number of mineralized nodules within the 21-day pulpal cultures (p < 0.05). In addition, all dilutions of doxorubicin significantly inhibited fibroblast cell proliferation and incorporation of [(3)H]thymidine. In contrast, the fibroblast cultures did not produce mineralized nodules, suggesting that the mineralized nodules within the pulpal cell cultures did not result from dystrophic calcification. Thus, exposure to subtheraputic doxorubicin concentrations has potential adverse effects on mineralized tissue formation within the pulp, which could affect the rates of reparative dentin deposition within the tooth pulps of patients receiving this chemotherapeutic agent.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Experience with an albumin-enhanced, 15-minute incubation, emergency crossmatch.

During a 40-month period, an emergency crossmatch procedure using an albumin-enhanced 15 minute incubation indirect antiglobulin technique was evaluated along with a standard procedure for 2,276 patients involving 6,423 units of blood. One hundred-forty unsuspected allo-antibodies were detected during this study, of which 130 were detected by both techniques. In five instances where antibodies were not detected by the emergency technique, the antibodies were not though to be clinically significant.

Blood Banks↗