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L Morrison

Publications and source records attributed to L Morrison.

At least 55 records · Page 3Linked to original sources
PubMed1998

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

AIDS Vaccines↗
PubMed1998

Spontaneous abortions are reduced after preconception diagnosis of translocations.

PURPOSE: Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11). METHODS: The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added. RESULTS: A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%). CONCLUSIONS: With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1998

Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21.

Fluorescence in-situ hybridization (FISH) for application in preimplantation genetic diagnosis (PGD) of aneuploidy has been used successfully, but stringent scoring criteria to score FISH signals have not been developed. In the present study a FISH protocol to simultaneously enumerate chromosomes X, Y, 13, 16, 18, and 21 was used to evaluate two different scoring criteria. The criteria consider hybridization signal size, shape, and vicinity to other signals and nuclear diameter. For this purpose, 74 embryos (412 blastomeres) donated for research had most or all of their cells analysed. The least error-prone criterion (9%) was selected for use in PGD cases. Some probes produced more errors than others, and these criteria may provide clues to improve these probes. The same probe solution was applied to 55 PGD cases and a total of 307 embryos. Of the non-transferred embryos, 67 were fully reanalysed and 1.5% (1/67) of them were falsely diagnosed as normal, while 19% (13/67) were falsely diagnosed as abnormal. Twelve of the patients became pregnant after PGD.

Aneuploidy↗
PubMed1997

Beds not bombs.

Explore the source record for details and available documents.

Global Health↗
PubMed1997

Epidemiology of nematodosis in Romney lambs selectively bred for resistance or susceptibility to nematode infection.

Field trials were undertaken to compare nematode population dynamics, lamb productivity and levels of breech soiling in experimental flocks of Romney lambs selectively bred for increased resistance or susceptibility to nematode infection. In each year of the 2 year study, spring-born ewe lambs derived from Wallaceville Animal Research Centre's divergent nematode-resistant and nematode-susceptible breeding lines were grazed as separate flocks on matched farmlets from weaning (at 3 months old) until they were approximately 10-11 months old. Allocation of farmlets was reversed between Years 1 and 2 of the study to account for any possible paddock-related effects. Within each year both flocks were subjected to identical management conditions, including anthelmintic treatment (which was administered only when the overall mean faecal worm egg count measured across both genotypes reached 1500 eggs g-1). In both years, by mid-autumn (April) nematode larval infestation levels on pasture were approximately 5-6-fold greater on the farmlet grazed by susceptible (S) genotype lambs than on that grazed by their resistant (R) counterparts (Year 1: 2506 cf. 544 larvae kg-1 herbage; Year 2: 431 cf. 74 larvae kg-1 herbage). This led to 51-fold and 56-fold differences in faecal egg count between R and S lambs by late autumn (May) and winter (July) in Years 1 and 2, respectively. Although mean growth rates were similar in the R and S lambs over summer (while pasture infestation levels on the farmlets were still in the process of diverging), significantly higher growth rates occurred in the R than in the S lambs over autumn-winter in both years of the study (P < 0.01). In contrast, no significant differences in growth rate occurred in either year between male lambs derived from the nematode-resistant and nematode-susceptible breeding lines which were grazed together on another area of the Wallaceville farm from weaning until late autumn. Despite the substantially lower pasture infestation levels encountered by the R ewe lambs, they nevertheless temporarily suffered more breech soiling (dags) than their S counterparts (P < 0.01) in both years. Yearling fleece-weights of the R and S genotypes did not differ significantly in either year. Although the results of our study confirmed that there are potentially significant epidemiological benefits to be derived from breeding sheep for resistance to nematode infection, these benefits did not appear to be associated with large advantages in animal performance. Further work is needed to establish how these results should be interpreted with respect to anthelmintic drench requirements of genetically resistant animals.

Animals↗
PubMed1997

Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians.

BACKGROUND: We evaluated the association among the M235T and T174M variants of the angiotensinogen (AGT) gene, plasma AGT, and hypertension status in a sample of Nigerians. METHODS AND RESULTS: Participants were selected from the extremes of the blood pressure distribution obtained from the population survey of 2509 men and women aged 25 to 74 years. Cases (hypertensive subjects) were individuals who had high blood pressure or were taking antihypertensive medication, and control subjects were individuals with low blood pressure who had never taken antihypertensive medication. We found a significant association between the M235T variant and plasma AGT level. Hypertensive subjects had higher plasma AGT levels compared with control subjects. The allele frequencies of the two variants were similar in the hypertensive patients and the control subjects. CONCLUSIONS: The consistent relationships observed between the M235T variant and the protein product and between plasma level of the protein and hypertension status in different ethnic groups provide some evidence for a biochemical mechanism linking DNA variation in the renin-angiotensin system with the hypertension phenotype.

