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T W Seale

Publications and source records attributed to T W Seale.

At least 55 records · Page 3Linked to original sources
PubMed1985

Inheritance of amphetamine-induced thermoregulatory responses in inbred mice.

Two inbred strains of mice, DBA/2 and C57BL/6, differ in their responses to d-amphetamine-induced alteration of core temperature. At low doses of amphetamine (e.g., 2 mg/kg IP), both strains become markedly hypothermic within 10-20 minutes. High doses (e.g., 20 mg/kg IP) induce significant hyperthermia (+1.8 degrees C) in DBA/2 mice but have only a slight hyperthermic effect (+0.2-0.3 degrees C) effect on C57BL/6 mice. The phenotype of the F1 hybrid strain derived by crossing C57BL/6 by DBA/2 is indistinguishable from its C57BL/6 parent at a dose of 20 mg/kg IP, i.e., reduced responsiveness to amphetamine-induced hyperthermia is dominant. Analysis of the thermoregulatory responses of recombinant inbred derivatives (lines BXD-9, 11, 15, 19, 20, 21, 23, 27, 28, 30) suggest that the relative responses to amphetamine-induced hyperthermia is inherited in a simple Mendelian fashion. These results differ from other pairs of inbred mouse strains which have been compared. These findings identify yet another neuropharmacological difference between mouse strains C57BL/6 and DBA/2 and are reviewed in terms of neuroregulatory mechanisms effecting thermoregulation.

Amphetamine↗
PubMed1985

A single gene difference determines relative susceptibility to caffeine-induced lethality in SWR and CBA inbred mice.

Inbred mouse strains SWR and CBA differ markedly in their relatively susceptibility to the acute toxic effects of intraperitoneally administered caffeine. At a dose of 187 mg/kg, SWR mice survive a stress-potentiated lethality test apparently related to the generation of tonic seizures; in contrast, CBA mice usually die in less than 30 seconds after this dose. Progeny from several different genetic crosses were characterized to determine the genetic basis underlying this phenotypic difference in caffeine sensitivity. F1 progeny from reciprocal crosses of the parental strains were uniformly sensitive to caffeine-induced lethality, i.e., caffeine responsiveness behaves like an autosomal dominant trait. Self-crossing of F1 individuals produced both progeny which were resistant to caffeine-induced lethality (26% of the total) and those which were susceptible (74%). Backcrosses of the F1 animals to the CBA parent produced no (0/19) resistant progeny. In contrast, backcrosses of F1 animals to SWR produced 54% resistant progeny. These data indicate that the difference in susceptibility to caffeine-induced lethality between these strains is determined by a single pair of autosomal alleles in which susceptibility (responsiveness) to this methylxanthine is dominant to resistance (nonresponsiveness).

Animals↗
PubMed1984

Plasma and submandibular saliva lysosomal enzymes in cystic fibrosis.

This study determined in a blind fashion the activity levels and thermostability properties of two lysosomal hydrolytic enzymes, acid phosphatase and alpha-mannosidase, in plasma samples from 25 cystic fibrosis (CF) patients and 25 age- and sex-matched normal controls. Mean alpha-mannosidase activity (3.2 +/- 1.0 mU/ml) and acid phosphatase activities (6.5 +/- 2.9 mU/ml) in CF patients were not significantly different from those found in normal individuals (2.8 +/- 0.7 and 7.6 +/- 3.4 mU/ml, respectively). Using stringent conditions no differences in thermostability properties of these enzymes were found between plasma from CF patients as compared to that of normal controls. When activity levels of these enzymes and of four additional hydrolytic enzymes, alpha-L-fucosidase, alpha-galactosidase, alpha-glucosidase and beta-galactosidase, were determined in submandibular saliva, no significant differences in enzyme levels between CF and age- and sex-matched controls were noted nor were thermostability differences found. Our data do not support the concept that altered properties of these enzymes are useful as markers for detection of CF homozygotes and heterozygotes, nor the hypothesis that the defect underlying this disease is a deficiency of post-translational modification of glycoproteins leading to their mis-compartmentalization and qualitative alteration.

Acid Phosphatase↗
PubMed1984

Systematic comparison of apomorphine-induced behavioral changes in two mouse strains with inherited differences in brain dopamine receptors.

