PubMed Health⌕ Search

Biomedical subjects

A Blackwood

Publications and source records attributed to A Blackwood.

12 recordsLinked to original sources

The formation of ceramide-1-phosphate during neutrophil phagocytosis and its role in liposome fusion.

Ceramide, a product of agonist-stimulated sphingomyelinase activation, is known to be generated during the phagocytosis of antibody-coated erythrocytes by polymorphonuclear leukocytes. Agonist-stimulated formation of ceramide-1-phosphate is now shown to occur in 32PO4-labeled neutrophils. Ceramide-1-phosphate is formed by a calcium-dependent ceramide kinase, found predominately in the neutrophil plasma membrane. The neutrophil kinase is specific for ceramide because, in contrast to the bacterial diglyceride kinase, ceramide is not phosphorylated under conditions specific for diglyceride phosphorylation. Conversely, 1,2-diacylglycerol does not serve as substrate for the neutrophil ceramide kinase. Ceramide kinase activation occurs in a time-dependent fashion, reaching peak activity 10 min after formyl peptide stimulation and challenge with antibody-coated erythrocytes. The lipid kinase activity is optimal at pH 6.8. Because the formation of the phagolysosome is a critical event in phagocytosis, the effect of ceramide-1-phosphate in promoting the fusion of liposomes was determined. Both the addition of increasing concentrations of sphingomyelinase D and ceramide-1-phosphate promoted liposomal fusion. In summary, ceramide-1-phosphate is formed during phagocytosis through activation of ceramide kinase. Ceramide-1-phosphate may promote phagolysosome formation.

Calcium↗

Organochlorine compounds (DDE and PCB) in plasma and breast cyst fluid of women with benign breast disease.

The organochlorines, dichloro-diphenyl-trichloroethane and polychlorinated biphenyl (PCB) are pervasive environmental contaminants. Results from previous studies have been conflicting regarding the relationship between the internal dose of these organochlorine residues and breast cancer risk. To determine whether these compounds are present in breast cyst fluids and whether cyst fluid and plasma concentrations are correlated, we analyzed organochlorines in paired cyst fluid and plasma samples from 24 subjects using gas chromatography and electron capture detection. All but one of the women had a history of multiple cysts, suggesting that they were at elevated risk for future breast cancer. DDE (a metabolite of dichloro-diphenyl-trichloroethane) was present in 22 of the cyst samples and PCB was detected in 19 of the cyst samples. Organochlorine levels were more concentrated in the plasma than in breast cyst fluids. Levels of DDE in plasma were significantly correlated with those in cyst fluid (r = 0.73; P < 0.001); in contrast to PCB levels in cyst and plasma (r = 0.37; P = 0.12). Congener specific analysis of the PCBs showed that some individual congeners were preferentially excluded from or concentrated in the cyst fluid. To our knowledge, this study is the first to demonstrate that PCB and DDE are present in cyst fluids and thus in contact with the ductal epithelium of the breast. These results support the use of plasma DDE as a proxy for DDE in the target tissue in research on the role of environmental factors in breast cancer.

Adult↗

Prediction of adolescent aggression by childhood personality measures: a comparison of projective procedures, self-report tests, and behavior ratings.

Projective procedures, self-report measures, and teacher behavior ratings were compared as to which type of assessment best predicted adolescent aggressive behavior 6 years after they were administered. A questionnaire that assesses aggressive behavior was given to 125 adolescents in grades seven through twelve who had been administered a variety of projective, self-report, and teacher ratings of aggression 5 years earlier. Their parents were given the same questionnaire. Controlling for sex, age, and academic ability, the results indicated that children's scores on the projective measures predicted aggressive behaviors 5 years later. In addition, projective procedures were at least as valid as the other types of assessments in predicting aggressive behaviors. Results suggest that criticisms of projective procedures may be addressed with continued efforts to evaluate their validity.

Adolescent↗

Angiotensin converting enzyme gene I/D polymorphism, blood pressure and the renin-angiotensin system in Caucasian and Afro-Caribbean peoples.

