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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 145 records · Page 8Linked to original sources
PubMed1995

In vitro LAK (lymphokine activated killer) activity following autologous peripheral blood stem cell is significantly greater than that following autologous bone marrow and allogeneic bone marrow transplantation.

LAK activity is known to increase following autologous and allogeneic bone marrow transplant and peripheral blood stem cell transplant (PBSCT). The aim of this study was to directly compare the 3 types of transplant and the LAK activity generated. LAK activity following PBSCT is significantly greater than that following autologous bone marrow transplantation and even allogeneic transplantation up to 8 weeks. The type of killer cells generated is similar for the different types of transplants, with most killing activity following PBSCT due to CD56+ cells, though CD3+ cells also contribute. This study would suggest that attempts to augment the graft-versus-leukaemia effect is more likely to be successful following PBSCT than autologous bone marrow transplantation.

Adolescent↗
PubMed1995

[Exogenous allergic alveolitis: 22 year follow-up of malt worker's lung].

This is a report on a case of exogenous allergic alveolitis or malt workers' lung where no irreversible damage to the lung occurred despite a course of 22 years. The diagnosis was arrived at by means of a re-exposure test at the place of work followed by bronchoalveolar lavage. Reasons are being sought for the failure of all other diagnostic methods to diagnose exogenous allergic alveolitis. The disease is distinguished from the "organic dust toxic syndrome" by differential diagnosis.

Alveolitis, Extrinsic Allergic↗
PubMed1994

Oxygen tension, insulin, and glucagon affect the preservation and induction of cytochrome P450 isoforms in cultured rat hepatocytes.

The role of oxygen tension, insulin, and glucagon on the preservation and induction of cytochrome P450 isoenzyme activities and contents was investigated in rat hepatocytes cultured for 4 days on crude liver membrane fractions at 4 or 13% O2. At 13% O2, three out of six immunochemically analyzed P450 isoenzymes were significantly higher than in 4% O2. Exposure to phenobarbital (PB) from Days 1 to 4 dose dependently increased the protein content and decreased the albumin secretion in 13% O2 cultures only. The maximal induction of P450 isoenzymes CYP2B1/2B2 (20- to 25-fold) and CYP2C6 (6-fold) were found at 0.75 mM PB at both oxygen tensions. In contrast, the highest induction of CYP1A1/1A2 (3-fold), of CYP3A (2-fold), and EROD activity were found with 3 mM PB in 4% O2 cultures. CYP2B-dependent testosterone hydroxylation at positions 16 alpha/beta was elevated to a greater extent in 13% O2 cultures (96-fold at 0.75 mM PB) compared to 4% O2 cultures (42-fold). This activity was affected by the insulin concentrations and the insulin:glucagon ratio. With decreasing insulin concentration (100 to 1 nM) or with increasing insulin:glucagon ratios (1:100-1:0.1), the enzyme activity increased preferentially in 4% O2 cultures. The results of these investigations demonstrate that different tissue oxygen tension modulates the responsiveness of the cultured hepatocytes to the glucoregulatory hormones insulin and glucagon and this modulation results in a altered activity of cytochrome P450 isoforms.

Albumins↗
PubMed1994

Bromopropylate: induction of hepatic cytochromes P450 and absence of covalent binding to DNA in mouse liver.

Oral administration of benzilic acid ester-based acaricide bromopropylate at daily doses of 3, 15, 100, and 300 mg/kg body wt to young adult male Tif:MAGf mice for 14 days caused slightly increased liver weights in the high-dose group. A dose-dependent increase of the microsomal cytochrome P450 content was accompanied by elevated ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, pentoxyresorufin O-depentylase, and total testosterone hydroxylase activities. When compared with mice treated in parallel with the model compounds for hepatic xenobiotic metabolizing enzyme induction, phenobarbitone, and 3-methylcholanthrene, the enzyme activity changes observed with bromopropylate largely equalled those expressed in phenobarbitone-treated mice. Immunochemical studies with monoclonal antibodies against rat liver cytochrome P450 isoenzymes of the gene families 1A, 2B, 3A, and 4A confirmed that bromopropylate is a phenobarbitone-type inducer in the mouse liver. Titration of liver microsomal suspensions with bromopropylate yielded Type I substrate binding spectra. The specific amplitude was increased 1.5-fold when microsomes from bromopropylate-treated mice (300 mg/kg body wt) were used instead of control microsomes, indicating the induction of cytochromes P450 catalyzing the oxidative metabolism of the test compound. Single oral administration of 300 mg/kg body wt [14C]bromopropylate to male mice, without or following pretreatment for 14 days with 300 mg/kg body wt unlabeled bromopropylate, gave no indication for DNA binding of the test compound in the liver. This excludes a genotoxic potential via covalent DNA modification. The results suggest that, in analogy to phenobarbitone, bromopropylate acts as a tumor promotor rather than a tumor initiator in the mouse liver.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1994

The effect of indobufen on the activities of selected rat liver phase I and phase II drug metabolizing enzymes, peroxisomal beta-oxidation and hepatic glutathione status.

