Biomedical subjects

H J Rogers

Publications and source records attributed to H J Rogers.

At least 37 records · Page 2Linked to original sources

PubMed1992

The role of Eh, pH and iron in the bactericidal power of human plasma.

The bactericidal power of fresh human plasma against Klebsiella pneumoniae and Escherichia coli was extremely sensitive to changes in Eh and pH. At a high Eh (approx. +200 mV) the bacteria were destroyed, but rapid regrowth occurred when the Eh was lowered to approx. -400 mV. Abolition of the bactericidal effect was also produced by adding ferric iron at a high Eh (approx. +200 mV). Lowering the pH to 6.50 reduced or prevented the bactericidal effect. These results are probably related to the availability of iron for bacterial growth, and could be important for understanding the development of infection in injured or diseased tissue.

Blood Bactericidal Activity↗

PubMed1992

Isolation and characterization of a tobacco gene with homology to pectate lyase which is specifically expressed during microsporogenesis.

A genomic clone has been isolated which contains an open reading frame of 1191 bp interrupted by two small introns. The ORF has been sequenced and the transcriptional start determined. The predicted amino acid sequence shows homology to the deduced amino acid sequences of two pollen-specific pectate lyase genes identified in tomato. The genomic clone was isolated using a partial cDNA clone, TP10, which had been isolated from a Nicotiana tabacum pollen cDNA library by means of differential screening. TP10 has been fully sequenced and contains an open reading frame of 792 bp which shows 96% homology to the ORF in the genomic clone. The transcript corresponding to TP10 is maximally expressed late in pollen development, and has not been detected in vegetative tissues.

Amino Acid Sequence↗

PubMed1992

Uroepithelial and nephrotubular toxicity in patients receiving ifosfamide/mesna: measurement of urinary N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin.

The effect of three ifosfamide/mesna regimens on urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and beta-2-microglobulin (beta 2 M) was studied. All regimens produced significant increases in these urinary proteins, indicating nephrotubular damage. In regimen A (n = 15), plasma nitrobenzylpyridine (NBP) alkylating activity area under the curve (AUC) on day 1 correlated with the percentage increase above baseline of maximum urinary NAG activity (r2 = 0.538, P = 0.0022) and maximum beta 2 M concentration (r2 = 0.413, P = 0.0097). In regimen B (n = 5), plasma NBP alkylating activity AUC correlated with the percentage increase above baseline of maximum NAG activity (r2 = 0.843, P = 0.03) and beta 2 M (r2 = 0.78, P = 0.046). In these two regimens the renal exposure to ifosfamide metabolites correlated with the increases in urinary NAG and beta 2 M. The relation of these urinary protein abnormalities to longer term effects on renal function with different ifosfamide/mesna schedules requires further study.

Acetylglucosaminidase↗

PubMed1992

Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV-seropositive homosexual men.

Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors.

Adolescent↗

PubMed1991

Pollen specific cDNA clones from Zea mays.

We have cloned and sequenced four pollen-specific cDNAs. None of the clones are complete at their 5' ends. One of the clones shows significant homology to the tomato fruit-ripening polygalacturonase and to a pollen-specific polygalacturonase from Oenothera. The other three clones have no significant homologies to any reported sequence.

Amino Acid Sequence↗

PubMed1991

The critical role of iron in some clinical infections.

The role of iron in certain clinical infections is revealed. In normal persons the antibacterial and antifungal properties of blood and other tissue fluids cannot be maintained unless there are exceptionally low levels of available iron. This is controlled by the presence of the unsaturated iron-binding proteins, transferrin and lactoferrin. In several clinical conditions an abnormal availability of iron is responsible for fatal septicaemia. This is because the phagocytic system is overwhelmed by rapidly growing organisms when iron is freely available.

Bacterial Infections↗

PubMed1991

The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.

