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Biomedical subjects

A Craig

Publications and source records attributed to A Craig.

At least 73 records · Page 4Linked to original sources
PubMed1995

Mammalian gonadotropin-releasing hormone (GnRH) identified by primary structure in Russian sturgeon, Acipenser gueldenstaedti.

The mammalian form of gonadotropin-releasing hormone (GnRH) was purified from the brains of Russian sturgeon, Acipenser gueldenstaedti, using reversed-phase high pressure liquid chromatography (HPLC). The total concentration of mGnRH within these fish was 5.4 ng/brain. Small amounts of immunoreactive chicken GnRH-II like molecules were also detected but at insufficient quantities for purification. The primary structure of mGnRH was determined using automated Edman degradation. Because sequence data could not be obtained until after digestion by bovine pyroglutamyl amino-peptidase, it was determined that the amino-terminal residue was modified. Furthermore, mass spectrometric data and co-elution with synthetic mGnRH on HPLC confirmed that the carboxy-terminal residue was amidated. The amino acid sequence of sturgeon GnRH is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2.

Amino Acid Sequence↗
PubMed1995

Influences of dietary and intraduodenal lipid on alertness, mood, and sustained concentration.

The effects of intraduodenal and dietary lipid on alertness, mood and performance in a task requiring sustained attention were investigated in two studies. The first experiment compared the effect of duodenal infusion of either 100 g/l Intralipid (8.36 kJ/min) or isotonic saline (9 g NaCl/l) in paired studies carried out on two non-consecutive days on five male volunteers. Two consecutive 3 h infusions, one of lipid, the other saline, were given blind on each day using a crossover design. Analysis of variance indicated that lipid significantly reduced alertness (P < 0.05) and affected the speed and accuracy of performance in a sustained attention task (P < 0.05). A second experiment compared the effects on eight male volunteers of two isoenergetic lunches of similar appearance, taste and protein content but differing fat and carbohydrate (CHO) contents (fat energy:CHO, 64:18 v. 7:76). Alertness was lower (P < 0.05) and responses to stimuli in a sustained attention task were slower after the high-fat meal than after the low-fat meal (P < 0.05). In conclusion, infusion of lipid into the small intestine, and the substitution of fat for carbohydrate while keeping energy and protein constant in a lunch, both cause an enhanced postprandial decline in alertness and concentration. This may be related to the presence of lipid in the small intestine.

Adult↗
PubMed1994

Benzo[a]pyrene-resistant MCF-7 human breast cancer cells. A unique aryl hydrocarbon-nonresponsive clone.

Wild-type MCF-7 human breast cancer cells were cultured for 3 months in 1 microM benzo[a]pyrene (BaP), and resistant clones were screened for inducibility of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One of the BaP-resistant (BaPR) clones exhibited unique genotypic expression which distinguished it from both wild-type and drug-resistant (AdrR) variant MCF-7 cells. Glutathione levels, glutathione S-transferase activities, estrogen receptor levels, estrogen responsiveness, and expression of the multidrug-resistant MDR1 and MRP mRNA levels were similar in the wild-type and BaPR cells, whereas these parameters were reported to be altered in AdrR cells. In contrast, TCDD induced CYP1A1 gene expression and inhibited selected estrogen-induced responses in wild-type but not BaPR MCF-7 cells. Treatment of wild-type and BaPR cells with [3H]TCDD resulted in formation of the radiolabeled aryl hydrocarbon (Ah) 6 S nuclear receptor complex in both cell lines. The loss of Ah responsiveness in the BaPR variant cells correlated with the failure of the nuclear or transformed cytosolic Ah receptor complex to bind genomic dioxin-responsive elements as determined in gel retardation assays.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Relative sensitivities of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Cyp1a-1 and Cyp1a-2 gene expression and immunotoxicity in female B6C3F1 mice.