Oral administration of indobufen to male rats for three days at daily doses of 5, 10 and 20 mg kg-1 resulted in no changes in liver total glutathione, cytosolic glutathione S-transferases or microsomal epoxide hydrolase. Reduced glutathione appeared slightly diminished to about 84% of control at the highest dose level. Microsomal cytochrome P450-dependent ethoxyresorufin O-de-ethylase and pentoxy-resorufin de-alkylase activities were decreased to 64% (not significantly) and 67% of control at the lowest dose level. 6 alpha- and 7 alpha-Hydroxytestosterone activities were decreased to 67 and 68% of control at the highest dose level. Cyanide-insensitive peroxisomal fatty acid beta-oxidation was increased to 223, 261 and 232% of control at doses of 5, 10, and 20 mg kg-1, respectively. The results obtained in this study are indicative of the action of indobufen as a weak peroxisome proliferator in male rat liver, and suggest a slight but toxicologically insignificant inhibitory action of this drug on microsomal cytochrome P450-dependent enzyme activities.

Animals↗
PubMed1994

Diagnosis of interstitial lung disease by a percutaneous lung biopsy sample.

A percutaneous lung biopsy sample was used to diagnose interstitial lung disease in nine children aged less than 42 months. Fibrosing alveolitis was diagnosed in eight children and Pneumocystis carinii pneumonia in one child. Complications associated with the procedure were minimal and the results of the biopsy sample enabled each child to be treated appropriately.

Biopsy, Needle↗
PubMed1994

Automotive airbag-induced second-degree chemical burn resulting in Staphylococcus aureus infection.

A young woman did not seek emergency treatment after a minor automobile collision as she thought that she had been spared serious injury by the inflation of the driver's-side airbag. She had a benign-looking erythema on her neck which, over the next several days, became a second-degree chemical burn infected with Staphylococcus aureus. The burn and subsequent infection took several weeks to heal and the patient had to endure a prolonged course of antibiotics, nonsteroidal antiinflammatory drugs, and continued irrigation. This case exemplifies why alkali chemical burns from an automotive airbag should be treated aggressively, despite their benign appearance, as they may take several days to evolve. Physicians should be warned that careful follow-up examination of patients seen in the hospital emergency department or in the physician's office is necessary to abate any hidden sequelae. Of course, the opportunity to decrease morbidity is lost if the patient does not seek emergency treatment.

Accidents, Traffic↗
PubMed1993

Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli.

A cDNA of 1992 base pairs encoding the complete rat liver cytosolic epoxide hydrolase has been isolated using a polymerase chain reaction-derived DNA fragment (Arand, M., Knehr, M., Thomas, H., Zeller, H. D., and Oesch, F. (1991) FEBS Lett. 294, 19-22) known to represent the 3'-end of the cytosolic epoxide hydrolase mRNA. Sequence analysis revealed an open reading frame of 1662 nucleotides corresponding to 554 amino acids (M(r) = 62,268). The DNA sequence obtained did not display significant homology to the sequences of microsomal epoxide hydrolase or leukotriene A4 hydrolase or to any other DNA included in the EMBL Data Bank (release 32). On Northern blotting of rat liver RNA, a single mRNA species was detected that was strongly induced on treatment of the animal with fenofibrate, a potent peroxisome proliferator. The most significant structure of the deduced protein is a modified peroxisomal targeting signal (Ser-Lys-Ile) at the carboxyl terminus that is regarded to be responsible for the unusual dual localization of the cytosolic epoxide hydrolase in peroxisomes as well as in the cytosol. In addition, a leucine zipper-like motif was identified at the amino terminus. Its possible implication for the observed dimeric structure of cytosolic epoxide hydrolase is discussed. The isolated cDNA was expressed in bacteria to yield a catalytically active enzyme. Specific activity of the crude lysate obtained exceeded that of rat liver cytosols from maximally induced animals by a factor of 8.

