Search PubMed⌕ Search

Biomedical subjects

M Lawson

Publications and source records attributed to M Lawson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Intracellular calcium and calcineurin regulate neutrophil motility on vitronectin through a receptor identified by antibodies to integrins alphav and beta3.

Buffering of intracellular calcium ([Ca2+]i) or inhibition of the calcium/calmodulin-dependent phosphatase, calcineurin, results in neutrophils being unable to detach from vitronectin with a consequent loss of motility. Treatment of [Ca2+]i-buffered or calcineurin-inhibited neutrophils with monoclonal antibodies (MoAbs) to beta3 or alphav beta3 integrins allowed neutrophils to detach and restored motility. Quantitative immunofluorescence and flow cytometry showed that MoAbs specific for beta3, alphav, or alphav beta3 integrins bind to neutrophils. Immunolocalization studies using antibodies to the highly conserved cytoplasmic domains of alphav and beta3 also identified the receptor on neutrophils. Whereas antibodies to alphav, alphav beta3, and beta3 recognized the receptor in intact cells, only the beta3 MoAb immunoprecipitated the receptor from a neutrophil cell lysate. The alpha subunit co-immunoprecipitated by the beta3 antibody reacted with an antibody to alphav by Western blot. Peptide maps of V8 protease digests showed a strong similarity in alpha and beta chains precipitated by antibodies to beta3 from neutrophils and endothelial cells. These results indicate that [Ca2+]i and calcineurin regulate neutrophil motility on vitronectin through an alphav beta3-like receptor. Although we cannot rule out the possibility that neutrophils have an isoform of alphav, such an isoform would have to be similar enough to react with alphav- and alphav beta3-specific MoAbs in intact cells.

Amino Acid Sequence↗
PubMed1996

Application of ambulatory infusion devices in infusional cancer chemotherapy: a model for nursing management.

Optimal support of the patient receiving infusional cancer chemotherapy (ICC) in the home setting is partially dependent on the provision of an infusional device that offers minimal complexity and maximal reliability and safety. The selection of the appropriate device is vital to positive patient outcomes and to the comfort level of both patient and care providers. This article presents issues and considerations in the selection of infusion devices and the nursing role in the management of patients utilizing such devices. Aspects of nursing management are presented from the perspective of The Cancer Center of Boston (TCC) model.

Ambulatory Care↗
PubMed1995

Lack of effect of recombinant platelet-derived growth factor on human neutrophil function.

Platelet-derived growth factor (PDGF) has been reported to induce chemotaxis, degranulation, and superoxide anion generation, and to increase the expression of CD11b/CD18 in human neutrophils; hence, it has been proposed as an important regulator of neutrophil function. Most of the studies on PDGF, however, have been complicated by the use of nonrecombinant PDGF or the use of mixed leukocyte cell preparations. Assessment of the effects of recombinant human PDGF-AB or -BB which display agonist activity against both PDGF receptor subtypes failed to demonstrate any effect of this peptide on neutrophil shape change, respiratory burst activity, CD11/CD18, or CD62-L expression, inositol 1,4,5-trisphosphate accumulation, or phosphorylation of mitogen-activated protein kinase. This apparent lack of effect of PDGF was consistent with our findings that neutrophils display no specific 125I-PDGF-AB or -BB binding and lack detectable mRNA for PDGF alpha-receptor and beta-receptors. These data indicate that human neutrophils do not possess functional PDGF receptors and question previous reports of a functional effect of this peptide in these cells.

3T3 Cells↗
PubMed1995

Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans.

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.

Adult↗
PubMed1995

Hawksley random zero sphygmomanometer versus the standard sphygmomanometer: an investigation of mechanisms.

There has been recent controversy over the accuracy of the Hawksley random zero sphygmomanometer (RZS). In most instances, there has been a bias towards lower recordings with the RZS. In an attempt to identify the mechanism, we designed a study to test the hypothesis that biased error is due to: (1) the magnitude of the random zero; and (2) the magnitude of the pressure being recorded. A RZS (60 mm Hg zero UK version) was connected via a Y-tube to a standard mercury sphygmomanometer (SMS). The circumference of the cam responsible for the variable reservoir size in the RZS was marked into quarters. Within each 10 mm Hg band from 300 to 60 mm Hg, 12 paired readings were taken randomly: three within each of the four quarters of the cam circumference. The mean SMS value was 148.8 vs. 148.2 mm Hg for the RZS. Although of minimal biological significance this difference was highly significant (t = 6.2; p < 0.0001). Our findings fail to confirm the difference between RZS and SMS previously reported and we did not find any evidence of a relation in the difference between SMS and RZS and either the random zero value or the height of the blood pressure. Our findings suggest that if the RZS does under record BP versus the SMS it may relate to a patient-machine interaction not detectable in our system.

