Search PubMed⌕ Search

Biomedical subjects

E L Harris

Publications and source records attributed to E L Harris.

At least 19 recordsLinked to original sources
PubMed1991

Using log-linear models to test for associations among congenital malformations.

Log-linear models can be used to test for pairwise associations and higher order interactions among anatomically distinct birth defects or congenital malformations. A log-linear model, including terms for every possible pairwise association among seven severe and easily detectable congenital malformations, was examined using data on 16,217 infants registered in the Metropolitan Atlanta Congenital Defects Program between 1968 and 1986. The resulting model showed clear patterns of strong association between some congenital malformations and not others, and the presence of 3-way interaction terms where the association between two malformations depended on the presence of a third. Examining a more parsimonious log-linear model showed overlapping patterns of pairwise association involving anal-rectal atresia and omphalocele, anal-rectal atresia and limb deficiency, and anal-rectal atresia and tracheaesophageal fistula. A second common pattern involved a triangular cluster with a hierarchical relationship among the three malformations (where there was a strong association between the first and second malformations and between the first and third malformations, but the association between the second and third was only seen in the absence of the first). Three such overlapping triangular clusters were identified from these data: neural tube defects, oral clefts, and omphalocele; neural tube defects, oral clefts, and limb deficiency; and limb deficiency, diaphragmatic hernia, and neural tube defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1991

Assessment of family history information in case-control cancer studies.

Evidence for the genetic basis of cancer has increased in recent years, and thus, assessing familial aggregation may play an important role in epidemiologic studies. To assess the degree to which family history variables are collected in cancer case-control studies, the authors conducted a literature review of studies published in six journals during 1982-1984. Only 25% of these included a family history component. The authors review some of the literature in favor of inclusion of family information and argue for its routine collection in cancer case-control studies.

Breast Neoplasms↗
PubMed1991

Familiality of breast cancer and socioeconomic status in blacks.

Familial patterns of the occurrence of breast cancer were studied in a population-based case-control series of black women from the Cancer and Steroid Hormone study. The risks of breast cancer among relatives of breast cancer cases were compared to those of controls who were matched for age and locale. Using the term "proband" to indicate either case or control status, significant predictors of risk to the relatives of probands included case/control status of the proband and the number of years of education completed by the proband. Genetic segregation analysis of the case families using external risks generated from SEER data indicated that the familial aggregation was consistent with Mendelian recessive transmission of a single major gene. The use of internally estimated risks, which are much less stable than the SEER risks, no longer permitted discrimination among the major locus models examined. To avoid possible reporting bias, we also performed segregation analysis on families of probands who had completed at least 12 years of education. The results from this analysis reflected the results from the entire data.

Adult↗
PubMed1991

Exclusion of linkage between familial Mediterranean fever and the human serum amyloid A (SAA) gene cluster.

We studied the relationship between the autosomal recessive trait familial Mediterranean fever (FMF) and the serum amyloid A (SAA) genes by comparing alleles of a highly polymorphic dinucleotide repeat and a conventional restriction fragment length polymorphism (RFLP) in the SAA gene cluster in Israeli FMF kindreds. By haplotype analysis, our data indicate a minimum crossover frequency of 22% between the SAA gene marker and FMF. By conventional linkage analysis this eliminates a minimum of 10.4 cM including and surrounding the SAA gene cluster as the site of the FMF mutation although SAA proteins are prominent physiologic markers of the acute attacks.

Crossing Over, Genetic↗
PubMed1990

Differences in mitogenic responses to angiotensin II, calf serum and phorbol ester in vascular smooth muscle cells from two strains of genetically hypertensive rat.

Vascular smooth muscle cells cultured from spontaneously hypertensive (SHR), New Zealand genetically hypertensive (GH) rat strains and their control strains (Wistar-Kyoto (WKY) and normal Wistar (N) rats) were compared for mitogenic responses [( 3H]-thymidine incorporation) to angiotensin II (AII), fetal calf serum (FCS), and the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). SHR cells showed enhanced basal [3H]-thymidine incorporation and increased responses to all three factors. In contrast, basal and FCS-stimulated [3H]-thymidine incorporation was the same or less in GH than in N cells. However, DNA synthesis was greater in GH cells in response to AII, AII + TPA or FCS + TPA. These results suggest that vascular smooth muscle cells from both hypertensive rat strains display enhanced mitogenesis, but the enhancement occurs via different intracellular signalling pathways.

