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Biomedical subjects

A Carter

Publications and source records attributed to A Carter.

At least 55 records · Page 3Linked to original sources

Association of a common polymorphism in the factor XIII gene with myocardial infarction.

Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G-->T) in exon 2 of the A-subunit gene which codes for an amino acid change three amino acids from the thrombin activation site (Factor XIIIVal34Leu) is a candidate for a role in the pathogenesis of acute myocardial infarction. Factor XIII genotype frequencies were determined in a case-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary artery disease and were evaluated for a history of myocardial infarction. The prevalence of the mutation was lower in patients with myocardial infarction than without (32% vs. 50%), p = 0.0009 and than in controls (32% vs. 48%), p = 0.005. Patients possessing the mutation with a history of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genotype (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patients possessing wild type with MI compared to those without MI. These results indicate that the G-->T mutation coding for factor XIIIVal34Leu is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.

Case-Control Studies↗

Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production.

Interferon-gamma-inducing factor (IGIF, interleukin-18) is a recently described cytokine that shares structural features with the interleukin-1 (IL-1) family of proteins and functional properties with IL-12. Like IL-12, IGIF is a potent inducer of interferon (IFN)-gamma from T cells and natural killer cells. IGIF is synthesized as a biologically inactive precursor molecule (proIGIF). The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1). The Asp-X sequence at the putative processing site in proIGIF suggests that a protease such as caspase-1 might be involved in the maturation of IGIF. Here we demonstrate that caspase-1 processes proIGIF and proIL-1beta with equivalent efficiencies in vitro. A selective caspase-1 inhibitor blocks both lipopolysaccharide-induced IL-1beta and IFN-gamma production from human mononuclear cells. Furthermore, caspase-1-deficient mice are defective in lipopolysaccharide-induced IFN-gamma production. Our results thus implicate caspase-1 in the physiological production of IGIF and demonstrate that it plays a critical role in the regulation of multiple proinflammatory cytokines. Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action.

Animals↗

Effect of hepatocyte growth factor on early human haemopoietic cell development.

Hepatocyte growth factor (HGF) stimulates cell proliferation, differentiation and migration by binding to its receptor, MET R. Whether the HGF/MET R axis plays an important regulatory role in human haemopoietic cell growth is an unresolved issue. To investigate this situation, we employed several complementary strategies including RT-PCR, FACS analysis, and mRNA perturbation with oligodeoxynucleotides (ODN). We found that very primitive, FACS sorted, CD34+ Kit+ marrow mononuclear cells (MNC) failed to express RT-PCR detectable MET R mRNA. In contrast, MET R expression was easily detectable by RT-PCR in marrow stroma fibroblasts, in cells isolated from BFU-E and CFU-GM colonies, and in unselected normal MNC. Subsequent FACS analysis revealed that MET R protein was detectable on approximately 5% of the latter cells. HGF, at concentrations of 1-50 ng/ml, had no demonstrable effect on survival or cloning efficiency of normal CD34+ MNC in serum-free cultures. Antisense ODN mediated perturbation of MET R mRNA expression in normal CD34+ MNC, with FACS documented decline in protein expression, had no effect on the ability of these cells to give rise to haemopoietic colonies of any lineage. We also examined the biology of HGF/MET R expression in malignant haemopoietic cells. Using the strategies described above, we found that MET R mRNA was expressed in many human haemopoietic cell lines, and that the protein was expressed at high levels on HTLV transformed T lymphocytes. Wild-type CML and AML blast cells also expressed MET mRNA, and HGF was able to co-stimulate CFU-GM colony formation in approximately 20% of cases studied. Therefore, although the HGF/MET R axis appears to be dispensable for normal haemopoietic cell growth, it may play a role in the growth of malignant haemopoietic progenitor cells.

Cell Line↗

Ritual, habit, and perfectionism: the prevalence and development of compulsive-like behavior in normal young children.

Young children engage in a significant amount of ritualistic, repetitive, and compulsive-like activity that appears to be part of their normal behavioral repertoire. Empirically, little is known about the onset, prevalence, and developmental trajectory of these phenomena. A parent-report questionnaire, the Childhood Routines Inventory (CRI), was developed to assess compulsive-like behavior in young children, and was administered to 1,492 parents with children between the ages of 8 and 72 months. The CRI has strong overall internal consistency and a distinct two-factor structure. The frequency of compulsive-like behaviors changes with age: Two-, 3-, and 4-year-olds engaged in more compulsive behavior than children younger than 1 year of age and older than 4 years of age. Results are discussed from a developmental psychopathology framework and for their implications for future research in this area.

Child↗

Characterisation of vha26, the Drosophila gene for a 26 kDa E-subunit of the vacuolar ATPase.

A Drosophila melanogaster gene and cDNA for the E-subunit of the V-ATPase were characterised. The deduced product has 226 amino acids and a molecular mass of 26.1 kDa. The gene is a single copy at 83B1-4 on chromosome 3R. The coding sequence is punctuated by three introns which do not align with those in Neurospora. The gene is ubiquitously expressed as an mRNA of 2.3 kb. but at lower levels in pupae.