1. We investigated the pharmacokinetics of ifosfamide 5 g m-2 given by two regimens. Six patients (one female), median age 55 (range 40-71) years, all with lung cancer received 5 g m-2 ifosfamide (median ifosfamide dose 8.95 g) as an intravenous infusion over 0.5 h with mesna. Four other cancer patients (all male) of median age 52.5 (range 23-72) years were studied on seven treatment occasions with 5 g m-2 ifosfamide (median ifosfamide dose 8.88 g) as a 24 h intravenous infusion with mesna. Plasma was assayed for ifosfamide by gas liquid chromatography and for alkylating activity by the nitrobenzylpyridine method. 2. After ifosfamide 5 g m-2 infused over 0.5 h, the decay of the plasma ifosfamide concentration was monoexponential with a median (range) t1/2,z of 5.4 h (3.6-10.4 h). The median clearance was 60 ml min-1 (47-104) and the median volume of distribution was 388 (329-783) ml kg-1. Plasma nitrobenzylpyridine alkylating activity showed a biexponential decay in four patients and a monoexponential decay in two, with a median AUC of 102 (24-177) nmol nor nitrogen mustard eq h ml-1. 3. When ifosfamide 5 g m-2 was given as a 24 h infusion, the decay of the plasma ifosfamide concentration was monoexponential, the median (range) t1/2,z was 4.5 (3.4-6.1), the median volume of distribution was 563 (292-818) ml kg-1 and the median clearance was 79 (59-116) ml min-1. Plasma nitrobenzylpyridine alkylating activity decayed monoexponentially and the median AUC was 49 (45-131) nmol nor nitrogen mustard eq ml-1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Intracellular location of the autolytic N-acetylmuramyl-L-alanine amidase in Bacillus subtilis 168 and in an autolysis-deficient mutant by immunoelectron microscopy.

Antisera against purified autolytic N-acetylmuramyl-L-alanine amidase from Bacillus subtilis 168 were prepared in rabbits. They neutralized the enzymatic action of the purified amidase acting on isolated sodium dodecyl sulfate (SDS)-treated walls from the same organism. They also inhibited the lysis of native walls, but only after the walls lysed partially. Amidase adsorbed to insoluble walls still combined with antibody. Antisera did not stop the lysis of whole cells. Lowicryl HM20 sections of both strain 168 and its autolytic mutant strain FJ6 were prepared by the progressive-lowering-of-temperature technique, immunolabeled with the antisera, and visualized with colloidal gold particles as markers. The highest concentration of gold particles seemed to be in the septa of dividing cells, followed by the side walls. There was some labeling of the cytoplasm. Adsorption of sera with SDS-treated walls reduced the overall labeling of sections considerably but did not alter the relative intracellular distribution of particles. The results for strains 168 and FJ6 were similar. Labeling of SDS-treated walls unexpectedly revealed the presence of a wall-bound amidase fraction.

Antibodies, Bacterial↗

PubMed1990

Iron, infection, and the role of bicarbonate.

Ferric iron will not saturate transferrin in Tris buffer, and its use in experimental infections has been criticized. However, in the presence of bicarbonate, as in plasma, saturation occurs rapidly. This is comparable to natural iron overload, and infections.

Bacterial Infections↗

PubMed1990

Fractionated ifosfamide therapy produces a time-dependent increase in ifosfamide metabolism.

1. Fifteen patients received 1.5 g m-2 of ifosfamide intravenously over 0.5 h every day for 5 days. Twenty-one courses of treatment were studied. Plasma was assayed for ifosfamide by gas liquid chromatography and plasma alkylating activity was measured using the nitrobenzylpyridine (NBP) reaction. 2. A pharmacokinetic analysis revealed a significant decrease in the median (range) elimination half-life of ifosfamide from 7.2 (2.8-14.2) h on day 1 to 4.6 (2.3-7.7) h on day 5 (P less than 0.001, Wilcoxon's test) with a concomitant significant increase in the median (range) clearance from 66 (31-148) ml min-1 on day 1 to 115 (52-381) ml min-1 on day 5 (P less than 0.001). There was no significant change in the volume of distribution on day 5 compared with day 1. 3. There was a highly significant 223% increase in the median (range) plasma nitrobenzylpyridine alkylating activity area under the curve on day 1 from 16 (0.6-105) nmol nor nitrogen mustard equivalents ml-1 h to 52 (13-238) nmol nor nitrogen mustard equivalents ml-1 h on day 5. 4. During five courses of treatment (in five patients in the group) 24 h urine samples were collected on days 1 and 5. The median (range) renal clearance of ifosfamide on day 1 was 6.8 (1.3-16.2) ml min-1 compared with 5.7 (1.3-15.3) ml min-1 on day 5. This difference was not significant. The median (range) metabolic clearance of ifosfamide in these five patients on day 1 was 78.6 (39.9-141.2) ml min-1 and 132.6 (54.6-149.5) ml min-1 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1989

