Management of breast cancer. Self referral service is unique.
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Biomedical subjects
Publications and source records attributed to L Morrison.
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Four recombinant inbred (RI) strains, generated from NZB and RF progenitors, were tested on a two-way shuttlebox and their sera were assayed for serological factors. The four RI strains differed with respect to number of null responses and escape time. The strain with the poorest performance displayed the greatest degree of autoimmunity. The avoidance measures were correlated against the autoimmune serological parameters for the four RI strains and the two progenitors. The number of avoidances was negatively correlated with anti-DNA antibody titer, while the number of null responses showed a positive association with immune complex level. Escape time had positive correlations with IgG, IgM-RF, and immune complexes. These findings are consistent with, and extend, our prior reports that avoidance learning is inversely related to the degree of autoimmunity.
The plasmin protease system may have a role in maintaining the patency of renal tubules and in regulating matrix degradation within the glomerulus. Urokinase-plasminogen activator (u-PA) is a serine protease which plays an important part in the regulation of plasmin production from plasminogen. The synthesis of u-PA by cultured human glomerular cells, in particular mesangial cells, is controversial. The present study describes the presence of u-PA in supernatants of pure cultures of human glomerular epithelial cells (EC), cocultures of EC and human mesangial cells (MC) and whole glomeruli, but not within pure cultures of MC. To confirm the synthesis of u-PA mRNA in glomerular EC, cocultures of EC and MC were tested by in situ hybridization with u-PA antisense and sense digoxigenin-labeled RNA probes. Cytoplasmic localization of u-PA mRNA was demonstrated only in the EC, thus confirming the absence of synthesis of u-PA by human mesangial cells in culture.
The purpose of this study was to investigate whether the endometrium of women with unexplained infertility differs in some immunological aspects from the endometrium of normal fertile women. Endometrial biopsies were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II) at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. A panel of 11 monoclonal antibodies was employed to characterize the leukocyte subsets in frozen sections. Semi-quantification was performed with a Quantimet 970 image analyser. Data were analysed using one- and two-way analysis of variance. Compared with fertile controls, women with unexplained infertility had significantly lower numbers of CD8+ (T suppressor/cytotoxic) cells at each post-LH date. In contrast, the number of CD4+ (T helper/inducer) cells was significantly higher in group II. Throughout the luteal phase, infertile women had fewer CD56+ cells than normal fertile controls. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter with the cycle stage but the mean nuclear diameter and axial ratio decreased from LH+7 to LH+13. The differences observed in endometrial leukocytic subpopulations between fertile and infertile women may contribute to unexplained infertility probably by affecting the embryonic maternal dialogue during the implantation and early placentation period.
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The frequency of the 235T and 174M alleles of the angiotensinogen gene, previously reported to be associated with hypertension in Caucasians and Japanese, was compared between 57 hypertensive African Americans and 130 normotensive African Americans sampled as part of a community survey of hypertension in the Chicago area. The frequency of the 235T allele was unrelated to hypertension status (cases, 83%, control subjects, 82%), as was true for the 174M allele. Compared with Caucasians, the frequency of the 235T allele was twice as high in this African American population, while the frequency of the 174M allele was similar. Even higher frequencies of the 235T allele (93%) were noted in a sample of 122 Nigerians. It appears that the 235T allele is very common in populations of West African origin, although we found no evidence that it confers risk of hypertension.
The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J, do not develop an autoimmune condition. To examine the influence of the Y chromosome on behavior, cortical ectopia incidence, and immune functioning, males and females of these two strains were compared. Significant strain differences (for both sexes) were found for behavioral measures including discrimination, spatial and avoidance learning, and activity. For immunological parameters, a sex difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB-Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB-Yaa+s. However, there was also a strain difference for IgG in the females (BXSB-Yaa+ greater). No strain difference was found for the presence of ectopias. However, there was a sex difference across both strains, with males having a higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological differences greater than would be predicted by their known genetic differences. The significant differences between the two female groups suggest that the two strains differ with respect to autosomal genes, in addition to the Y chromosome. The incidence of ectopias is independent of this genetic difference and is influenced by the subject's sex.
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Levels and types of bacterial contamination were compared in enteral feeds prepared and administered in hospital or in the home. Samples of feed administered to children suffering from cystic fibrosis were collected for microbiological analysis immediately after preparation, immediately prior to use (unless administered after preparation) and at the end of feeding. No bacteria were detected in 51 (70%) of the 73 feeds sampled on the hospital ward, and in most of the remaining feeds viable counts were less than 10(1) colony-forming units (cfu) ml-1. However, only four (18%) of the feeds sampled in the home were free from bacterial growth and the remaining 18 feeds contained from 10(1) to more than 10(6) cfu ml-1. Bacteria isolated from feeds sampled both in hospital and the home, included Staphylococcus spp., Bacillus spp., viridans and faecal streptococci, Klebsiella spp. and Enterobacter spp. Enterobacter cloacae was isolated from 11 of the 73 hospital feeds and four of the 22 home feeds. Staphylococcus aureus was isolated from five of the home feeds but from none of the hospital feeds. The higher incidence and numbers of bacteria found in home enteral feeds indicate that further, more detailed studies need to be carried out to find the sources and routes of this contamination and devise methods to minimize the problem.
In order to investigate whether the endometrium of women with unexplained infertility differs immunologically from the endometrium of normal fertile women, a panel of six monoclonal antibodies was used to characterize the presence of the beta 1-integrins or very-late-activation antigens (VLA) in the different endometrial compartments. Precisely timed endometrial biopsies at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II). Frozen sections were labelled using an avidin-biotin peroxidase technique. VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups. VLA-4 was detected in group I but was absent from glandular and surface epithelium of group II. VLA-5 was not present in any of the specimens. VLA-6 was identified primarily in the basement membrane of vessels, glandular and surface epithelium in both patient groups. This study indicates that most beta 1-integrins are present in endometrium throughout the luteal phase of the menstrual cycle. The differences observed between the two groups may contribute to unexplained infertility.
