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Biomedical subjects

A Thom

Publications and source records attributed to A Thom.

At least 19 recordsLinked to original sources
PubMed2000

Comparison between one-session psychological treatment and benzodiazepine in dental phobia.

To compare the effects of a single session of psychological treatment and acute administration of benzodiazepine, 50 dental phobic patients were allocated either to psychological treatment, benzodiazepine, or no treatment for anxiety. Psychological treatment consisted of stress management training and imaginal exposure to phobic stimuli with homework assignments. Benzodiazepine was administered 30 min before dental treatment. Both treatment conditions led to less anxiety during dental surgery than did the control condition. Phobic patients in the benzodiazepine condition showed a relapse after dental treatment, whereas those in the psychological treatment condition showed further improvement until the follow-up 2 months later. Of the latter group, 70% continued dental treatment; only 20% and 10% returned in the benzodiazepine and control conditions, respectively.

Adult↗
PubMed1999

Stimulation of myofibrillar protein degradation and expression of mRNA encoding the ubiquitin-proteasome system in C(2)C(12) myotubes by dexamethasone: effect of the proteasome inhibitor MG-132.

Addition of the synthetic glucocorticoid, dexamethasone (Dex) to serum-deprived C(2)C(12) myotubes elicited time- and concentration-dependent changes in N(tau)-methylhistidine (3-MH), a marker of myofibrillar protein degradation. Within 24 h, 100 nM Dex significantly decreased the cell content of 3-MH and increased release into the medium. Both of these responses had increased in magnitude by 48 h and then declined toward basal values by 72 h. The increase in the release of 3-MH closely paralleled its loss from the cell protein. Furthermore, Dex also decreased the 3-MH:total cell protein ratio, suggesting that myofibrillar proteins were being preferentially degraded. Incubation of myotubes with the peptide aldehyde, MG-132, an inhibitor of proteolysis by the (ATP)-ubiquitin (Ub)-dependent proteasome, prevented both the basal release of 3-MH (>95%) and the increased release of 3-MH into the medium in response to Dex (>95%). Northern hybridization studies demonstrated that Dex also elicited similar time- and concentration-dependent increases in the expression of mRNA encoding two components (14 kDa E(2) Ub-conjugating enzyme and Ub) of the ATP-Ub-dependent pathway. The data demonstrate that Dex stimulates preferential hydrolysis of myofibrillar proteins in C(2)C(12) myotubes and suggests that the ATP-Ub-dependent pathway is involved in this response.

Adenosine Triphosphate↗
PubMed1999

Translocation of protein kinase C isoforms in rat muscle in response to fasting and refeeding.

Weanling rats were offered food ad libitum, or fasted for 18 h, or fasted and refed for times ranging from 5 to 30 min. Five protein kinase C (PKC) isoforms (alpha, epsilon, zeta, theta and mu) were detected in the hindlimb muscles by Western immunoblotting. PKC forms epsilon and theta were abundant in plantaris, but not in soleus muscle, and no difference in localization was detected between fed rats and those fasted for 18 h. PKC forms alpha and mu were affected by fasting and refeeding. PKC-mu was found only in the cytosolic fraction of the plantaris muscle of the fasted animal, but in the fully-fed animals it was also associated with the membrane fraction. The pattern of localization observed in the fully-fed state was restored in the fasted rats by 20 min refeeding. In contrast, PKC-alpha was not detected in the cytosolic fraction of the plantaris in fasted animals but rapidly reappeared there on refeeding, being restored to 20% and 80% of the fed value within 5 and 30 min of refeeding respectively. The timing of these changes was correlated with the increase in serum insulin concentration, which was significantly elevated above the fasted value by 5 min and at subsequent times. These data suggest a possible role for PKC isoforms alpha and mu in the metabolic changes that occur in skeletal muscle on transition between the fasted and the fed state.

Animals↗
PubMed1998

Growth and metabolism of fetal and maternal muscles of adolescent sheep on adequate or high feed intake: possible role of protein kinase C-alpha in fetal muscle growth.

From days 4-104 of pregnancy, adolescent sheep, weighing 43.7 (SE 0.87) kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76.5 (SE 4.5) v 50.0 (SE 1.7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (alpha, epsilon, theta, mu, zeta) were identified in fetal muscle. One of these, PKC-alpha was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in it subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Further parameters of insight and neuropsychological deficit in schizophrenia and other chronic mental disease.