Adult↗
PubMed1997

The angiotensin converting enzyme and blood pressure in Jamaicans.

An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme gene influences the level of serum angiotensin converting enzyme activity and has been associated with risk of several cardiovascular conditions. The relationship to blood pressure remains uncertain, however. We conducted a population-based survey in Kingston, Jamaica, to examine the association between angiotensin converting enzyme genotype, angiotensin converting enzyme serum activity and blood pressure. Serum angiotensin converting enzyme activity was measured and genotyping performed for the I/D polymorphism in 500 community residents. The overall prevalence of the D allele was 59.3%. Angiotensin converting enzyme genotype was not significantly related to blood pressure (P = .16), although it did influence angiotensin-converting enzyme activity, leading to an increase of 35% among individuals with the DD as compared with II genotype. Angiotensin converting enzyme levels were significantly higher in hypertensives as compared with normotensives (P < .05). A modest correlation was observed between blood pressure and angiotensin converting enzyme activity among untreated individuals (r = 0.11; P = .04), although this did not persist in multivariate analysis. A relationship between body mass index and angiotensin converting enzyme activity was identified in both men and women that was independent of genotype. These data demonstrate findings among blacks which are consistent with other studies and suggest a relationship between angiotensin converting enzyme genotype, and serum activity which is influenced by both genetic and environmental factors. The potential role of ACE on blood pressure control in the population remains uncertain.

Adult↗
PubMed1997

Stress and siblings.

A study was undertaken to investigate the stress experienced by healthy siblings of children undergoing hospitalisation for an acute condition. Nineteen children aged between seven and 11 years old, who had had a sibling hospitalised for 24 hours or more for a surgical, medical or traumatic condition were interviewed. The amount of stress experienced by the siblings was quantified using a perceived change scale (PCS). It was found that 77 per cent of the subjects included in the study had experienced stress during the hospitalisation of a sibling. Siblings over the age of seven years, and those who had visited the hospitalised child more than once, had experienced more behavioural changes. Of those who experienced stress, 77 per cent had feelings of sadness during that time.

Adaptation, Psychological↗
PubMed1996

A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans.

BACKGROUND: Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage. Familial and sporadic cases are recognized, and a gene causing familial disease has been mapped to chromosome 7. Hispanic Americans have a higher prevalence of cavernous malformation than do other ethnic groups, raising the possibility that affected persons in this population have inherited the same mutation from a common ancestor. METHODS: We compared the segregation of genetic markers and clinical cases of cavernous malformation in Hispanic-American kindreds with familial disease; we also compared the alleles for markers linked to cavernous malformation in patients with familial and sporadic cases. RESULTS: All kindreds with familial disease showed linkage of cavernous malformation to a short segment of chromosome 7 (odds supporting linkage, 4X10(10).1). Forty-seven affected members of 14 kindreds shared identical alleles for up to 15 markers linked to the cavernous-malformation gene, demonstrating that they had inherited the same mutation from a common ancestor. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. CONCLUSIONS: Virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor.

Adolescent↗
PubMed1996

The role of intra-operative duplex imaging in arterial reconstructions.

BACKGROUND: This study is a cost-benefit analysis of a less invasive method of intra-operative duplex imaging compared with the use of intra-operative angiogram (including C-arm fluoroscopy) in arterial reconstruction. METHODS: From September 1994 to May 1995, 93 intra-operative duplex imaging studies were performed. Duplex scanning results were recorded for carotid endarterectomy (35), iliac balloon angioplasty and stent placement (12), and infra-inguinal bypass (46). Average cost and time were calculated for each type of study. RESULTS: Thirty-four carotid endarterectomy patients (97%) had normal duplex findings. Three (9%) underwent intra-operative angiogram due to abnormal duplex findings and post-operative neurological deficit. In iliac balloon angioplasty and stent placement cases (12), both intra-operative duplex and C-arm post-stent angiography yielded comparable results in both normal (11) and abnormal (1) studies. In infra-inguinal bypass cases (46), 2 had abnormal duplex findings of the native vessels. Average time and cost required to perform intra-operative duplex studies is significantly less than that required for intra-operative angiogram or C-arm studies. CONCLUSION: Compared with traditional intra-operative angiography, the use of intra-operative duplex imaging is less expensive, less invasive, quicker, and equally accurate when used as an adjunct to access surgical results of arterial reconstructions.

