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Biomedical subjects

M J Thomas

Publications and source records attributed to M J Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Superoxide generation by the human polymorphonuclear leukocyte in response to latex beads.

In this study, superoxide formation was not immediately detected when polymorphonuclear leukocytes were treated with linoleyl alcohol-coated, carboxy-modified latex beads. However, all other measures of neutrophil activation were present. Superoxide was not detected until 30 min after the initial exposure to beads. However, an O2(-)-producing, NADPH-dependent oxidase is active 15 min after exposure. When polymorphonuclear leukocytes are pretreated with cytochalasin B, superoxide production is detected immediately after exposure to the beads. Superoxide secretion after treatment with linoleyl alcohol-coated latex beads is compared with the response to other latex beads. The results imply that neutrophils form a phagolysosome around linoleyl alcohol-coated latex beads that is tightly sealed and does not allow superoxide to escape into the medium where it could be detected by the reduction of ferricytochrome c.

Cells, Cultured↗
PubMed1992

Urate causes the human polymorphonuclear leukocyte to secrete superoxide.

The human polymorphonuclear leukocyte generates O2-. and H2O2 when it is treated with uric acid. A transition metal catalyzed reaction between O2-. and H2O2 can give the hydroxyl radical and myeloperoxidase forms hypochlorous acid from H2O2 and chloride. Therefore, the uric acid-induced secretion of oxidants may be responsible for a large part of the inflammation associated with gout.

Free Radicals↗
PubMed1992

Renal oncocytoma and granular renal cell carcinoma. A comparative clinicopathologic and DNA flow cytometric study.

Twenty-three renal oncocytomas and 18 granular renal cell carcinomas (GRCC) were comparatively studied clinicopathologically and by DNA flow cytometry to delineate their differences. Of the patients with renal oncocytomas, 15 were men and 8 were women, and their ages ranged from 42 to 81 years (mean, 64 years). The gross appearance of renal oncocytomas was characteristically homogeneous tan-brown, with variable scarring, without areas of large hemorrhage, and with no apparent necrosis. Twenty-two renal oncocytomas were confined within the kidney (Robson stage I) and one tumor extended into the renal vein (stage IIIa). Twenty-two renal oncocytomas, including the stage IIIa tumor, manifested diploid DNA content and only one neoplasm showed a feature suggestive of near-diploid DNA aneuploidy. Of the 17 patients with renal oncocytomas who had adequate follow-up, none developed metastasis or died of disease. Of the patients with GRCC, 13 were men and 5 were women, and their ages ranged from 30 to 73 years (mean, 53 years). The gross appearance of GRCC was variegated, yellow to tan, and punctuated with geographic areas of necrosis. Eleven patients with GRCC were stage I, 4 were stage II, 2 were stage IIIa, and 1 patient had metastases at initial examination (stage IV). Seven GRCCs were DNA diploid, one was DNA tetraploid, and 10 tumors were DNA aneuploid. Twelve patients were alive with no evidence of disease (12 to 36 months; median, 26 months). All patients with DNA diploid neoplasm pursued benign clinical courses. One patient was alive with metastatic disease and two patients developed metastases and died of their disease; all three patients had DNA aneuploid tumors. Two patients died of other causes and one patient was lost to follow-up. Our data indicate that renal oncocytoma is a distinct clinicopathologic disease with characteristic gross, histologic, DNA flow cytometric, and biologic features that are different from GRCC.

Adenoma↗
PubMed1992

Cost-effectiveness of a back school intervention for municipal employees.

This study investigated the effect of a back school rehabilitation program on lost work time, lost time cost, medical cost, and number of injuries in municipal employees. Seventy back-injured workers who participated in a 6-week back school were compared on the dependent variables with 70 randomly selected back-injured city employees who had not participated in a back school. Back school participants demonstrated a significant decrease on all dependent variables. Back school participants had significantly fewer injuries in the 6-month postintervention period. No statistically significant differences were found between groups on the time and cost variables. Actual dollars saved in lost time and medical costs between groups was of practical value to the city. Study findings offer support for the back school as a cost-effective measure.