Dosage and time dependencies of apomorphine-induced changes in stereotyped behaviors (climbing, gnawing and sniffing), locomotor activity and rearing activity were compared in young adult male mice of two inbred strains, DBA/2 and C57BL/6. These two strains are known to differ in their genetically specified brain dopamine receptor number. Apomorphine administered intraperitoneally at dosages of 0.5-20 mg/kg failed to induced stereotyped climbing in DBA/2 at any of the doses tested but markedly increased climbing in C57BL/6 at higher dosages. Apomorphine-induced stereotyped gnawing occurred in both strains at higher dosages although the latency was shorter and maximal effect greater in C57BL/6. Stereotyped sniffing was induced in both strains to a comparable degree at doses greater than or equal to 2.0 mg/kg, and the duration of this stereotypy was indistinguishable between strains. Locomotor activity was inhibited maximally in DBA/2 at an apomorphine dosage of 2 mg/kg and was inhibited to a greater extent than was C57BL/6. Rearing was inhibited in both strains by doses of apomorphine greater than or equal to 0.5 mg/kg; however the duration of the effect was considerably greater in DBA/2 than in C57BL/6. These data suggest that genetically determined differences in central dopamine receptors may have profound and selective effects on behaviors mediated by dopamine pathways; that complex behavioral patterns, e.g., apomorphine-induced stereotypy, may be dissected in to individual components by identifying neuropharmaco genetic differences between strains; that marked strain-specific, inherited differences in dopamine agonist-induced behavioral changes do occur among inbred, non-mutant mouse strains and that their occurrence in other mammalian species including man should be considered.

Animals↗
PubMed1984

Interstrain variation in acute toxic response to caffeine among inbred mice.

Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, SWR/J). C57BL/6J, chosen as a "prototypic" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals.

Animals↗
PubMed1983

Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase.

Decreased glucocorticoid binding has been observed at a time after endotoxin (3 to 6 h) when imparied liver enzyme induction is known to occur. This study was undertaken to characterize the early time course of hypoglycemia and decreased liver phosphoenolpyruvate carboxykinase (PEPCK) activity in intact and adrenalectomized mice given endotoxin. In addition, altered steroid induction of hepatic PEPCK was examined in adrenalectomized mice given dexamethasone at intervals before and after a median lethal dose of endotoxin. Intact mice demonstrated a dramatic hyperglycemia at 1 h after endotoxin treatment, a response absent in adrenalectomized mice. Plasma glucose levels were significantly reduced from control values at 3 and 6 h posttreatment, with the most pronounced endotoxin-induced hypoglycemia seen in adrenalectomized mice. Hepatic PEPCK activity in intact mice given endotoxin was decreased at 3 and 6 h after treatment, although no change from basal, noninduced levels was seen in poisoned adrenalectomized mice. The increased increment in hepatic PEPCK activity due to fasting of intact control mice was reproduced in adrenalectomized control mice by the administration of dexamethasone. Furthermore, the induction of hepatic PEPCK by dexamethasone was inhibited by 1 h after endotoxin treatment, with enzyme activity falling to basal, noninduced levels by 6 h posttreatment. At these same time intervals after endotoxin treatment, no evidence of histopathology in the liver or adrenal glands was seen. These results coincide with changes in steroid binding seen previously and indicate that endotoxin treatment produces significant alterations in glucocorticoid action at the subcellular or molecular level.

Adrenal Glands↗
PubMed1982

Increased cerebrospinal fluid free amino acid concentrations in children with bacterial meningitis.

19 free amino acids were measured by Durrum high pressure chromatography in the cerebrospinal fluid of 19 children, 9 with and 10 without bacterial meningitis. Each of the amino acids, except for gamma-amino butyric acid, was significantly increased in meningitis. Values were elevated upon admission of these patients to the hospital, but the highest concentration for most of the amino acids was noted in specimens collected 24-48 h after initiation of antibiotic treatment. Upon the completion of successful antibiotic therapy, the amino acid concentrations returned to normal or near normal levels.

Amino Acids↗
PubMed1980

Cystic fibrosis factors: effect of serum on the secretory response of dispersed rat submandibular cells.