Angioplasty, Balloon↗
PubMed1996

Angiotensinogen and blood pressure among blacks: findings from a community survey in Jamaica.

OBJECTIVE: To examine the association between blood pressure, angiotensinogen levels, angiotensin converting enzyme activity and polymorphisms of the angiotensinogen and angiotensin converting enzyme genes in a population-based sample. METHOD: Five hundred participants were recruited in a house-to-house survey of three communities in metropolitan areas of Kingston and St Andrew, in Jamaica. Demographic data, anthropometric and blood pressure measurements were obtained for each participant during a brief clinic visit. Circulating levels of angiotensinogen and angiotensin converting enzyme activity were measured in venous blood samples. Polymorphisms of the angiotensinogen and angiotensin converting enzyme genes were determined. RESULTS: A weak association between angiotensinogen level, angiotensin converting enzyme activity and blood pressure was identified in this population, but substantial joint effect of angiotensin converting enzyme activity and angiotensinogen level on blood pressure was apparent. Variants of the angiotensinogen gene had inconsistent effects on blood pressure and on the risk of hypertension. Angiotensinogen level and angiotensin converting enzyme activity were significantly related to several measures of obesity, including body mass index, waist circumference and skin fold thickness. CONCLUSION: The angiotensinogen and angiotensin converting enzyme genetic variants which were studied appear to have only a modest relationship with blood pressure and associated anthropometric risk factors among blacks.

Adult↗
PubMed1996

Polymorphisms of renin-angiotensin genes among Nigerians, Jamaicans, and African Americans.

Within the context of an international collaborative study of the evolution of hypertension in the black diaspora, we determined the allelic distribution of hypertension candidate genes for the renin-angiotensin system in three populations of African origin. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and the M235T and T174M variants of the angiotensinogen (AGT) gene were examined in individuals from Nigeria, Jamaica, and the United States. Large differences in the prevalence of hypertension were recorded in door-to-door surveys, ranging from 16% in Nigeria to 33% in the United States. The frequency of the D allele was similar in all groups (54%, 59%, and 63% in Nigeria, Jamaica, and the United States, respectively). The 235T allele of the AGT gene was found in 81% of US and Jamaican blacks and 91% of Nigerians; very little variation was seen for the T174M marker. Despite large differences in hypertension rates, genetic variation at the index loci among these groups was modest. Overall, the frequency of the ACE*D allele was only slightly higher than that reported for European and Japanese populations, whereas the AGT 235T allele was twice as common. Compared with blacks in the western hemisphere, Nigerians had a higher frequency of the 235T allele, which is consistent with 25% European admixture in Jamaica and the United States. The results indicate the potential for etiologic heterogeneity in genetic factors related to hypertension across ethnic groups while suggesting that environmental exposures most likely explain the gradient in risk in the comparison among black populations.

Alleles↗
PubMed1995

Endometrial leukocyte subpopulations in women with endometriosis.

The aim of this study was to investigate whether the endometrium of women with endometriosis differs immunologically from the endometrium of normal fertile women. Endometrial biopsies were obtained from 18 normal fertile women who were requesting sterilisation or reversal of sterilisation and 21 infertile women who had laparoscopically diagnosed pelvic endometriosis. The endometrial biopsies were obtained from both groups during the either early, mid or late luteal phase of the menstrual cycle. A panel of 11 monoclonal antibodies and immuno-histochemical techniques were employed to characterise the endometrial stromal leukocytes in frozen sections. Image analysis was used for semi quantitation of leukocytes. In both groups, the number of endometrial granulated lymphocytes (CD56+ CD38+ cells) and macrophages (CD68+ cells) increased significantly between the early and late luteal phase of the menstrual cycle. Compared with fertile controls, women with endometriosis had fewer T-suppressor/cytotoxic (CD8+) cells and endometrial granulated lymphocytes but more T-helper/inducer (CD4+) cells, CD68+ cells and CD16+ cells. None of these differences reached a statistically significant level. This study has shown that the endometrial lymphoid tissue of women with endometriosis does not differ qualitatively or quantitively from that of normal fertile controls. However, functional differences of endometrial leukocytes between the two groups cannot be excluded.

Adult↗