Absenteeism↗
PubMed1992

Characterization of the Streptococcus adjacens group antigen structure.

Serological classification of bacteria requires the presence of an antigen unique to the organism of interest. Streptococci are serologically differentiated by group antigens, many of which are carbohydrates, although some are amphiphiles. This report describes the chemical characterization of the Streptococcus adjacens group antigen structure. Previous studies demonstrated that the amphiphile contained phosphorus, ribitol, galactose, galactosamine, alanine, and fatty acids. Phosphodiester bonds present in the purified group antigen were identified as part of a poly(ribitol phosphate), since ribitol phosphate was the only organic phosphate detected after acid hydrolysis. Hydrofluoric acid cleavage of the phosphodiester bonds generated oligosaccharide repeating units. Gas chromatography-mass spectrometric analysis of the methylated, acetylated oligosaccharide suggested that the repeating unit is a trisaccharide of Galp beta 1-3Galp beta 1-4GalNac with N-acetylgalactosamine attached in beta-linkage to either the number two or the number four carbon of ribitol. The lipid- and carbohydrate-substituted poly(ribitol phosphate) of the S. adjacens group antigen therefore is a unique amphiphile structure, differing in its repeating-unit structure from the polyglycerophosphate structure of the more common gram-positive amphiphile lipoteichoic acid.

Alanine↗
PubMed1992

Evaluation of a novel calcium channel blocker, (S)-emopamil, on regional cerebral edema and neurobehavioral function after experimental brain injury.

The authors investigated the effects of a novel calcium channel blocker, (S)-emopamil, on cerebral edema and neurobehavioral and memory function following experimental fluid-percussion brain injury in the rat. Two independent experiments were performed to evaluate the effects of this compound on cardiovascular variables and postinjury cerebral edema (increases in tissue water content), and on cognitive deficits and neurological motor function following brain injury. Treatment with (S)-emopamil significantly reduced focal brain edema at 48 hours after brain injury. Profound memory dysfunction induced by brain injury was significantly attenuated following (S)-emopamil treatment. In addition, (S)-emopamil also attenuated the deficits in motor function that were observed over a 2-week period following brain injury. These results suggest that changes in calcium homeostasis may play an important role in the pathogenesis of trauma to the central nervous system and that the calcium channel blocker (S)-emopamil might be a useful compound for the treatment of traumatic brain injury.

Animals↗
PubMed1992

[First observations on the main plasma parameters of oxidative stress in homozygous sickle cell disease].

The present study report 7 cases of sickle homozygous disease which have been analysed using markers of the oxidative-stress, 26 african male subjects were studied: 7 Hb SS subjects (age: m = 20) and 19 control subjects (Hb AA, age: m = 40). Plasma concentrations of F-MDA, T-MDA, TBARS, alpha tocopherol, retinol and beta carotene were measured. Plasma MDA and TBARS mean levels increased in sickle homozygous patients more than in controls. However, only TBARS mean concentrations were significantly increased between patients and controls: TBARS: 4.14 +/- 1.49 nMol/ml for Hb SS versus 2.10 +/- 1.21 nMol/ml for Hb AA (P less than 0.005). Vitamin A and vitamin E concentrations were significantly lower in Hb SS than in Hb AA. Beta carotene was significantly increased in patients vs controls. The significant increase of TBARS explains the great importance of the oxidative damage, whereas the significant decrease of vitamins A and E, may contribute, at least for a part, to maintain the autoxidation process or reveals its intensity in these patients.

Adolescent↗
PubMed1992

Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus.