The objectives of this study were to assess relations between ACE gene I/D polymorphism, essential hypertension, plasma renin activity and aldosterone in white (European descent) and black (Afro-Caribbean descent) peoples. Measurements were carried out on a total of 320 subjects (210 white: 116 men, 94 women; 110 black: 65 men, 45 women); all were on their usual sodium intake; none was on anti-hypertensive therapy and none had secondary hypertension. Genomic DNA was isolated from blood cells and ACE I/D genotype was established using polymerase chain reaction. Plasma hormones were measured by radioimmunoassay and blood pressure (BP) with an ultrasound sphygmomanometer. All subjects were grouped into normotensive, borderline and hypertensive according to WHO guidelines. The distribution of the I/D genotype in the white people was approximately 1:2:1; by contrast, in the Afro-Caribbean people there was a significantly higher frequency of the D allele (chi 2P = 0.04). Within the white people there was no significant association between ACE genotype and high BP; however, within the black people there was a positive association between the frequency of the D allele and increasing BP ( chi 2 for trend P = 0.03). In either group, there were no associations between ACE I/D genotype and plasma renin activity and aldosterone suggesting that ACE genotype does not contribute to the expression of the circulating renin-angiotensin system. This study highlights differences in ACE I/D polymorphism between white and black peoples and suggests the possibility of racial differences in the association between ACE genotype and BP.

Adult↗

Hormonal and renal responses to neutral endopeptidase inhibition in normal humans on a low and on a high sodium intake.

Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2-4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4 +/- 5.5 mmol on the low sodium diet and 73.1 +/- 25.6 mmol on the high sodium diet; P < 0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibition.

Adult↗

Angiotensin converting enzyme insertion/deletion polymorphism: association with ethnic origin.

OBJECTIVE: To determine the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in several ethnic groups: Caucasian Europeans, Black Nigerians, Samoan Polynesians and Yanomami Indians. RESULTS: The ratio of the frequencies of the II, ID and DD genotypes were 1:2:1 in the Europeans, but there was a tendency towards a higher frequency of the D allele in the Nigerians. In contrast, the Samoans and the Yanomami Indians displayed a much higher frequency of the I allele than of the D allele. CONCLUSION: The relationship between ACE genotype and disease in these latter groups is still not known, but the present results clearly suggest that ethnic origin should be carefully considered in the increasing number of studies on the association between I/D ACE genotype and disease aetiology.

Alleles↗

Faecal bile acids and clostridia in patients with breast cancer.

We have studied 30 patients presenting with breast cancer and 36 control patients admitted to hospital for minor surgery. Stool specimens were obtained for bile acid analysis and bacterial nuclear dehydrogenation activity (NDC) estimation. The mean total faecal bile acid (FBA) concentration (mumol/g) in patients with breast cancer was 15.6 /+- 1.8 s.e., significantly lower than for control patients (20.5 /+- 1.9). NDC were isolated from the faeces of 58% of breast cancer patients an 15% of control patients, this difference being statistically highly significant (P less than 0.005). Increased bile-acid degradation by bacteria in the large bowel may explain the reduced FBA concentration in patients with breast cancer. Increased NDC isolation in breast-cancer patients suggests that oestrogen production in the colon may play a role in the aetiogy of breast cancer in some patients.

Adult↗

Massive pulmonary arteriovenous fistula in the newborn.

Although pulmonary arteriovenous fistula as a cause of cyanosis is well recognized, most of the reported cases occur in older children and adults, and its importance as a correctable lesion in the newborn is often overlooked. The details of two babies who presented with cyanosis in the first few days of life are presented to emphasize that this eminently treatable lesion may need to be managed as an emergency.

Arteriovenous Malformations↗

Establishing a cancer risk evaluation program.

PURPOSE: Presymptomatic genetic testing for cancer susceptibility is a new practice arena that raises many complex issues. This article presents one model of a cancer risk evaluation program that specifically addresses the unique issues associated with genetic testing for cancer risk. DESCRIPTION OF PROGRAM: The Cancer Risk Evaluation Program is designed to care for any individual concerned about his or her risk for cancer, offering predisposition genetic testing if appropriate. The program includes clinical and psychosocial assessment, education, cancer risk analysis, and genetic counseling; it offers long-term screening and surveillance and provides a forum for ongoing genetic and clinical research. RESULTS: Program evaluations from participants have shown that the program is successfully meeting the needs of the participants. This program also ensures that the University of Pennsylvania Cancer Center is delivering cancer genetic services consistent with the existing position statements on genetic testing for cancer susceptibility, which have included guidelines and indications for predisposition genetic testing and informed consent. CLINICAL IMPLICATIONS: Researchers anticipate a substantial demand for predisposition genetic testing for cancer susceptibility. However, not all individuals interested in testing are eligible or willing to undergo direct gene analysis because of the potential risks. Therefore, clinical programs must address the complex issues surrounding presymptomatic genetic testing and incorporate cancer risk assessment strategies. Additionally, healthcare providers in this new practice arena should be fully informed and current in the state of the knowledge regarding cancer risk assessment; predisposition genetic testing; and the ethical, legal, and social issues pertaining to cancer risk assessment and management.

Adult↗