Evidence has begun to accumulate which suggests that lack of awareness of illness in schizophrenia is related to and possibly the result of a cognitive deficit involving prefrontal cerebral dysfunction. This study further explores this relationship along with other domains of self-awareness in chronic schizophrenics and other subjects with serious mental disorders. One hundred eight schizophrenics and 21 bipolar subjects from three separate sites in Britain, Germany, and Canada were administered the Wisconsin Card Sorting Test and three measures of self-awareness. Lack of illness awareness and other domains of self-knowledge were significantly more related to poorer neuropsychological performance in schizophrenia patients than in the other subjects. The results support the hypothesis that lack of illness awareness is related to defective frontal lobe functioning as indexed by neuropsychological measures.

Activities of Daily Living↗
PubMed1997

Regulation of phospholipase D in L6 skeletal muscle myoblasts. Role of protein kinase c and relationship to protein synthesis.

The addition of vasopressin or 12-O-tetradecanoylphorbol-13-acetate (TPA) to prelabeled L6 myoblasts elicited increases in [14C]ethanolamine release, suggesting the activation of phospholipase D activity or activities. While the effects of both agonists on intracellular release were rapid and transient, when extracellular release of [14C]ethanolamine was measured, the effect of vasopressin was again rapid and transient, whereas that of TPA was delayed but sustained. Effects of both agonists on intra- and extracellular release were inhibited by the protein kinase C (PKC) inhibitor, Ro-31-8220, and PKC down-regulation by preincubation with TPA. The formation of phosphatidylbutanol elicited by vasopressin and TPA mirrored their effects on extracellular [14C]ethanolamine release in that the former was transient, whereas the latter was sustained. Responses to both agonists were abolished by PKC down-regulation. When protein synthesis was examined, the stimulation of translation by TPA and transcription by vasopressin were inhibited by Ro-31-8220. In contrast, down-regulation of PKC inhibited the synthesis response to TPA but not vasopressin. Furthermore, following down-regulation, the effect of vasopressin was still blocked by the PKC inhibitors, Ro-31-8220 and bisindolylmaleimide. Analysis of PKC isoforms in L6 cells showed the presence of alpha, epsilon, delta, mu, iota, and zeta. Down-regulation removed both cytosolic (alpha) and membrane-bound (epsilon and delta) isoforms. Thus, the elevation of phospholipase D activity or activities induced by both TPA and vasopressin and the stimulation of translation by TPA involves PKC-alpha, -epsilon, and/or -delta. In contrast, the increase in transcription elicited by vasopressin involves mu, iota, and/or zeta. Hence, although phospholipase D may be linked to increases in translation elicited by TPA, it is not involved in the stimulation of transcription by vasopressin.

Analysis of Variance↗
PubMed1997

Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells: effect of differentiation and fusion.

In proliferating C2C12 myoblasts, serum and physiological concentrations of insulin and IGF-I stimulated protein synthesis and RNA accretion. After fusion, the multinucleated myotubes remained responsive to serum but not to insulin or IGF-I, even though both insulin and type-I IGF receptor mRNAs increased in abundance. Protein synthetic responses to insulin and IGF-I in myoblasts were not inhibited by dexamethasone, ibuprofen or Ro-31-8220, thus phospholipase A2, cyclo-oxygenase and protein kinase C did not appear to be involved in the signalling mechanisms. Neither apparently were polyphosphoinositide-specific phospholipase C or phospholipase D since neither hormone increased inositol phosphate, phosphatidic acid, choline or phosphatidylbutanol production. Only the phosphatidylinositol-3-kinase inhibitor, wortmannin, and the 70 kDa S6-kinase inhibitor, rapamycin, wholly or partially blocked the effects of insulin and IGF-I on protein synthesis. 2-deoxyglucose uptake remained responsive to insulin and IGF-I after fusion and was also inhibited by wortmannin. The results suggest that the loss of responsiveness after fusion is not due to loss of receptors, but to the uncoupling of a post-receptor pathway, occurring after the divergence of the glucose transport and protein synthesis signalling systems, and that, if wortmannin acts at a single site, this is prior to that point of divergence.

Animals↗
PubMed1996

Cyclic AMP stimulates protein synthesis in L6 myoblasts and its effects are additive to those of insulin, vasopressin and 12-0-tetradecanoylphorbol-13-acetate. Possible involvement of mitogen activated protein kinase.