Despite intensive study, the neurobiological basis of epilepsy and persistent memory impairment following traumatic head injury remains unknown. Since abnormalities of the hippocampus are known to be associated with temporal lobe seizures and memory dysfunction, we investigated the effects of experimental traumatic brain injury on hippocampal structure and function in the rat. Using a model of fluid-percussion injury, we have discovered that neurons of the dentate hilus are vulnerable to a brief, unilateral impact to the extradural surface of the brain. One week after trauma, there was a dramatic reduction in hilar neurons ipsilateral to the impact, and a milder but significant decrease in neurons on the contralateral side as well. This neuronal loss was highly selective since adjacent dentate granule and pyramidal neurons appeared relatively unaffected. Immunocytochemistry showed that the hilar cell loss included a loss of somatostatin-immunoreactive neurons, and degeneration stains provided evidence that irreversible hilar injury occurred within 4 hr of impact. To assess the functional effects of the hilar damage, dentate granule cell field potentials were measured in response to perforant path stimulation. This revealed abnormal dentate granule cell hyperexcitability at 2.0 Hz stimulation in many of the injured animals. The presence of abnormal hyperexcitability correlated with the loss of hilar neurons. Thus, a momentary impact to the surface of the brain can cause selective, bilateral hippocampal injury with associated abnormalities in dentate gyrus physiology. Furthermore, the pattern of cell loss is similar to that observed in some patients with temporal lobe epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tissue clay: an experimental model to evaluate its performance in soft tissue augmentation and its biologic fate.

Tissue clay (a mixture of autologous whole blood and microfibrillar collagen--Avitene) has been proposed as a medium for reconstruction in cosmetic and reconstructive deformities of the face. Its performance and biologic fate has not been evaluated experimentally. The current study employs a model using the rabbit pinna to determine, histologically, the fate of a tissue clay implant.

Animals↗
PubMed1991

Synovial sarcoma. Inter-relationship of the biphasic and monophasic subtypes.

In order to assess minimum diagnostic criteria for synovial sarcoma, particularly the monophasic variety, and the inter-relationship between the monophasic and biphasic types, 32 examples were studied histologically, immunohistochemically (26 cases), and ultrastructurally (13 cases). Of the six biphasic synovial sarcomas examined by electron microscopy, the spindle cell component did not show evidence of epithelial differentiation or resemble the epithelial phase, but did appear fibroblastic; no tumor cells transitional between the spindle and epithelial component were evident. In contrast, all of the seven monophasic lesions had ultrastructural growth patterns and some cellular features approximating the epithelial cells of the biphasic variant. In 11 biphasic synovial sarcomas, epithelial membrane antigen was detected in the glandular epithelium of all cases and cytokeratins in eight cases; in no case were these antigens detected in the spindle cell regions of biphasic lesions. Of the 15 monophasic synovial sarcomas, two were positive for cytokeratins and four for epithelial membrane antigen. Thus, the detection of epithelial markers either immunohistochemically or by electron microscopy (or both) should be the minimal diagnostic criteria for monophasic synovial sarcomas. Based on these findings, it is suggested that monophasic synovial sarcomas do not represent the spindle cell or "stromal" phase of biphasic synovial sarcomas, but are a poorly differentiated variant of the latter. As others have suggested, these tumors are, in fact, carcinosarcomas and carcinomas of the soft tissues and the designation synovial sarcoma is inappropriate for this tumor class.

Adolescent↗
PubMed1991

Evaluation of memory dysfunction following experimental brain injury using the Morris water maze.

Memory dysfunction, a common clinical feature of traumatic brain injury (TBI), is thought to be related to secondary damage of key anatomic structures in the brain, including the hippocampus. In the present study, we have characterized and evaluated a novel experimental paradigm using the Morris water maze (MWM) technique, to measure post-TBI memory retention after lateral (parasagittal) fluid percussion (FP) brain injury in rats. Male Sprague-Dawley rats (n = 37) received a total of 20 training trials over 2 days in the MWM. Two and a half hours after the last training trial, the animals received FP brain injury of moderate severity (2.3 atmospheres, n = 12), high severity (2.6 atm, n = 13), or no injury (n = 12). Forty-two hours after FP brain injury, we observed a highly sufficient memory dysfunction in animals from both injury groups compared to the uninjured group (p less than 0.001). The degree of memory dysfunction was found to be directly related to the severity of injury, with the high severity group scoring significantly worse than the moderately injured group (p = 0.15). In addition, hippocampal cell loss was observed after brain injury, but only unilaterally. These data suggest that lateral FP brain injury causes memory dysfunction possibly related to concurrent hippocampal cell loss and that posttraumatic memory deficits may be sensitively quantitated using the memory testing paradigm described.