Blood Pressure Determination↗
PubMed1995

Absence of genetic linkage between polymorphisms of the insulin receptor gene and essential hypertension.

This study evaluated whether hypertensive siblings had excess sharing of RsaI and SstI alleles of the insulin receptor gene compared with a random population. Thirty families consisting of 60 affected individuals with established hypertension were genotyped for the RsaI and SstI restriction fragment length polymorphisms and the resulting genotype data was analysed using the affected pedigree member method of linkage analysis. The hypertensive siblings were found to have increased sharing of INSR alleles; however, this linkage could not be confirmed using a maximum LOD score method. Thus, the results from this study do not support a role for the INSR gene in the genesis of essential hypertension in the population studied.

Aged↗
PubMed1994

Linkage of the angiotensinogen gene to essential hypertension.

BACKGROUND: The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension. METHODS: Samples of DNA from 63 white European families in which two or more members had essential hypertension were tested for linkage of the angiotensinogen gene to this disorder. Affected cousins, nephews, nieces, and half-siblings were included when possible. To test for linkage, we used as a marker a dinucleotide-repeat sequence flanking this gene, and we employed the affected-pedigree-member method of linkage analysis. Two molecular variants of the angiotensinogen gene, one encoding threonine instead of methionine at position 235 (M235T) and the other encoding methionine rather than threonine at position 174 (T174M), were also tested for possible association with essential hypertension. RESULTS: We found significant linkage (t = 5.00, P < 0.001) and association (chi-square = 53.3, P < 0.001) of the angiotensinogen-gene locus to essential hypertension in the 63 multiplex families. This linkage was consistently maintained in the subgroup of subjects with diastolic pressure above 100 mm Hg and in the subgroups classified according to sex. It has been proposed previously that T174M and M235T are associated with essential hypertension. However, we found no association in our population between either polymorphism and this disorder. CONCLUSIONS: This study provides strong and consistent support for the linkage to essential hypertension of regions within or close to the angiotensinogen gene. Precisely how mutations in this region may result in hypertension remains to be determined.

Aged↗
PubMed1994

Effect of moderate dietary protein restriction on the progression of overt diabetic nephropathy: a 6-mo prospective study.

To assess whether moderate dietary protein restriction can delay the progression of overt diabetic nephropathy, 22 subjects with insulin-dependent diabetes mellitus were randomly assigned to an unrestricted protein diet (> 1.6 g.kg body wt-1.d-1) or a moderately protein-restricted diet (0.8 g.kg body wt-1.d-1) and followed prospectively for six mo. Direct isotope methods were used to assess renal function. Protein intake was assessed by measurement of urinary urea nitrogen. The two groups were well-matched for age, sex, duration of diabetes, glycemic control, blood pressure, and degree of renal insufficiency. Patients consuming the unrestricted protein diet (n = 11) showed a progressive decline in glomerular filtration rate of 1.3 mL.min-1.mo-1 with no change in proteinuria. Patients consuming the moderately protein-restricted diet showed a marked decrease in the degree of proteinuria (2.15-1.13 g/d, P = 0.036) and a stabilization of glomerular filtration rate. This occurred independently of changes in blood pressure or glycemic control. Moderate dietary protein restriction can ameliorate progression of overt diabetic nephropathy.

Adult↗
PubMed1994

Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps.

The metabolic activation of food-borne heterocyclic amines to colon carcinogens in humans is hypothesized to occur via N-oxidation followed by O-acetylation to form the N-acetoxy arylamine that binds to DNA to give carcinogen-DNA adducts. These steps are catalyzed by hepatic cytochrome P4501A2 (CYP1A2) and acetyltransferase-2 (NAT-2), respectively, which are known to be polymorphic in humans. On the basis of this proposed metabolic activation pathway, patients at greatest risk to develop colorectal cancer or nonfamilial polyps should be those who possess both the rapid NAT-2 and rapid CYP1A2 phenotypes and are exposed to high dietary levels of carcinogenic heterocyclic amines. Using a method that involves caffeine administration and high pressure liquid chromatographic analysis of urinary metabolites, we have determined the CYP1A2 and NAT-2 phenotypes of 205 controls and 75 cancer/polyp cases. Exposure information was obtained using a dietary and health habits questionnaire. Both the rapid CYP1A2 and rapid NAT2 phenotypes were each slightly more prevalent in cases versus controls (57% and 52% versus 41% and 45%, respectively). However, the combined rapid CYP1A2-rapid NAT-2 phenotype was found in 35% of cases and only 16% of the controls, giving an odds ratio of 2.79 (P = 0.002). Univariate analysis of the questionnaire indicated that age, rapid-rapid phenotype, and consumption of well done red meat were associated with increased risk of colorectal neoplasia. Furthermore, a logistic regression model that included age (as a continuous variable), consumption of well done red meat, and rapid-rapid phenotype as independent covariates gave odds ratios of 1.08, 2.08, and 2.91, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