The role of cyclic AMP as a second messenger in the stimulation of protein synthesis and the potential involvement of mitogen activated protein (MAP) kinase in this response was studied in L6 myoblasts. Dibutyryl-cAMP (dbt-cAMP) increased protein synthesis at 90 min and 6 h in a concentration-dependent manner. The responses at 90 min were probably mediated by increased translation as they were not blocked by actinomycin D; effects at 6 h were accompanied by increases in RNA content implying a transcriptional component. 100 nM 12-0-tetradecanoylphorbol-13-acetate (TPA), 1 nM Insulin (90 min incubations) and 100 nM vasopressin (6 h incubation) also increased protein synthesis and these responses were additive with those of 500 micron dbt-cAMP. Responses to forskolin were similar to dbt-cAMP whilst 1,9-dideoxyforskolin had no effect. Cell extracts immunoblotted with MAP kinase antibody showed bands corresponding to approx. 42, 44, 54 and 83 kDa. 500 micron dbt-cAMP elicited an increase in activity of both the 42 and 44 kDa bands when assayed by the 'in gel' method and a similar response was also observed with forskolin. TPA and vasopressin also stimulated the activity of these two isoforms, but had no significant additive or inhibitory effects when added in combination with 500 micron dbt-cAMP. In contrast, although 1 nM insulin alone had no effect, a synergistic response in terms of MAP kinase activation was observed in the presence of dbt-cAMP. The data demonstrate that cAMP stimulates protein synthesis in L6 cells and suggest a role for MAP kinase in this event.

Animals↗
PubMed1996

Measurement of protein degradation by release of labelled 3-methylhistidine from skeletal muscle and non-muscle cells.

The rates of [3H]N(tau)-methylhistidine (3-MH) accumulation in the medium, following pulse labelling of cells for 48 h with [3H]methionine, were used to measure myofibrillar protein degradation. In fused C2C12 myotubes, incubation for 24 or 48 h after the labelling period gave rates of myofibrillar degradation of 38 and 42%/day. In a leucine free medium, these rates were similar; 40 and 47%/day, respectively. Using identical conditions +/- leucine, but in the absence of [3H]-methionine, rates of protein accretion and synthesis over 24-48 h were measured. From these data, rates of total protein degradation were calculated by difference and were similar to myofibrillar degradation rates. We have used the same pulse labelling protocol to assess whether the method is applicable to non-muscle cell lines based on the knowledge that 3T3 fibroblasts contain actin in the cytoskeleton. 3-MH was detected both in protein and upon its release into the medium. Actin degradation measured over a 48 h period gave a value half that obtained for total degradation, but the results suggest that the release of 3-MH by fibroblasts in vivo could be appreciable. The development of this methodology should provide a useful tool to investigate signalling mechanisms regulating actin degradation in a variety of cell types.

3T3 Cells↗
PubMed1996

N tau-methylhistidine turnover in skeletal muscle cells measured by GC-MS.

A method that employs gas chromatography-mass spectrometry has been developed to measure N tau-methylhistidine (3-methylhistidine; 3-MH) synthesis and release from skeletal muscle myotubes in vitro. It shows excellent linearity (0.9999) over the range studied (0-4 nmol), high recovery (92.6%), and low coefficient of variation (1.6%). 3-MH release from myotubes was essentially linear over a 96-h incubation, whereas the loss of 3-MH from cell protein accelerated with increasing time, an effect due, at lest in part, to decreasing rates of total protein synthesis. When incubated in either glutamine-free or methionine-free medium for 48 h, 3-MH in cell protein and appearing in the medium were greatly reduced compared with the 48-h controls, suggesting that hypertrophy was greatly reduced. Similar but lesser trends were observed with adenosine 3',5' -cyclic monophosphate. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) appeared to both stimulate 3-MII synthesis and inhibit its release during a 48-h incubation. The development of this method facilitates detailed investigation into the mechanisms through which agents such as TPA regulate myofibrillar protein degradation.

Bucladesine↗
PubMed1996

The Bargarran witchcraft trial--a psychiatric reassessment.

