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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1990

Leaf Senescence in a Nonyellowing Mutant of Festuca pratensis: Metabolism of Cytochrome f.

In a mutant genotype of Festuca pratensis Huds., net degradation of a number of thylakoid membrane proteins during senescence is impaired. Previous studies have suggested that the highly hydrophobic intrinsic chlorophyll-binding proteins were the definitive subjects of the metabolic lesion. In the present study we find that cytochrome f, as determined by haem-staining, Western blotting, enzyme-linked immunosorbent assay, and immunogold electron microscopy, is also abnormally stable in the mutant. The structural feature common to all the proteins in the mutant so far recognized to be abnormally stable is possession of a tetrapyrrole prosthetic group. It is suggested that degradation of chlorophyll and haem may regulate degradation of the associated apoproteins, and hence has an important role to play in membrane protein turnover and in mobilisation of amino acids during chloroplast disassembly.

Journal Article↗
PubMed1990

Toxicological implications of enzymatic control of reactive metabolites.

Many foreign compounds are transformed into reactive metabolites, which may produce genotoxic effects by chemically altering critical biomolecules. Reactive metabolites are under the control of activating, inactivating and precursor sequestering enzymes. Such enzymes are under the long-term control of induction and repression, as well as the short-term control of post-translational modification and low molecular weight activators or inhibitors. In addition, the efficiency of these enzyme systems in preventing reactive metabolite-mediated toxicity is directed by their subcellular compartmentalization and isoenzymic multiplicity. Extrapolation from toxicological test systems to the human requires information of these variables in the system in question and in man. Differences in susceptibility to toxic challenges between species and individuals are often causally linked to differences in these control factors.

Base Sequence↗
PubMed1990

Rat and human liver cytosolic epoxide hydrolases: evidence for multiple forms at level of protein and mRNA.

Two forms of human liver cytosolic epoxide hydrolase (cEH) with diagnostic substrate specificity for trans-stilbene oxide (cEHTSO) and cis-stilbene oxide (cEHCSO) have been identified, and cEHCSO was purified to apparent homogeneity. The enzyme had a monomer molecular weight of 49 kDa and an isoelectric point of 9.2. Pure cEHCSO hydrolyzed CSO at a rate of 145 nmole/min/mg. TSO was not metabolized at a detectable level, and like cEHTSO, the enzyme was about three times more active at pH 7.4 than at pH 9.0. Unlike cEHTSO, cEHCSO was efficiently inhibited by 1 mM 1-trichloropropene oxide (90.5%) and 1 mM STO (92%). Similarly, liver cEH purified 541-fold from fenofibrate induced Fischer 344 rats was shown to be a native 120 kDa dimer of two 61 kDa subunits. The enzyme expressed maximum activity of 205 nmole/min/mg at pH 7.4 toward the diagnostic substrate TSO with an apparent Km of 1.7 microM. In Western blots, polyclonal antibodies against rat liver cEH were shown to recognize a single 61 kDa protein band from liver cytosol of rat, mouse, guinea pig, Syrian hamster, and rabbit. This antibody precipitated neither human liver cEHTSO or cEHCSO. Antibodies against rat liver microsomal epoxide hydrolase reacted with cEHCSO in the Western blot and on immunoprecipitation. Using antibodies against rat liver cEH, 24 positive clones were picked upon colony blot screening of a pEX 1/E. coli POP 2136 expression library.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mass spectrometric peptide mapping analysis and structural characterization of dihydrodiol dehydrogenase isoenzymes.

The direct molecular weight determination and structural analysis of polypeptides and peptide mixtures have become amenable by the recent development of fast atom bombardment (FABMS) and 252Cf-plasma desorption (PDMS) mass spectrometry. FABMS and PDMS peptide mapping, i.e., the direct analysis of peptide mixtures resulting from proteolytic digestion, have been developed as powerful methods for the structural characterization of epoxide-metabolizing isoenzymes. The major advantage of this approach is provided by the selectivity of the endoproteolytic cleavage, combined with the specific and accurate molecular weight determination of complex digest mixtures containing peptides up to several thousands daltons in size. Furthermore, the mass spectrometric peptide mapping analysis can be combined with a range of protein-chemical modification reactions and with sequential degradation such as by carboxypeptidases. Both FABMS and PDMS peptide mapping have already been successfully applied to the structural differentiation of glutathione transferase and epoxide hydrolase isoenzymes in cases where references sequence data for at least one isoenzyme form was available. In the application described here, for a series of dihydrodiol dehydrogenase (DDH) isoenzymes with hitherto undetermined primary structures, a direct correlation between the structural differentiation from peptide mapping data and differences in their substrate specificities could be demonstrated. The mass spectrometric peptide mapping analysis of isoenzymes proved to be an efficient basis for the elucidation of the structure of one major DDH isoenzyme form; partial sequence data for this protein are reported.