Animals↗
PubMed1991

The use of water-soluble radical scavengers to detect hydroxyl radical formation by polymorphonuclear leukocytes.

The polymorphonuclear leukocyte secretes both O2- and H2O2 when stimulated by various soluble or particulate stimuli. Since a reaction involving iron, O2-, and H2O2 could generate the hydroxyl radical (HO.) there has been speculation that the HO. may participate in the bactericidal activity of the neutrophil. A variety of water-soluble HO. scavengers have been used to test for the participation of HO. and the results imply that HO. might participate. However, other workers have not been able to detect the formation of significant amounts of HO. by the activated neutrophil. We have examined the effect of several commonly used HO. radical scavengers on the ability of the neutrophil to secrete O2- and H2O2. Several of these compounds actively inhibit secretion without affecting the viability of the neutrophil. After considering the various complications inherent in using water soluble radical scavengers, we suggest that they only be used with well defined experimental systems.

Allopurinol↗
PubMed1991

Hydrogen peroxide modification of human oxyhemoglobin.

The effect of H2O2 on the primary structure of OxyHb was studied. Upon treatment of OxyHb with H2O2 ([Heme]/[H2O2] = 1), tryptophan and methionine residues of the beta-chain were modified. Treatment of ApoHb with H2O2 resulted in the modification of histidine and methionine residues in both globin chains. Tryptophan residues were unaffected. Modification of methionine residues in both the beta-chain of OxyHb and ApoHb probably results from the direct oxidation of methionine by H2O2. The modification of histidine residues in ApoHb may be mediated by a metal-catalyzed oxidation system comprised of H2O2 and histidine-bound iron. The H2O2-mediated modification of tryptophan in the OxyHb beta-chain, however, requires the heme moiety.

Amino Acids↗
PubMed1990

A new bifunctional spin-label suitable for saturation-transfer EPR studies of protein rotational motion.

A new bifunctional spin-label (BSL) has been synthesized that can be immobilized on the surface of proteins, allowing measurement of rotational motion of proteins by saturation-transfer electron paramagnetic resonance (STEPR). The spin-label contains a photoactivatable azido moiety, a cleavable disulfide, and a nitroxide spin with restricted mobility relative to the rest of the label. The label reacts with surface lysine residues modified with beta-mercaptopropionate. Bifunctional attachment is achieved by photoactivation of the azido group. Any spin-label that remains monofunctionally attached after photolysis is removed by reduction of the disulfide. Only bifunctionally attached BSL remains on the protein. Hemoglobin was used to test the utility of the BSL in STEPR by comparison with hemoglobin modified with maleimide spin-label (MSL), a commonly used standard for the STEPR technique. MSL is a monofunctional spin-label which is fortuitously immobilized by local protein structure within hemoglobin. The BSL labeling of hemoglobin did not significantly affect the quaternary structure of hemoglobin as determined by gel filtration chromatography. The conventional EPR spectra of the mono- and bifunctionally attached BSL-hemoglobin were similar to the MSL-hemoglobin spectrum, indicating that both forms of BSL were rigidly bound to hemoglobin. In contrast, the spectrum obtained by reaction of modified hemoglobin lysine residues with MSL indicated that these labels were highly mobile. The monofunctionally attached BSL was mobilized upon octyl glucoside addition whereas bifunctionally attached BSL was only slightly mobilized, suggesting that hydrophobic interactions immobilize the monofunctionally attached label on hemoglobin. The response of STEPR spectra of mono- and bifunctionally attached BSL-hemoglobin to changes in hemoglobin rotational correlation time was similar to the MSL-hemoglobin over the range of 10(-5)-10(-3) s. The spectra of bifunctionally attached BSL indicated slightly less motion than corresponding spectra for MSL or monofunctionally attached BSL. The new BSL is a good reporter of protein rotation and does not require unique protein structures for its immobilization on the protein. Thus, the BSL should be more generally applicable for STEPR studies of membrane protein rotation than existing monofunctional spin-labels.