Improvements in risk assessment require better linkage of exposure to response by the determination of target tissue dose. The relative sensitivity of several responses in female B6C3F1 mice was compared on the basis of administered and target tissue dose spanning 3 orders of magnitude. Twenty-four hours after administration, [3H]TCDD was detected in the heart, spleen, kidney, uterus, thymus, lung, and liver, and the highest concentrations were noted in the liver, uterus, and lung. At doses from 5 to 25 ng/kg, hepatic [3H]TCDD levels associated with the cytosolic and nuclear subcellular fractions increased from 12 to 62% of the total liver levels and then decreased at higher doses. At the two lowest doses used in the enzyme induction study, 5 and 10 ng/kg, the levels of specifically bound nuclear Ah receptor complex liganded with [3H]TCDD were 2.3 and 2.5 fmol/mg protein. Slightly higher levels of nuclear Ah receptor complex were observed at doses between 25 and 100 ng/kg (i.e., 3.6 to 4.2 fmol/mg protein) and a steep dose-dependent increase in nuclear Ah receptor levels was noted at doses of 500, 1000, and 5000 ng/kg (8.0, 39.3, and 92.8 fmol/mg protein, respectively). The dose-dependent effects of [3H]TCDD on hepatic Cyp1a-1 and Cyp1a-2 mRNA levels, ethoxyresorufin O-deethylase (EROD) activity, and the splenic antibody plaque-forming cell (PFC) response to sheep red blood cells were also determined; the latter response was determined 9 days after administration of TCDD. Statistically significant induction of hepatic Cyp1a-1 was observed at lower doses (25 ng/kg) than any other marker, followed by induction of EROD and PFCs expressed per spleen or per 10(6) cells which was observed at 100 ng TCDD/kg and at higher doses. Cyp1a-2 was elevated significantly relative to control at doses > or = 1000 ng/kg. The ED50 value for PFCs/10(6) cells was the lowest of the variables analyzed and was not statistically significantly different from control (91 +/- 92 ng/kg). A 50% increase in Cyp1a-2 and Cyp1a-1 mRNA levels was observed at doses of 736 +/- 132 and 1630 +/- 431 ng/kg, respectively. Due to variability in response in PFCs/spleen and the submaximal induction of EROD activity, ED50 values could not be calculated for these responses. The analyses indicate that the immunosuppressive response (when normalized for the number of spleen cells) may be depressed by administered doses as low as 90 ng TCDD/kg body weight. A 50% increase in Cyp1a-1 or Cyp1a-2 was observed at higher administered doses (1630 or 736 ng/kg, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Immunosuppressive and monooxygenase induction activities of highly chlorinated diphenyl ether congeners in C57BL/6 and DBA/2 mice.

The dose-response effects of 2,2',3,3',4,5,5',6,6'-2,2',3,3',4,4',5,6,6'- and 2,2',3,3',4,4',5,5',6- nonachlorodiphenyl ether (non-aCDE) and decachlorodiphenyl ether (decaCDE) on the splenic plaque-forming cell (PFC) response to sheep red blood cells (SRBCs) and the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was determined in aryl hydrocarbon (Ah)-responsive C57BL/6 and less Ah-responsive DBA/2 mice. All the congeners exhibited immunotoxicity at doses between 2.5 and 10 mumol/kg in C57BL/6 mice whereas in DBA/2 mice doses > or = 25 mumol/kg were required to cause inhibition of the PFC response to SRBCs. The results also showed that the nonaCDE isomers and decaCDE were more active as inducers of hepatic EROD activity in C57BL/6 than DBA/2 mice; however, there was not a correlation between the induced EROD activity and the CYP1A1 and CYP1A2 mRNA levels in the C57BL/6 mice. These data suggested that the immunotoxicity of these compounds was mediated through the Ah receptor. However, the results showed that the immunotoxicity of the nonaCDE isomers and decaCDE was unexpectedly high compared to that of lower chlorinated diphenyl ethers and there were no apparent structure-activity relationships among the higher chlorinated congeners. This suggests that some of the immunosuppressive effects observed for the nonaCDE isomers and decaCDE may be Ah receptor-independent.

Animals↗
PubMed1993

ICAM-3 interacts with LFA-1 and regulates the LFA-1/ICAM-1 cell adhesion pathway.

The interaction of lymphocyte function-associated antigen-1 (LFA-1) with its ligands mediates multiple cell adhesion processes of capital importance during immune responses. We have obtained three anti-ICAM-3 mAbs which recognize two different epitopes (A and B) on the intercellular adhesion molecule-3 (ICAM-3) as demonstrated by sequential immunoprecipitation and cross-competitive mAb-binding experiments. Immunoaffinity purified ICAM-3-coated surfaces were able to support T lymphoblast attachment upon cell stimulation with both phorbol esters and cross-linked CD3, as well as by mAb engagement of the LFA-1 molecule with the activating anti-LFA-1 NKI-L16 mAb. T cell adhesion to purified ICAM-3 was completely inhibited by cell pretreatment with mAbs to the LFA-1 alpha (CD11a) or the LFA-beta (CD18) integrin chains. Anti-ICAM-3 mAbs specific for epitope A, but not those specific for epitope B, were able to trigger T lymphoblast homotypic aggregation. ICAM-3-mediated cell aggregation was dependent on the LFA-1/ICAM-1 pathway as demonstrated by blocking experiments with mAbs specific for the LFA-1 and ICAM-1 molecules. Furthermore, immunofluorescence studies on ICAM-3-induced cell aggregates revealed that both LFA-1 and ICAM-1 were mainly located at intercellular boundaries. ICAM-3 was located at cellular uropods, which in small aggregates appeared to be implicated in cell-cell contacts, whereas in large aggregates it appeared to be excluded from cell-cell contact areas. Experiments of T cell adhesion to a chimeric ICAM-1-Fc molecule revealed that the proaggregatory anti-ICAM-3 HP2/19 mAb was able to increase T lymphoblast attachment to ICAM-1, suggesting that T cell aggregation induced by this mAb could be mediated by increasing the avidity of LFA-1 for ICAM-1. Moreover, the HP2/19 mAb was costimulatory with anti-CD3 mAb for T lymphocyte proliferation, indicating that enhancement of T cell activation could be involved in ICAM-3-mediated adhesive phenomena. Altogether, our results indicate that ICAM-3 has a regulatory role on the LFA-1/ICAM-1 pathway of intercellular adhesion.