Alcohol Oxidoreductases↗
PubMed1989

The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells.

The distribution and inducibility of cytosolic glutathione S-transferase (EC 2.5.1.18) and glutathione peroxidase (EC 1.11.1.19) activities in rat liver parenchymal, Kupffer and endothelial cells were studied. In untreated rats glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene and 4-hydroxynon-2-trans-enal as substrates was 1.7-2.2-fold higher in parenchymal cells than in Kupffer and endothelial cells, whereas total, selenium-dependent and non-selenium-dependent glutathione peroxidase activities were similar in all three cell types. Glutathione S-transferase isoenzymes in parenchymal and non-parenchymal cells isolated from untreated rats were separated by chromatofocusing in an f.p.l.c. system: all glutathione S-transferase isoenzymes observed in the sinusoidal lining cells were also detected in the parenchymal cells, whereas Kupffer and endothelial cells lacked several glutathione S-transferase isoenzymes present in parenchymal cells. At 5 days after administration of Arocolor 1254 glutathione S-transferase activity was only enhanced in parenchymal cells; furthermore, selenium-dependent glutathione peroxidase activity decreased in parenchymal and non-parenchymal cells. At 13 days after a single injection of Aroclor 1254 a strong induction of glutathione S-transferase had taken place in all three cell types, whereas selenium-dependent glutathione peroxidase activity remained unchanged (endothelial cells) or was depressed (parenchymal and Kupffer cells). Hence these results clearly establish that glutathione S-transferase and glutathione peroxidase are differentially regulated in rat liver parenchymal as well as non-parenchymal cells. The presence of glutathione peroxidase and several glutathione S-transferase isoenzymes capable of detoxifying a variety of compounds in Kupffer and endothelial cells might be crucial to protect the liver from damage by potentially hepatotoxic substances.

Animals↗
PubMed1989

Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal beta-oxidation.

The activities of peroxisomal beta-oxidation, cytosolic and microsomal epoxide hydrolase as well as soluble glutathione S-transferases have been determined in the livers of alloxan- and streptozotocin-diabetic male Fischer-344 rats. Five, seven and ten days after initiation of diabetes serum glucose levels were elevated 3.6-, 5.7- to 6.2- and 6-fold, while the activities of peroxisomal beta-oxidation and cytosolic epoxide hydrolase were elevated 1.5- and 2.5-fold, 1.4- and 2.7-fold and 1.3- and 2.0-fold, respectively. The activities of microsomal epoxide hydrolase and glutathione S-transferases were reduced to about 71% and 80% of controls. Application of 10 I.U./kg depot insulin twice a day for 10 consecutive days to alloxan-diabetic individuals approximately restored the initial glucose levels and enzyme activities except for peroxisomal beta-oxidation. Starvation of Fischer-344 rats for 48 hours and 5 days similarly resulted in a 1.3-fold to 2.1-fold and 1.2- to 1.6-fold increase in peroxisomal beta-oxidation and cytosolic epoxide hydrolase activity, respectively. Microsomal epoxide hydrolase was significantly decreased to 57% and 61% of control activity whereas glutathione S-transferase was only marginally reduced to 91% and 92%. Except for glutathione S-transferases initial enzyme activities were restored upon refeeding within 10 days. These results are similar to those obtained upon feeding of hypolipidemic compounds with peroxisome proliferating activity, and may indicate that high levels of free fatty acids or their metabolites which are known to accumulate in liver in both metabolic states may act as endogenous peroxisome proliferators.

Animals↗
PubMed1989

Effect of hypolipidemic compounds on lauric acid hydroxylation and phase II enzymes.

Treatment of male Fischer 344 rats with various hypolipidemic drugs of different peroxisome proliferating potency (1-benzylimidazole, acetylsalicylic acid, clofibrate, tiadenol) led to an induction of liver lauric acid hydroxylase, whereas probucol, which is not a peroxisome proliferator, did not induce this enzyme. Activity of bilirubin UDP-glucuronosyltransferase was increased by all the compounds tested. The highest increase was observed after treatment with acetylsalicylic acid (2.3-fold). High correlation (r = 0.953) was observed between the activities of lauric acid hydroxylase and the corresponding activities of cytosolic epoxide hydrolase reported previously. The amount of microsomal epoxide hydrolase was not changed by any of the compounds. Whereas clofibrate and tiadenol decreased glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as substrate, 1-benzylimidazole and probucol increased this activity. With 4-hydroxynonenal as a substrate qualitatively the same results were obtained with the exception that probucol did not affect the enzyme activity. When glutathione S-transferase activity was measured with cis-stilbene oxide as substrate only the more than five-fold increase after treatment with 1-benzylimidazole was significantly different from control values. Activity of dihydrodiol dehydrogenase was increased after treatment of rats with 1-benzylimidazole (1.5-fold), whereas application of tiadenol led to a decrease of enzyme activity. Feeding of male guinea pigs with clofibrate did not change the activity of peroxisomal beta-oxidation, cytosolic epoxide hydrolase or lauric acid hydroxylase. However, treatment with tiadenol caused an increase of these activities.