In 1697, seven people were condemned at Paisley for using witchcraft to torment Christian Shaw, daughter of the laird of Bargarran. For seven months, Christian had bizarre seizures during which she claimed to see the Devil and her tormentors assaulting her. She also exhibited pica and said that the foreign material had been forced into her mouth by her invisible assailants. The notable Glasgow physician, Matthew Brisbane, was consulted and gave evidence at the trial; he could find no natural explanation for the pica. It is likely that Christian had a dissociative (conversion) disorder after being cursed by a servant. Christian recovered and later married the minister of Kilmaurs. After his untimely death, she established a highly successful spinning business which lead to the Paisley cotton industry.

Dissociative Disorders↗
PubMed1996

Repartitioning of maternal muscle protein towards the foetus induced by a polyclonal antiserum to rat GH.

Growth and protein accretion were studied in maternal muscle and liver and in foetuses of rats on day 20 of pregnancy. In young rats, weighing 120 g at mating, muscle mass and protein content of three hind-limb muscles, soleus, plantaris and gastrocnemius, increased on average by 7% compared with non-pregnant controls although the rate of muscle protein synthesis was decreased. In mature rats, rates of muscle protein synthesis were also reduced on day 20 of pregnancy but no change in muscle mass was observed. Rates of liver protein synthesis and accretion were increased in the pregnant animals; the effect was larger in the young pregnant rat. Administration of an antibody to rat GH (anti-rGH) for 10 days to young pregnant rats reversed the effect on the same three maternal muscles and resulted in a 9-11% lower muscle mass and protein content, compared with control pregnant animals. In both young and mature dams serum IGF-I concentrations were halved on day 20 of pregnancy, a further small reduction was observed in response to anti-rGH. No significant change in serum insulin or corticosterone levels was observed. Anti-rGH treatment also reduced food intake but foetal weight at 20 days was significantly increased (14%). The effects on maternal muscle were not the result of loss of appetite associated with anti-GH administration as, in rats pair-fed to the intake of the anti-rGH group, maternal muscle and foetal weights were the same as in animals with food available ad libitum. The data suggest that the GH/IGF axis is involved in the partitioning of nutrients between the dam and the foetus.

Animals↗
PubMed1995

Evidence that protein kinase C and mitogen activated protein kinase are not involved in the mechanism by which insulin stimulates translation in L6 myoblasts.

Insulin stimulated a concentration-dependent increase in protein synthesis in L6 myoblasts which was significant at 1 nM. This response was not prevented by the transcription inhibitor, actinomycin D. The protein kinase C (PKC) inhibitor, Ro-31-8220, and downregulation of PKC by prolonged incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), had no effect on the ability of insulin to stimulate protein synthesis whilst completely blocking the response to TPA. In contrast, insulin failed to enhance protein synthesis significantly in the presence of either ibuprofen, a selective cyclooxygenase inhibitor or rapamycin, an inhibitor of the 70 kDa S6 kinase. When cell extracts were prepared and assayed for total myelin basic protein kinase activity, a stimulatory effect of insulin was not observed until the concentration approached 100-fold (i.e. 100 nM) that required to elicit increases in protein synthesis. Upon fractionation on a Mono-Q column, 100 nM insulin increased the activity of 3 peaks which phosphorylated myelin basic protein. Two of these peaks were identified as the 42 and 44 kDa forms of Mitogen Activated Protein (MAP) kinase by immunoblotting. In contrast, 1 nM insulin had no effect on the activity of these peaks. The data suggest that physiologically relevant concentrations of insulin do not stimulate translation in L6 cells through either PKC or the 42/44 kDa isoforms of MAP kinase and that this response is, at least in part, mediated through the activation of the 70 kDa S6 kinase by cyclooxygenase metabolites.

Amino Acid Sequence↗
PubMed1995

Sialylation of intestinal microvillar membranes in newborn, sucking and weaned pigs.

Affinity cytochemistry and biochemistry revealed distinctive temporal changes in the expression of sialylated and compositionally related membrane glycoconjugates in the pig small intestine between birth and weaning. The expression of membrane NeuAc alpha 2,6 moieties, recognized by Sambucus nigra agglutinin-1, was high in newborn pigs, declined slightly during sucking and was very low in weaned animals. Conversely, the expression of membrane NeuAc alpha 2.3 moieties, recognized by Maackia amurensis agglutinin-2, was low at birth but higher in sucking and weaned animals. Histoblood group O- and A-antigen expression was first detected in a minority of sucking pigs, but was evident in all weaned pigs examined. Lactase glycoforms were isolated from solubilized microvillar membranes of newborn and weaned pigs. The newborn (predominantly alpha 2,6-sialylated) and weaned (predominantly alpha 1,2-fucosylated) glycoforms exhibited similar specific activity, indicating that postnatal lactase decline in the pig intestine is unrelated to temporal changes in membrane sialylation and fucosylation.