Cross-Linking Reagents↗
PubMed1990

Z-DNA formation in the rat growth hormone gene promoter region.

The complete DNA sequence of the 1.7 kilobase pairs (kbp) 5' of the rat growth hormone gene (rGH) has been determined and analyzed for Z-DNA-forming potential. Regions of alternating purine-pyrimidine (APP) sequences located between -1047 and -986 [(GT)31], between -445 and -433 bp, and between -426 and -403 bp relative to the rGH RNA transcription initiation site were identified and shown to form Z-DNA in negatively supercoiled plasmids by two-dimensional gel electrophoresis. Free-energy calculations indicated that Z-DNA forms most readily in the proximal Z-DNA regions. Diethyl pyrocarbonate footprinting of physiologically supercoiled plasmid DNA confirmed the presence of Z-DNA from -444 to -404 bp spanning the two most proximal APP sequences and a short non-APP sequence in between. DNA sequence analysis also predicted a region of DNA curvature near this proximal Z-DNA region. Formation of Z-DNA in the distal Z-DNA region consisting of a (GT)31 repeat was constrained at physiological plasmid superhelical densities. This may be related to the presence of DNA sequences (-1584 to -1559) 512 bp upstream of (GT)31 that undergo cruciform formation and thereby utilize the available free energy. Removal of 580 bp containing the cruciform region resulted in Z-DNA formation within (GT)31, thus demonstrating that deletion mutations can exert topological changes at a distance within the rGH 5'-flanking region. Methylation of two specific cytosines in the rGH 5'-flanking DNA that have been associated with inhibition of rGH promoter activity had no effect on Z-DNA formation. No evidence for DNA secondary structure formation within the rGH second exon-intron or 3'-flanking region was observed. We conclude that the rGH 5'-flanking region undergoes secondary-structure formation at physiological superhelical densities, thus providing a potential mechanism(s) for modulating rGH activity.

Alkylation↗
PubMed1990

Ca2+ transport in myocardial sarcolemma from rainbow trout.

Sacrolemmal vesicles were isolated from trout ventricles with a yield of 0.51 mg protein/g wet wt of a fraction enriched approximately 15-fold over the crude homogenate as estimated by K(+)-stimulated p-nitrophenylphosphatase (K(+)-pNPPase) activity. Although the K(+)-pNPPase specific activity compared favorably with that of the rat heart, there were some striking differences in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis and specific phospholipid content (mumol/mg protein) of the sacrolemmal fractions between the two species. Two major sarcolemmal Ca2(+)-transport proteins were investigated, the Na(+)-Ca2+ exchanger and the dihydropyridine (DHP) receptor, a component of the voltage-dependent L-type Ca2+ channel. From the initial rates of Na(+)-dependent Ca2+ uptake, it was determined that the exchanger has an apparent Km for Ca2+ of 14 +/- 1 microM and a maximum velocity of 7.7 +/- 1.1 nmol.mg protein-1.s-1 at 21 degrees C. Experiments using the DHP ligand [3H] (+) PN 200-110 to characterize the equilibrium binding to the DHP receptor in the sarcolemmal fraction yielded a Kd of 0.08 nM and maximum binding sites of 3.06 +/- 0.49 pmol/mg protein. Given the smaller dimensions of the trout myocyte and the resultant higher sarcolemmal surface to cytosolic volume compared with the mammalian myocyte, these in vitro findings are consistent with the notion that Ca2+ transport across sarcolemma is a quantitatively important contributor of Ca2+ delivery to and removal from the contractile element.

Animals↗