Urinary excretion of prednisolone following intravenous administration in humans.

The urinary excretion of prednisolone was studied in eight normal human volunteers (two women and six men) following intravenous (16, 32, 48 and 64 mg) doses. Urine prednisolone concentrations were determined by a high performance thin layer chromatographic method (HPTLC). The overall mean prednisolone elimination half life in urine following all the intravenous doses as determined by the rate and sigma minus plots was 1.13 +/- 0.25 hour. This was independent of dose and shorter than that found in plasma (4.10 +/- 1.00 s.d. hour). The overall mean percentage of dose excreted unchanged in urine was 16.7 +/- 5.8% following all intravenous and oral doses respectively. About 80% of this amount was excreted within the first 4 hours of the intravenous administration. Renal clearance of prednisolone decreased with time by the first order kinetic (r = 0.790) and its overall value following all IV doses was 0.0183 +/- 0.0103 (s.d.) l/h/kg. The metabolic clearance remained constant with increasing doses from 16 to 64 mg (0.0883 +/- 0.0306 s.d. l/h/kg). From this study it was concluded that a definitive account of the renal elimination of prednisolone and its possible metabolites warrant further investigation. The fraction of the dose excreted unchanged was relatively small and variable suggesting that prednisolone elimination occurs mainly by metabolism.

Adult↗

PubMed1989

Two chromatographic methods for the determination of corticosteroids in human biological fluids: pharmacokinetic applications.

Two techniques, high-performance liquid chromatography (HPLC) and quantitative high-performance thin-layer chromatography coupled with densitometry (HPTLC), were developed for the determination of prednisolone (PL), methylprednisolone (MP), and methylprednisolone sodium succinate (MPSS) in human plasma, saliva, and urine. The HPLC and HPTLC methods shared a single and simple step of an organic extraction procedure and separation of steroids using a normal-phase column or HPTLC plate. The methods allow simultaneous measurement of endogenous cortisol in plasma following the administration of PL and MP. The calibration curves of steroids in all biological fluids were linear over a wide range of concentrations of PL and MP in all biological fluids (0.025-4 micrograms/mL). The limit of detection of both assays for PL and MP was 10 ng/mL in plasma and saliva and 25 ng/mL in urine, and of MPSS was 50 ng/mL in plasma. Both methods were reproducible with an inter- and intra-assay coefficient of variation of less than 10% for all steroids over a wide range of concentrations in all biological fluids. No interference from endogenous steroids was found. The presented methods are simple, rapid, specific, sensitive, reproducible, and economical for the pharmacokinetic study of these steroids. The application of these methods for the pharmacokinetic study of both MP and PL in vivo and the in vitro hydrolysis of MPSS is discussed.

Adrenal Cortex Hormones↗

PubMed1989

Effect of cancer chemotherapy on dapsone N-acetylation in man.

The effect of cancer chemotherapy on dapsone (DDS) N-acetylation was explored in 28 patients with various malignancies. There was a significant (P = 0.01) increase in plasma monoacetydapsone/dapsone (MADDS/DDS) ratios within 24 h of the start of chemotherapy (CT), indicating an acceleration of N-acetylation.

Acetylation↗

PubMed1989

The influence of cimetidine on debrisoquine 4-hydroxylation in extensive metabolizers.