Agglutinins↗
PubMed1995

[Diagnosis using nuclear medicine of anterior descending artery stenosis in patients with left bundle branch block].

PURPOSE: To evaluate septal perfusion and contractility in patients with left bundle branch block (LBBB). METHODS: Twenty patients were submitted to myocardial scintigraphy with Tecnecium-99m isontrile after exercise and dipyridamole infusion. The septal contractility was observed during the radionuclide ventriculography. All patients were submitted to coronariography. RESULTS: Twenty patients were studied and 17 (85%) had a normal left anterior descending (LAD) artery. Nine (53%) patients had abnormalities in septal perfusion after the exercise and 2 (12%) after dipyridamole infusion. All patients had abnormalities in septal contractility during the radionuclide ventriculography. CONCLUSION: The myocardial scintigraphy after dipyridamole infusion showed better specificity in the diagnosis of a LAD lesion. The radionuclide ventriculography was an efficient method to evaluate the septal contraction abnormalities in patients with LBBB.

Bundle-Branch Block↗
PubMed1994

Stimulation of protein synthesis and phospholipase D activity by vasopressin and phorbol ester in L6 myoblasts.

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and vasopressin on protein synthesis and phospholipase D (PLD) activity were investigated in L6 myoblasts. TPA stimulated a concentration-dependent increase in protein synthesis (EC50 approx. 10 nM) during a 90 min incubation, but had no effect after 6 h. The maximum increase was about 15% and was mediated through changes in translation, as TPA had no effect on RNA accretion and the response was not prevented by actinomycin D. TPA also stimulated PLD activity as measured by an 8-fold increase in the formation of phosphatidylbutanol (PtdBuOH) and the release of choline (EC50 5-10 nM). In contrast to TPA, vasopressin stimulated protein synthesis (maximum increase 30%, EC50 approx. 10 nM) and RNA accretion after 6 h, but had no effect after 90 min. Vasopressin also increased PtdBuOH production 4-5-fold (EC50 approx. 0.5 nM) and choline release (EC50 approx. 1 nM). The addition of a highly purified preparation of PLD (2-10 units/ml) from Streptomyces sp. to L6 cells stimulated a concentration-dependent increase in choline release and protein synthesis after both 90 min (maximum stimulation 13%) and 6 h (maximum stimulation 12%). PLD also stimulated RNA accretion after 6 h but not 90 min. The data support a role for PLD in the regulation of protein synthesis in L6 cells.

Animals↗
PubMed1992

Experience with high-dose radiation therapy and the intestinal sling procedure in patients with rectal carcinoma.

BACKGROUND: Surgery for Dukes' Stage B2 or C rectal carcinoma has a locoregional recurrence rate of 15-67%; this rate is significantly reduced when postoperative radiation therapy (RT) is given. However, RT contributes to radiation-associated small bowel injury in a dose-dependent manner. METHODS: Polyglycolic acid mesh used as an intestinal sling is able to keep the small bowel out of the pelvis during RT, thereby preventing radiation-associated small bowel injury. RESULTS: The authors reviewed the perioperative experiences and acute toxic effects of RT in 53 patients in whom the polyglycolic sling was placed from May 1985 through May 1990 during laparotomy for rectal malignancies (47 primary and 6 recurrent). There were 26 men and 27 women whose ages ranged from 34 to 88 years (mean, 64.7 years). Mild postoperative ileus occurred in most patients, and one patient had an anastomotic leak with a pelvic abscess. Bowel displacement from RT portals was confirmed using radiologic contrast studies. Forty-three patients with primary tumors have completed postoperative RT, and a mean of 5174 cGy has been administered. CONCLUSIONS: After 1-6 years of follow-up (mean, 2.1 years), eight patients have died of systemic disease. There were no cases of radiation-associated small bowel injury and only two cases of pelvic recurrence from primary rectal adenocarcinoma (5%).

Adult↗