Animals↗
PubMed1989

Valpromide is a poor inhibitor of the cytosolic epoxide hydrolase.

The effect of the antiepileptics valpromide and sodium valproate on the cytosolic epoxide hydrolase was studied in human fetal liver, kidneys and adrenals and from human adult liver and kidneys. Trans-stilbene oxide was used as substrate. Valpromide (10 mM) lowered the activity of the epoxide hydrolase to one half of the control in all organs studied. Sodium valproate (10 mM) was less powerful as an inhibitor than valpromide; however, it exerted a significant inhibition in all tissues studied.

Anticonvulsants↗
PubMed1989

A pharmacological evaluation of a new 3-month depot preparation of buserelin for prostatic cancer.

A new slow-release formulation of buserelin given as a 3-month depot injection was evaluated in four patients with advanced prostatic cancer. Treatment was maintained for a mean period of 15 months. Steady-state urinary buserelin concentrations were reached by the beginning of the 3rd week of treatment and maintained until the end of the 3rd month. Serum testosterone remained suppressed in the castrate range for the duration of the study. This preparation offers an advantage for the patient and clinician over existing methods of gonadotrophin-releasing hormone (GnRH) analogue administration and will enter further clinical trial.

Buserelin↗
PubMed1989

The effect of the 1979 French seat-belt law on the nature and severity of injuries to front-seat occupants.

In a regional study of the effect of the 1979 French seat-belt law, the nature and severity of car occupants' injuries were recorded for all car crashes during the same 3-month period in 1976, 1977, 1978 (before the law), and in 1979 (after the law). A trend analysis of data from all 4 years showed a slight decrease in the total injury rate, and significant decreases in the frequency of hospital admissions, and of head, face, arm, and leg injuries. Moderate pelvic and leg injuries, and serious head injuries were also less than expected in 1979. There was also a significant increase in the frequency of thoraco-lumbar spine injuries and of serious cervical spine injuries, but the absolute increase in these injuries was less than the absolute decrease in other injuries. These changes are compatible with the biomechanical effects of increased seat belt use, and thus suggest a beneficial effect of the law.

Accidents, Traffic↗
PubMed1989

Malignant ascites: review of the literature, and an update on monoclonal antibody-targeted therapy.

Malignant ascites presents a difficult clinical problem, causing discomfort and distress to patients in the later stages of disease. Repeated attempts at palliation are often unsuccessful. In this article, conventional forms of therapy for malignant ascites are reviewed and their limitations outlined. Furthermore, we present data on a new form of therapy: antibody guided irradiation. Pilot studies have produced encouraging results in the management of malignant serous effusions, and further randomised studies are currently in progress.

Antibodies, Monoclonal↗
PubMed1989

Kinetic implications of structural modification in protein turnover.

It is thought that an important function of protein turnover is to purge the cell of damaged, displaced or unwanted polypeptide molecules. A model combining kinetic equations for synthesis, degradation and alteration is employed to evaluate this proposed role for protein turnover. It is demonstrated that the degradative system need not be aimed exclusively at altered protein molecules for turnover to be capable of controlling the size both of the total population and of the altered subpopulation. These conclusions are relevant to the part played by turnover in metabolic homeostasis, adaptation and catastrophe, and for the notion of control of protein turnover through specific "tagging" of molecules destined for breakdown.

Data Interpretation, Statistical↗
PubMed1989

Research on predictability in cephalometry of the relationship of chin symphysis and nose-chin balance.

A sample of 120 untreated Caucasian adults was selected. All subjects were dental and skeletal Class I. The approach calls for the use of an original cephalometric method that is applied to the cutaneous profile by an esthetic curve extending from the nose to the chin. Statistical study of the sample confirms the existence of this cutaneous profile, regardless of facial type. This approach is proposed in combination with Sassouni's analysis to specify pogonion in the vertical and anteroposterior planes from which the vertical position of the chin (menton) may be deduced.

Adult↗