Amino Acid Sequence↗
PubMed1993

Functional organization of auditory cortex in the mongolian gerbil (Meriones unguiculatus). I. Electrophysiological mapping of frequency representation and distinction of fields.

The frequency representation within the auditory cortex of the anaesthetized Mongolian gerbil (Meriones unguiculatus) was studied using standard microelectrode (essentially multiunit) mapping techniques. A large tonotopically organized primary auditory field (AI) was identified. High best frequencies (BFs) were represented rostrally and low BFs caudally along roughly dorsoventrally oriented isofrequency contours. Additional tonotopic representations were found adjacent to AI. Rostral to AI was a smaller field with a complete tonotopic gradient reversed with respect to that in AI (mirror image representation) and was termed the anterior auditory field (AAF). BFs in the range from 0.1 to 43 kHz, apparently covering the hearing range of the Mongolian gerbil, were found in AI and AAF. Units in these two core fields responded to narrow frequency ranges with short latencies. Ventral to the common high-frequency border to AAF and AI, a rapid transition to very low BFs suggested the presence of a ventral field (V). Caudal to AI two small tonotopically organized fields were identified, a dorsoposterior field (DP) and a ventroposterior field (VP). The VP showed a tonotopic organization mirror imaged to that of AI, i.e. low frequencies were represented rostrally near the caudal border of AI, and high frequencies caudally. The DP showed a concentric frequency organization with high BFs located in the centre. Units in DP and VP fired less strongly, with considerably longer latencies, and responded to a broader range of frequencies than units in AI and AAF. Dorsocaudal to AI a dorsal field (D) was identified, harbouring units that responded to very broad ranges of frequencies. A tonotopic organization of field D could not be discerned. In the border region of AI and D, low-frequency responses were similar to those found in parts of AI and AAF, but without a clear-cut tonotopic organization. This region was termed Ald. The two core fields AI and AAF appeared to be located within the koniocortex, while the remaining fields lay outside. Our data show that the organization of the gerbil auditory cortex is highly elaborate, with parcellation into fields as complex as in cat or primates.

Acoustic Stimulation↗
PubMed1993

Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes.

The influence of cell-substrata interactions on the preservation of basal or in-vivo-induced microsomal cytochrome P-450 isoenzyme contents in cultured rat hepatocytes and on the adaptive responses after exposure to phenobarbital or 3-methylcholanthrene in vitro, was investigated. Hepatocytes from untreated or phenobarbital-treated rats were cultured in serum-free, aprotinin-supplemented culture medium in 96-well microtiter plates coated with collagen type I (COL), laminin, fibronectin or crude liver membrane fractions/collagen type I (CMF/COL). Basal cell functions were characterized by measuring the total protein content and lactate dehydrogenase release. The relative contributions of CYP1A1/2, CYP2B1/2, CYP2C6, CYP2C11, CYP3A and CYP4A isoenzymes were determined with ELISA using monoclonal antibodies raised against purified cytochromes P-450 from rat liver microsomes. The characterization of the CMF revealed that contaminations with mitochondria, nuclei and lysosomes are relatively low. Among these, membranes derived from the endoplasmic reticulum appeared to be the major organelle contaminant of the CMF. The matrix components laminin, fibronectin and collagen type IV were found in appreciable amounts. Hepatocytes from untreated rats, cultured for up to nine days on CMF/COL-coated plates, retained their relative cytochrome P-450 contents at 1.5-3-fold higher levels when compared to cells cultured on COL, fibronectin or laminin. Similarly, hepatocytes from phenobarbital-treated rats preserved the contents of barbiturate-inducible CYP2B1/2 and CYP3A proteins best when cultured on CMF/COL. After exposure of hepatocytes cultured on CMF/COL to phenobarbital from days 3-6, CYP3A proteins were enhanced more than twofold and CYP2B1/2, depending on the exposure level, increased 1.3-6-fold. After exposure to 3-methylcholanthrene, a threefold increase of CYP1A proteins was found in CMF/COL and laminin cultures. These results indicate that CMF/COL, as a substratum in rat hepatocyte cultures, regulates gene expression of cytochromes P-450 isoenzymes for up to 9 days and provides a matrix which enables the cells to respond qualitatively similar to the response observed in different zones of the liver. This activity cannot be replaced by single-matrix components.

Animals↗