Antibodies, Monoclonal↗
PubMed1993

The influence of spinal cord injury on coping styles and self-perceptions: a controlled study.

Well-controlled research investigating psychological responses following Spinal Cord Injury (SCI) is lacking. In addition, much of the literature is based on depression following SCI and is dominated by data from the USA. The effects of SCI on perceptions of control, self-esteem and coping styles over the first year of SCI were investigated. Forty-one acute spinal injured patients and 41 able-bodied controls matched for age, sex and education completed a variety of standardised questionnaires on three occasions over one year. The instruments included the Locus of Control of Behaviour Scale, Rosenberg's Self-Esteem Scale, and an adapted Mental Adjustment to Cancer (MAC) Scale which measures coping styles, including fighting spirit, helplessness/hopelessness and fatalism. The SCI group were found to be more external in their perceptions of control, lower in self-esteem, and more helpless/hopeless and fatalistic in attitude than the controls. The majority of the SCI group had scores reflecting adaptive coping styles and intact levels of self-esteem but there were still a substantial proportion who displayed maladaptive coping styles (e.g. external locus of control, fatalism, helplessness). No differences in scores across time were found for either group. Implications for psychological rehabilitation are discussed.

Adaptation, Psychological↗
PubMed1992

Divalent cation regulation of the function of the leukocyte integrin LFA-1.

The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA-1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a manner that favors ligand binding. Since Mn2+ also promotes functional activity of other integrins, parallels in mechanism of ligand binding may span the integrin family. In contrast, induction of 24 epitope expression by Mg2+ required removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory effects upon LFA-1 function. The implication of our findings is that Ca2+ bound with relatively high affinity to LFA-1 may serve to maintain an inactive state. Thus induction of function and 24 epitope expression may occur as a result of displacement of Ca2+ from leukocyte integrins or alternatively, such activators may be able to impose the required conformational change in the presence of bound Ca2+.

Animals↗
PubMed1992

Leukocyte integrin activation.

Certain stages of the immune response require interaction of leukocytes with each other and with non-hematopoietic cells. One of the systems implicated in these interactions involves an integrin, LFA-1 (Lymphocyte Function Antigen-1), expressed by all leukocytes at their cell surface, and a molecule belonging to the immunoglobulin superfamily, ICAM-1 (Intercellular Adhesion Molecule-1). The avidity of LFA-1 for ICAM-1 is transient. It is modulated both by regulation of ICAM-1 expression and by activation of LFA-1 molecules constitutively expressed on leukocyte membranes. This activation, which induces a conformational change in the molecule, depends on the presence of divalent cations, notably Mg++. This has been demonstrated by using a specific monoclonal antibody, MAb 24. In addition to being a ligand for LFA-1, ICAM-1 is sometimes used as a cell receptor by pathogens such as Plasmodium falciparum, the causative organism of malaria. Very careful study of the binding site of this pathogen using specific antibodies, mutagenesis studies and the construction of a three-dimensional model of the molecule suggests some interesting therapeutic possibilities for the treatment of malaria.

CD3 Complex↗
PubMed1991

Perceptual and statistical analysis of cardiac phase and amplitude images.

A perceptual experiment was conducted using cardiac phase and amplitude images. Estimates of statistical parameters were derived from the images and the diagnostic potential of human and statistical decisions compared. Five methods were used to generate the images from 75 gated cardiac studies, 39 of which were classified as pathological. The images were presented to 12 observers experienced in nuclear medicine. The observers rated the images using a five-category scale based on their confidence of an abnormality presenting. Circular and linear statistics were used to analyse phase and amplitude image data, respectively. Estimates of mean, standard deviation (SD), skewness, kurtosis and the first term of the spatial correlation function were evaluated in the region of the left ventricle. A receiver operating characteristic analysis was performed on both sets of data and the human and statistical decisions compared. For phase images, circular SD was shown to discriminate better between normal and abnormal than experienced observers, but no single statistic discriminated as well as the human observer for amplitude images.