Angiotensin II↗
PubMed1990

Mitogenesis in cultured vascular smooth muscle cells from two rat models of hypertension in response to fetal calf serum and angiotensin II.

Hypertension may result from vascular hypertrophy or hyperplasia due to enhanced growth of vascular smooth muscle cells (VSMCs), which has been demonstrated in VSMCs from spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) rats. To determine whether this enhanced mitogenesis is peculiar to SHRs or a general phenomenon in genetic models of hypertension, we have measured indices of cell growth [3H]-thymidine uptake in VSMCs from SHRs and New Zealand genetically hypertensive (GH) rats and controls [WKY and normal Wistar (N) rats] cultured in fetal calf serum (FCS) or angiotensin II (Ang II, 0.1 microM) in either 3% heat-treated FCS or serum-free medium. SHR cell numbers increased faster in response to both mitogens compared to WKY rats. However, GH and N rat responses to FCS were the same. Ang II caused a significant but similar increase in cell numbers in both GH and N rat cells (i.e., Ang II caused hyperplasia in all four strains) but [3H]thymidine uptake was significantly greater in GH rat cells. Ang II increased the total well protein content but not protein normalized on cell number, i.e., no hypertrophic effect of Ang II was seen in these actively dividing cells. We conclude that (a) growth properties of VSMCs from rats with genetic hypertension vary between strains; the differences in growth may reflect strain-specific variation in the activity of intracellular signalling systems subserving mitogenesis; and (b) Ang II causes VSMC hyperplasia.

Angiotensin II↗
PubMed1990

Flow cytometric analysis of cell cycle of cultured aortic smooth muscle cells from two strains of genetically hypertensive rats.

The growth curves of aortic smooth muscle cells (SMCs) from spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar-Kyoto (WKY) rats, and genetically hypertensive (GH) rats and their normotensive outbred controls (N) were compared. The proportion of cells in the various phases of the cell cycle was measured by flow cytometry. SHR cells showed significantly shorter doubling time than WKY rat cells, but doubling times for GH and N rats did not differ and were nearly the same as for SHRs. SHRs showed significantly greater proportion of S-phase (DNA-synthesizing) cells compared to WKY rat cells in the exponential growth phase. No significant difference was observed between GH and N rats in the proportion of cells in other phases of the cell cycle. GH and N rat cells stopped dividing in fetal calf serum (FCS)-free Dulbecco's Modified Eagle Medium (DMEM), whereas SHR and WKY rat cells continued to progress through the cell cycle in serum-free DMEM. The responses of FCS-deprived-arrested cells to the addition of FCS were similar in GH and N rats. SHRs showed a prolonged increase in S-phase cells in response to FCS compared to WKY rat cells, but maximum effects were similar. Enhanced cell proliferation in SHRs is not present in the other hypertensive strain of rats and is not explained by a simple hyperresponse to FCS.

Animals↗
PubMed1989

Genetic control of variation in human gingival fibroblast proliferation rate.

Logarithmic proliferation rate (Days 1 to 6) of gingival fibroblasts derived from 15 pairs of monozygotic (MZ) and 9 pairs of dizygotic (DZ) human twins was compared under optimal and suboptimal growth conditions. Cell proliferation rates exhibited considerable variability among strains. For Caucasian donors (13 MZ, 6 DZ pairs) DZ twins demonstrated significantly greater (P less than 0.01) within-pair variance in cell proliferation rate compared to MZ twins when evaluated under optimal growth conditions. Heritability analysis indicated strong genetic control of proliferation rate of human gingival fibroblasts (HGF) under optimal growth conditions (1.0 +/- 0.67), whereas proliferation rate of HGF under suboptimal growth conditions revealed less genetic control (0.42 +/- 0.61). These findings emphasize the importance of carefully matching control and test HGF in assays dependent on cellular proliferation.

Adolescent↗
PubMed1988

A nurse-associated epidemic of cardiac arrests in an intensive care unit.