We have studied the effect of cimetidine (800 mg.day-1) administration for three days on debrisoquine 4-hydroxylation in nine healthy extensive metabolizers. The debrisoquine metabolic ratio was significantly increased (p less than 0.01), but the new ratios remained in the extensive metabolizer range (less than 12.6). These data suggest that pre-treatment with cimetidine in usual therapeutic doses will impair debrisoquine 4-hydroxylation, but not enough to alter the apparent oxidation phenotype.

Adult↗

PubMed1989

Effect of food on the absorption and pharmacokinetics of prednisolone from enteric-coated tablets.

Prednisolone absorption and bioavailability of 10 mg enteric-coated (EC) and plain (uncoated) tablets were investigated after fasting and heavy meals (EC only) consumed to satiety in normal healthy volunteers. The same volunteers had also received 16 mg of prednisolone intravenously. In fasted subjects, the absolute bioavailability fraction, as normalised for intravenous doses, of prednisolone from plain tablets was 1.055 and from EC tablets was 0.996. The peak concentrations after plain and EC tablets were 309 and 249 ng/ml attained at 0.98 and 5.14 h, respectively. The means plasma elimination half-lives following the plain, EC tablets and intravenous administration in fasting conditions were 3.73, 3.89 and 3.78 h, respectively. Food interfered with both the absorption and the pharmacokinetics of prednisolone after EC tablets resulting in variability in its plasma levels. In some cases absorption of prednisolone was delayed for 12 h and remained at a measurable level for 24 h. In other cases, a normal absorption pattern was observed. This inter- and intrasubject variability of the effect of food appears to be related to its quantity, constituents and also the subjects physiological characteristics. It is concluded that enteric-coated prednisolone tablets should be administered at least 2 h between meals. However, for more predictable corticosteroid absorption (perhaps thus avoiding the therapeutic failure), plain prednisolone tablets are preferable.

Adult↗

PubMed1989

Methylprednisolone pharmacokinetics after intravenous and oral administration.

1. The pharmacokinetics of methylprednisolone (MP) were studied in five normal subjects following intravenous doses of 20, 40 and 80 mg methylprednisolone sodium succinate (MPSS) and an oral dose of 20 mg methylprednisolone as 4 x 5 mg tablets. Plasma concentrations of MP and MPSS were measured by both high performance thin layer (h.p.t.l.c.) and high pressure liquid chromatography (h.p.l.c.). 2. The mean values (+/- s.d.) of half-life, mean residence time (MRT), systemic clearance (CL) and volume of distribution at steady state (Vss) of MP following intravenous administration were 1.93 +/- 0.35 h, 3.50 +/- 1.01 h, 0.45 +/- 0.12 lh-1 kg-1 and 1.5 +/- 0.63 1 kg-1, respectively. There was no evidence of dose-related changes in these values. The plasma MP concentration-time curves were superimposable when normalized for dose. 3. The bioavailability of methylprednisolone from the 20 mg tablet was 0.82 +/- 0.11 (s.d.). 4. In vivo hydrolysis of MPSS was rapid with a half-life of 4.14 +/- 1.62 (s.d.) min, and was independent of dose. In contrast, in vitro hydrolysis in plasma, whole blood and red blood cells was slow; the process continuing for more than 7 days. Sodium fluoride did not prevent the hydrolysis of MPSS.

Administration, Oral↗

PubMed1988

Ifosfamide plasma clearance in relation to polymorphic debrisoquine oxidation.

Ifosfamide (IF) pharmacokinetics and the plasma (NBP)-alkylating activity were determined in 33 patients with different tumours after the administration of IF as single-agent chemotherapy. All subjects had been phenotyped for debrisoquine oxidation. There is a lack of correlation between the debrisoquine metabolic ratio (DMR) and either the total plasma clearance of IF (CLIF) or the AUC of the plasma NBP-alkylating activity.

Adult↗

PubMed1988

Polymorphic N-acetylation capacity in lung cancer.

Hepatic N-acetylation phenotype has been suggested to be an important risk factor in the aetiology of bladder cancer. This study explores the N-acetylation capacity of a series of lung cancer cases (126) and two control groups. No overall association of slow or rapid acetylators exists between cancer patients and controls. There is also no difference in the distribution of acetylation phenotypes amongst the histological subtypes.

Acetylation↗