Subinvolution of uteroplacental arteries is a well-recognized cause of hemorrhage in the postpartum period. Although the physiological changes in these arteries during pregnancy are well documented, the sequence of events in normal involution is largely unknown. A recent immunohistochemical study has raised the possibility of an abnormal interaction between maternal uterine cells and fetal trophoblast in subinvolution. An indirect immunoperoxidase technique was used to compare deposition of complement components and immunoglobulin in subinvoluted and normally involuted uteroplacental arteries in 25 cases of postpartum hemorrhage. Deposits of C1q, C3d, C4, and C9 were detected within the walls of normally involuted vessels, whereas deposition of C1q, C3d, and C4 was absent in subinvoluted vessels; C9 was detected only focally. Deposition of immunoglobulins G, A, and M mirrored those described for complement components. The results suggest that immunological factors are necessary for the process of normal involution of uteroplacental arteries and are deficient in subinvoluted vessels.
Pregnant women are more likely to contract malaria than their non-pregnant counterparts. The aim of this study was to develop a simple classification system for the histopathological diagnosis of placental malaria infection applicable to placentas collected in field conditions. The placentas were classified into four groups depending on the presence and distribution of parasites and malaria pigment: active infection, active-chronic infection, past-chronic infection, not infected. The frequency of parasitized placentas (26.4%) was in keeping with the prevalence of placental parasitaemia documented in epidemiological studies. An additional 29.8% placentas showed pigment in fibrin only, indicating past-chronic infection. Chronic placental malaria infection was most common in primigravidae, possibly reflecting ineffective clearance of parasites from the placenta. Seasonal fluctuations between infection categories support progression of placental infection with delayed clearance of pigment from fibrin. The proposed classification system has allowed diagnosis of different categories of placental malaria infection by two independent observers. A standardized method of diagnosis may enhance understanding of placental pathology and reduced birth weight in malaria infection during pregnancy.
Malaria in pregnancy is associated with reduced birth weight. Most pathological studies of placental malaria infection have focused on severe Plasmodium falciparum infection. In the present study of 121 placentas delivered in a rural area of The Gambia, malaria infection was diagnosed in tissue sections using a simple classification system and severity of pathology was ranked semiquantitatively. Deposition of malaria pigment in circulating cells was associated with active infections whereas pigment in fibrin was a feature of active-chronic infections. Primigravidae had higher levels of pigment at all sites, although these observations were not always significant. Thickening of the trophoblast basement membrane occurred in all infection categories but fibrinoid necrosis of chorionic villi was a feature of active and active-chronic infection. Both birth weight and placental weight were increased in infected placentas but widespread trophoblast basement membrane thickening was associated with decreased birth weight. Both birth weight and placental weight decreased with increased fibrinoid necrosis and cytotrophoblast prominence but the results were not significant. By this approach it has been possible to correlate placental pathology with different infection categories and to analyse the pathological features associated with decreased birth weight.
We report a 38-year-old nurse who developed amyotrophic lateral sclerosis (ALS) beginning in September 1990. In May 1991, her 38-year-old husband developed dysarthria, which progressed to typical ALS. This is the fourth report in the literature of conjugal ALS occurring outside of Guam. Although this event is most likely due to coincidence, exogenous agents should be considered in the etiology of ALS.
In a previous study, in which fertilized DBA ova were transferred into an autoimmune female, and NZB ova were transferred into a non-autoimmune female, we found that (1) the maternal environment affected the degree of autoimmunity, (2) the incidence of cortical ectopias was not affected by the maternal environment (3) DBA and NZB females had greater paw asymmetry if reared in an autoimmune uterus, and (4) avoidance learning scores were inversely related to degree of autoimmunity. In the present experiment, reciprocal crosses of DBA and BXSB mice were studied to confirm and extend the original findings. DB mice (DBA female x BXSB male) had greater immune activity than the BD animals, had poorer avoidance learning, but were better on black-white discrimination learning and the Lashley III maze. The BD mice had greater paw asymmetry. Only one of 38 animals had a cortical ectopia. The results lead to the following conclusions: (1) there is an inverse relationship between amount of immune activity and active avoidance learning; (2) some uterine factor in autoimmune mice causes females to have greater paw asymmetry; (3) cortical ectopias are under genetic control; and (4) the lesser immune activity of the BD mice suggests that they developed a suppressor system following early exposure to autoimmunity in the uterine/maternal environment.
Interest in immunoregulatory mechanisms within uteroplacental tissues, particularly in malarial infection during pregnancy, prompted us to develop a technique to extract maternal mononuclear cells from human term placentas. This method is described. The phenotypes of isolated cells were characterised for expression of CD45, CD3, CD4, CD8, CD14, CD15, CD68, CD22, CAM 5.2 and class II MHC antigens and compared with those in situ in frozen sections of the same placentas. Isolated mononuclear cell preparations were examined for contamination by fetal trophoblasts. Fetal leukocyte contamination appeared unlikely since histological sections of placental tissue, after the extraction of maternal leukocytes, showed intact chorionic villi with no disruption of fetal stem vessels. This technique produces preparations of maternal placental mononuclear cells which are representative of cells in situ, show minimal fetal cell contamination and are suitable for functional studies.
1. An ambulatory activity monitor with solid-state memory was employed to obtain 24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9 normal controls. 2. The activity monitor is a piezoelectric device which was strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of akathisia and lower levels of daytime activity. 4. Manic and depressed patients showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement of activity may be complicated by the patient's psychiatric disorder.