Review of 2219 admissions to an intensive care unit at a large urban hospital from 1983 to 1985 revealed an epidemic of cardiac arrests during the evening shift from January 1984 to March 1985. Of the 88 evening-shift cardiac arrests during this time, one specific nurse (Nurse 14) was the care giver for 57 (65%). Eight of ten epidemic-period patients who experienced shift-specific circadian recurrences of cardiac arrests were patients of Nurse 14. No therapeutic intervention and no other health care provider was as strongly associated with evening-shift cardiac arrests as was Nurse 14. Multiple logistic regression analysis demonstrated that when risk of cardiac arrest was adjusted for age, sex, severity of illness, and postoperative status, patients of Nurse 14 were 47.5 times more likely to experience arrest than were other nurses' patients. An expert determined that, compared with other nurses, the cardiac arrests among Nurse 14's patients were more likely to be consistent with unexplained hyperkalemia, to be unexpected in timing, and to be inconsistent with the clinical course. The epidemic ceased when Nurse 14 left employment at the intensive care unit in March 1985. Epidemiologic surveillance of adverse outcomes in health care settings is recommended.

Data Interpretation, Statistical↗
PubMed1988

Calcium efflux in cultured vascular smooth muscle cells from genetically hypertensive rats: effect of angiotensin II and vasopressin.

Control of cell calcium handling and transport may be abnormal in hypertension. We have studied calcium efflux rates in response to angiotensin II and vasopressin in cultured vascular smooth muscle cells from New Zealand genetically hypertensive rats and normotensive control rats. Calcium efflux with both peptides was time- and concentration-dependent and was significantly greater in cells from the genetically hypertensive rats (P less than 0.001, analysis of variance). In addition, mean +/- s.d. protein content (0.31 +/- 0.01 versus 0.28 +/- 0.02 mg/well, n = 48, P less than 0.001) and calculated total cell calcium (3.63 +/- 0.27 versus 2.86 +/- 0.32 nmol/mg protein, n = 16, P less than 0.005) were greater in genetically hypertensive rat cells. These data are consistent with the presence of abnormal cell calcium dynamics in hypertension in genetically hypertensive rats.

Angiotensin II↗
PubMed1986

Lactoferrin: affinity purification from human milk and polymorphonuclear neutrophils using monoclonal antibody (II 2C) to human lactoferrin, development of an immunoradiometric assay using II 2C, and myelopoietic regulation and receptor-binding characteristics.

Several investigators have now confirmed our original report demonstrating the myelopoietic suppressive activity of lactoferrin (LF) in vitro. In order to further clarify this activity, we used the recently produced and purified neutralizing antibody (II 2C) to LF to set up an immunoradiometric assay specific for LF and to affinity purify LF from lysates of peripheral blood polymorphonuclear neutrophils (PMN) obtained from healthy donors. Iron-saturated purified PMN LF was as active as iron-saturated affinity purified milk LF as a suppressor of the release of granulocyte-macrophage colony stimulating factors (GM-CSF) from mononuclear human peripheral blood leukocytes. The activities of both the PMN LF and milk LF were inactivated by preincubation with monoclonal anti-LF antibody (II 2C). In order to evaluate the methods of iron saturation of LF in vitro as measures of their functional activities, milk LF was iron saturated by four different methods, including ferric citrate, ferric ammonium sulphate, ferric chloride with nitriloacetate, and ferric chloride alone. The functional characteristics of all four preparations of LF saturated with iron in vitro were relatively equal and were more active than native LF. Resident mouse peritoneal macrophages separated into subpopulations of GM-CSF-producing cells by velocity sedimentation were evaluated for their LF-receptor binding capacity and for sensitivity to the suppression of GM-CSF release by LF. Iron saturated LF suppressed release of GM-CSF from only those fractions containing LF-receptor bearing cells, although not all fractions containing cells bearing receptors for LF responded to the suppressive activity of LF. These studies provide further evidence for the myelopoietic regulatory activity in vitro of PMN-derived LF, which is mediated through populations of mononuclear phagocytes having receptors for LF.

Animals↗
PubMed1986

Monoclonal antibody (II2C) to human lactoferrin inactivates the myelopoietic suppressive effect of human lactoferrin in vitro.

A mouse monoclonal antibody was prepared against purified and fully iron-saturated human breast milk lactoferrin (LF). This antibody was of the IgG1 subclass, and recognized LF biosynthesized in low-density normal human bone marrow cells and LF stored in normal human polymorphonuclear neutrophils. This antibody did not recognize purified and iron-saturated human transferrin. The antibody inactivated the suppressive effects of purified and iron-saturated human milk LF and LF present in crude extracts of normal polymorphonuclear neutrophils against the release of granulocyte-macrophage colony-stimulating factors from mononuclear blood leukocytes in vitro.

Animals↗