Amino Acid Sequence↗

Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells.

Tumour necrosis factor (TNF)-alpha exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-alpha-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-alpha-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-alpha-induced autocrine growth. In contrast, the TNF-alpha-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-alpha on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-alpha-signalled growth inhibition is exclusively transduced via TNF-Rp55.

Adolescent↗

Estradiol alters ethanol-induced effects on beta-endorphin and met-enkephalin levels in specific brain regions of ovariectomized rats.

The present investigation was conducted to evaluate the effects of estradiol on ethanol-induced alterations of beta-endorphin (beta-EN) and met-enkephalin (ME) levels in specific brain regions of ovariectomized rats. Female Sprague-Dawley rats (100-124 g) adapted to a 12-hour light, 12-hour dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 14 days, ethanol (3 g/kg as 22.5% solution in saline, i.p.), estradiol (50 micrograms/kg in 0.2 ml of olive oil, s.c. in the dorsal neck region), or a combination of ethanol and estradiol were administered to rats at 11:00 h. Control animals were injected intraperitoneally with 2 ml saline and subcutaneously with 0.2 ml olive oil. Animals were sacrificed by decapitation 2 h later. The brains were immediately removed; the cortex, hippocampus, hypothalamus, and midbrain were dissected and their beta-EN and ME levels were measured by radioimmunoassay. Ethanol administration significantly decreased both beta-EN and ME levels in the hypothalamus. Administration of estradiol alone also resulted in a significant decrease in beta-EN and ME levels in the hypothalamus. Additionally, concurrent administration of ethanol and estradiol showed a decrease in the levels of beta-EN and ME in the hypothalamus. Co-administration of ethanol with estradiol also caused a significant decrease in the levels of beta-EN in midbrain. However, ME levels were increased in the midbrain after concurrent administration of estradiol and ethanol. ME levels also increased in the hippocampus and cortex after co-administration of estrogen and ethanol. These results clearly indicate that estradiol significantly alters ethanol-induced effects on beta-EN and ME levels in specific brain regions of ovariectomized rats. The present findings may in part explain sex differences in alcohol effects.

Animals↗

Recurrent transitional cell carcinoma arising within an ileal conduit following cystectomy. A case report and review of the literature.

Recurrent transitional cell carcinoma arising within an ileal conduit following cystectomy for malignant disease is rare. We report on a case in which such a recurrence occurred, well away from the ureteroileal anastomosis and without coexisting upper tract involvement. The possible pathogenesis of these recurrences is discussed and the existing literature reviewed. Although uncommon, the possibility of recurrence within a conduit should be considered in any patient who presents with haematuria following a resection for malignant disease.

Aged↗

Addressing a neglected coronary heart disease risk factor in an HMO: exercise counseling and fitness testing at group health cooperative.

Group Health Cooperative, following the lead of the American Heart Association (AHA), the Centers for Disease Control (CDC), and the US Preventive Services Task Force (USPSTF), has identified inactivity as one of the most significant risk factors for the prevention of coronary heart disease (CHD). This paper reports on the programs being developed at Group Health Cooperative to address inactivity. A clinical tool designed to make fitness testing and comprehensive exercise counseling practical in routine primary care was designed and piloted. The fitness test was based on the One-Mile Walk Test, with computerization of the results analysis and reporting. The test helped the physician assess the patient's current exercise habits and physical fitness in terms of Vo2max (maximal oxygen consumption). The computer program showed the patient and the physician how the individual's Vo2max compared to norms for the patient's age and gender. The program provided comprehensive written exercise counseling and individualized advice about activity and fitness based on the patient's current exercise habits. The test cost little to administer, and helped reduce the time and effort of the primary physician in providing exercise counseling, while making optimal use of the physician's power to motivate. Exercise counseling is a very cost-effective preventive intervention. We believe that an organized and systematic exercise counseling program, together with a program for measuring fitness, would be the most effective intervention. Evidence indicates that effective exercise counseling should result in substantial reduction in disease in our population.

Adult↗

What's happening with consumer participation?

Consumer empowerment, both individually and within the service, is a growing trend in mental health. This trend is such that consumers are having more input into the service being provided. Shared control is a wave of the future, thereby increasing consumer empowerment not only within the service but within our own lives. The road is long and there are many bumps along the way for both the consumer and the health worker, yet the results of consumers leading quality lifestyles gives other consumers hope that they too can be capable of being active participants rather than relying on others to take care of them.

Consumer Advocacy↗

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia.

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.

Actuarial Analysis↗

A correlation between the expression of the bcr-abl chimeric gene and severity of the clinical state of CML patients with time.

Using the reverse polymerase chain reaction, four Ph' positive CML patients were followed for 2 years; a correlation between the severity of the clinical state and the b3a2 expression was noted with time. Additionally, amplification of the c-myc proto-oncogene was observed, using Southern blot analysis, in one patient prior to his entry to the blast phase. No reorganization of the bcr-abl rearrangement site was found in the latter patient. The data suggest that a routine follow-up of CML patients using the Southern blot analysis and the reverse transcription-polymerase chain reaction might be of importance in evaluating the progression of the disease.

Adult↗