Analysis of Variance↗
PubMed1991

Voluntary blood pressure control by biofeedback: relationship to psychological characteristics.

1. Psychological characteristics were studied in 25 hypertensives (mean and standard deviation of blood pressure 150/95 +/- 12/5 mmHg), who received blood pressure (BP) biofeedback (BFB). Personality factors and success in BFB-BP modifying ability were correlated and the predictive value of psychological factors was estimated. 2. Questionnaires consisted of a Locus of Control of Behaviour (LCB) scale, the Spielberger state trait anxiety inventory and the Framingham Type A personality inventory. 3. BP was monitored continuously from the finger by volume clamp plethysmography during eight BFB sessions, each with three trials of raising, ignoring and lowering systolic blood pressure (SP). 4. SP was raised/lowered by 12 +/- 11/6 +/- 9 mmHg and heart rate (HR) increased by 10 +/- 3.9/+ 1 +/- 6.1. Ten subjects were able to lower SP by greater than or equal to 5 mmHg (15 +/- 7.5) and raise it by 17 +/- 11. The others achieved no decrease in SP and were also less successful at raising (8 mmHg, P = 0.04). 5. Changes in LCB and trait anxiety correlated with DP rise, whereas type A and pre-study state anxiety correlated with rising HR. Lowering of SP correlated weakly with change in LCB (r = 0.47, P = 0.06). 6. Combinations of psychological factors had independent predictive value for BP and HR change: trait anxiety (P = 0.03) and change in LCB (P = 0.009) with rise in diastolic blood pressure (DP); type A (P = 0.009), pre-study LCB (P = 0.02) and pre-study state anxiety (P = 0.01) with HR rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Biofeedback, Psychology↗
PubMed1990

An investigation into the relationship between anxiety and stuttering.

The relationship between self-reported anxiety and stuttering was explored. Although previous research has mostly shown that persons who stutter are no more anxious than persons who do not stutter, many of these studies had inadequate power to detect significant differences. In this study, a large number of stutters were assessed on state and trait anxiety before, and on trait anxiety after, intensive behavioral treatment. Their levels of anxiety were compared to those of nonstuttering controls matched for gender, age, and occupational status. Results showed that persons who stutter had significantly higher levels of fear (state anxiety) in a demanding speech situation. They were also shown to have higher levels of chronic anxiety (trait anxiety) than matched controls. However, trait anxiety measured after treatment was within normal levels. Although not allowing the conclusion that anxiety causes stuttering, these results do have important implications for the management of the disorder.

Adult↗
PubMed1990

Type I protein S deficiency and skin necrosis.

A kindred with Type I protein S deficiency is described in which the index case developed skin necrosis during induction of oral anticoagulant therapy for deep venous thrombosis. Two other family members with protein S deficiency have been detected, and demonstrate the clinical variability of this condition.

Acenocoumarol↗
PubMed1990

Ingrowing toenails: improving treatment.

Sixty-six patients with ingrowing toenails were randomly assigned to one of two treatment groups and followed up for 16 to 30 months after surgery. In group A 39 nail edges in 32 patients were treated by excision of the nail edge and chemical ablation of germinal matrix edge with 70% aqueous phenol. There were 34 patients in group B, in whom 46 nail edges and germinal matrix edges were surgically excised. In group A recurring symptoms developed in four (10%) nail edges, necessitating further surgery, and asymptomatic spicules developed in seven (18%) nail edges. Two (4%) nails in group B required reoperation and spicules developed in 10 (22%). Both procedures were performed as outpatient surgery, relieved pain and infection, and were acceptable to patients. At an average 2-year follow-up, both procedures yielded comparable results that were superior to those of simple avulsion.

Adult↗
PubMed1989

Central station data displays: an experimental evaluation of observer performance. Part 2: Factors affecting performance, and a comparison of analogue and digital data.

16 experienced ICU nurses monitored simulated central station VDU displays for the occurrence of ectopic beats and for signs of deterioration in general cardiovascular status. Each period of monitoring lasted for 1 h, and on separate occasions each nurse monitored 1, 2, 4 or 6 displays simultaneously. For primary clinical tasks, the data showed that the nurses' performance improved with each test. The identification of ventricular ectopic beats (VEBs) improved within the 1 h of each test except when 6 screens were being viewed simultaneously, with a similar result for the identification of deterioration of cardiovascular status. The nurses showed a marked preference for analogue signals over digits for the identification of VEBs. The highest priority clinical task was the identification of deteriorating cardiovascular status. When this task was performed efficiently less attention was given to minor tasks, and the nurse rated herself as very tired.

Attitude of Health Personnel↗