The action of serum from cystic fibrosis patients on the intracellular maintenance, efflux, and uptake of potassium ions in dispersed acinar cells from the rat submandibular gland, a seromucous salivary gland, was investigated in an attempt to demonstrate the presence of factors affecting ion-coupled secretion. No effects specific to cystic fibrosis serum were demonstrated upon the following parameters of potassium transport: (1) maximal stimulation of K+ efflux by the cholinergic agonists carbamylcholine; (2) the dose-response curve of K+ efflux in response to carbamylcholine; (3) re-entry of K+ into cells after carbamylcholine stimulation; (4) the maintenance of K+ in the absence of added effectors. No differences were observed between cells pretreated with serum and cells to which serum was added at the time of cholinergic stimulation of secretion. At high concentrations, serum from both normal individuals and those with cystic fibrosis severely damaged the cells in a rapid and irreversible fashion. K+ transport has a direct, closely coupled, specific relationship to secretory activity and is Ca++ dependent in this system. From these observations, we conclude that serum from individuals with cystic fibrosis does not contain chemical compounds which specifically alter the major components of ion-coupling to secretion or the secretory process itself in salivary gland acinar cells.

Adolescent↗
PubMed1979

Isolation and characterization of a polyamine-peptide conjugate from human amniotic fluid.

Significant amounts of the diamine putrescine and the polyamines spermidine and spermine could be detected in human third-trimester amniotic fluid only after acid hydrolysis. This observation was interpreted to mean that these amines existed only in conjugated form in this biological fluid. Upon fractionation by ultrafiltration 90--10% of the putrescine was associated with the 1000--10 000 dalton fraction. Spermine was identified in this fraction and in a low-molecular weight fraction presumably representing acetylated derivatives. Spermidine was entirely associated with the 10 000--30 000 dalton fraction. The putrescine conjugate was purified to homogeneity by column chromatography on Biogels P10 and P6 followed by ion-exchange chromatography on DEAE-Sephadex A-25. Molecular weight by gel exclusion using peptide standards was estimated to be approx. 4600. The UV absorption spectrum of the putrescine conjugate conformed to that expected for a polypeptide. This putrescine conjugate contained 39 identified amino acids with a combined molecular weight of 4713. Putrescine was detectable by high pressure liquid chromatography only after acid hydrolysis of the conjugate. No other polyamines were detected in these hydrolyzates, nor were any polyamines demonstable in hydrolyzates of control peptides nor in pooled column washes. The identity of the putrescine determined by high pressure liquid chromatography was confirmed by a two-dimensional thin-layer chromatography method. These results establish the in vivo production of a putrescine--polypeptide conjugate in man. Such molecular species may constitute yet another metabolic pathway for polyamines or may reflect another mode of post-translational modification of polypeptide structure and function. The qualitative and quantitative analysis of polyamine conjugate in human aminotic fluid may prove to be useful in the detection of abnormalities in fetal development.

Amino Acids↗
PubMed1979

Polyamine conjugates and total polyamine concentrations in human amniotic fluid.

A study of the quantitative profile of polyamines in amniotic fluid from the 13th through the 40th week of gestation was undertaken. These experimental observations indicate the absence of free putrescine, spermidine and spermine throughout gestation. Quantities of acid-liberated putrescine, spermidine and spermine are highest in late first and late third trimester. Putrescine is associated with peptide or peptides of molecular weight 1000 to 10 000 throughout gestation. Spermidine is found in amniotic fluid covalently conjugated to peptide or peptides with molecular weight 10 000 to 30 000. Spermine appears to exist in amniotic fluid, both in the higher molecular weight fraction (1000 to 10 000) and as acetylated derivatives. The existance of polyamine conjugates is compatible with an in vivo function in the regulation of embryonic growth and development. Abnormalities in polymines conjugated to peptides or their concentration may be useful in the diagnosis of fetal maldevelopment.

Amniotic Fluid↗
PubMed1979

Scanning electron microscopy of surface ultrastructure changes during meiosporangium maturation and meiospore liberation in the aquatic fungus Allomycpes arbuscula.

Alterations in wall ultrastructure accompanying resistant sporangium maturation and meiospore liberation in Allomyces arbuscula were examined by scanning electron microscopy. Three discrete wall layers were identified, each of which underwent marked changes during processes leading to zoospore release. The outermost wall layer, the hyphal sheath continuous with the hypha, was physically altered during the maturation process preparatory to induction and release of meiospores. The integrity of this wall layer was broken, and it was no longer closely juxtaposed to the heavy pitted wall layer that lay beneath it. A fibrillar matrix seemed to cement the two layers to one another before this desiccation. A single, raised, longitudinal dehiscence ridge on each meiosporangium appeared to be a structurally differentiated region of the pitted wall layer at which sporangium rupture occurred to permit emergence of the protoplast. By its thickness the pitted wall layer was likely to provide mechanical rigidity to the meiosporangium. Beneath the pitted wall layer, another thin, flexible wall layer surrounded the protoplast. From this structure, a single exit papilla was cleaved at the apical region to effect the release of meiospores from the protruding protoplast. Thus a sequence of structural changes in well-differentiated multiple wall layers is implicated in the sporulation process in this organism.

Cell Wall↗
PubMed1979

Serotypes and antibiotic susceptibilities of Pseudomonas aeruginosa isolates from single sputa of cystic fibrosis patients.

A phenotypic characterization of Pseudomonas aeruginosa from single sputum samples of 21 typical cystic fibrosis patients indicated a high frequency of heterogeneity among isolates on the basis of differences in antibiotic resistance, colony morphology, pigmentation, and serotype. Two or more isolates with different but stable susceptibilities to carbenicillin, gentamycin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole plus trimethoprim were detected in 38% of the sputa. Differences generally were independent of the mucoid state of the strain. O-antigen group determination with the Difco typing set showed that two or more serologically distinct strains were present in 10/21 sputum specimens. Nonmucoid derivatives of mucoid isolates almost always retained both the antibiotic susceptibilities and serotype of their parent strain. These data suggest that cystic fibrosis patients may be cocolonized/coinfected by different strains of P. aeruginosa more frequently than generally believed. Alternatively, phenotypically distinct strains from a single patient might arise as phenotypic dissociants from a single infecting strain. Because of the frequency and multiplicity of phenotypically distinct P. aeruginosa isolates which we obtained from our cystic fibrosis patients, it is important to select multiple isolates from sputum cultures for antimicrobial susceptibility testing so as to assess adequately the susceptibility of this organism to antibiotic therapy in cystic fibrosis. We recommend that several colonies of each distinguishable colony type of P. aeruginosa be pooled for the antibiogram.

Adolescent↗
PubMed1977

Amino acid replacements resulting from suppression and missense reversion of a chain-terminator mutation in Neurospora.

The Neurospora crassa super-suppressor mutation, ssu-1, suppresses the auxotrophic phenotype of the mutant am(17) by inserting tyrosine at residue 313 of NADP-specific glutamate dehydrogenase, a position occupied in the wild type by glutamate. Two classes of am(17) revertants due to further mutation within the am gene have, respectively, tyrosine and leucine at residue 313. These replacements are consistent with a chain-terminating codon in am(17) of either the amber (UAG) or the ochre type (UAA), but are inconsistent with UGA. The Leu313 and Tyr313 variants of the enzyme have effective activity but are grossly different from the wild type in Michaelis constants (especially for ammonium) and heat stabilities at two different pH values. They show smaller but significant differences in these respects from each other.

Amino Acid Sequence↗
PubMed1976

Super suppressor action spectrum in Neurospora.

The action of super suppressors mapping at eight separate loci upon ten different nonsense mutants is examined. These suppressors can be subdivided into seven classes based upon their capacity to restore function to the test mutants.

Chromosome Mapping↗
PubMed1975

Fruiting-body formation and myxospore differentiation and germination in Mxyococcus xanthus viewed by scanning electron microscopy.

Streaming cells, fruiting bodies, and single cells undergoing myxospore differentiation and germination were examined in the FB strain of Myxococcus xanthus by scanning electron microscopy. Myxospores differentiated in fruiting bodies differed in size, in kinetics of germination, in the fate of the myxospore capsule, and in the external structure of the walls of newly emerged cells when compared with myxospores differentiated in liquid medium after glycerol induction. Vegetative cells outgrowing from glycerol-induced myxospores were regularly pleomorphic, a condition that persisted through the first cell division.

Cell Aggregation↗