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Biomedical subjects

A King

Publications and source records attributed to A King.

At least 271 records · Page 15Linked to original sources
PubMed1994

Expression of c-kit and kit ligand at the human maternofetal interface.

Kit ligand, or stem cell factor, is a recently identified growth factor, which binds to and activates the c-kit proto-oncogene, and which has been shown to act synergistically with other haematopoietic growth factors in the bone marrow. We have previously shown that several isoforms of kit ligand, which arise due to alternative splicing, are expressed in human placenta. In order to elucidate the role of c-kit and its ligand during human placental development we have investigated the expression of c-kit and kit ligand in human first trimester and term placenta as well as in pregnant and non-pregnant endometrium, by immunocytochemistry and flow cytometric analysis. In non-pregnant endometrium no expression of kit ligand was seen. By contrast, in first trimester decidua, kit ligand was strongly expressed by the arterial media of maternal blood vessels. Kit ligand was also expressed throughout pregnancy by invasive fetal extravillous trophoblast, and by fetal fibroblasts within the placental villi. c-kit was found to be expressed on Hofbauer cells within the chorionic villi, and by decidual macrophages at all stages in pregnancy. c-kit was also detected on the small CD56dim subset of uterine large granular lymphocytes which form the major leukocyte population in human first trimester decidua. Our results suggest that kit ligand may be involved in the regulation of fetal macrophages, and in particular in signalling between invading extravillous trophoblast which expresses kit ligand, and maternal leukocytes bearing the c-kit receptor.

Amino Acid Sequence↗
PubMed1994

Reciprocal expression of epidermal growth factor receptor (EGF-R) and c-erbB2 by non-invasive and invasive human trophoblast populations.

Trophoblast invasion of the maternal uterus during human placentation is a highly complex process involving proliferation, migration and cell differentiation. Tyrosine kinase receptors are known to be involved in such functions. The epidermal growth factor-receptor (EGF-R) and c-erbB2 proto-oncogene products are two closely related tyrosine kinase receptors which are expressed in high amounts in human placenta. In this study, we have investigated the expression of EGF-R and c-erbB2 proteins by different trophoblast populations using immunohistochemistry. EGF-R was expressed by proliferative villous cytotrophoblasts, but not by non-proliferative, invasive, extravillous cytotrophoblasts. In contrast, c-erbB2 was expressed by invasive extravillous trophoblasts (EVT) but not by villous cytotrophoblasts. Expression of both receptors was seen only by the terminally differentiated placental bed giant cell and villous syncytiotrophoblast populations. This precise spatial expression suggests that EGF-R plays an important role in trophoblast proliferation whereas c-erbB2 may be important for trophoblast invasion and differentiation. The surface expression of these receptors on normal isolated first trimester trophoblasts and on choriocarcinoma cell lines was also investigated by flow cytometry, and compared with that of the c-erbB2-overexpressing mammary tumour cell line BT474. Isolated trophoblasts were shown not to overexpress c-erbB2, and no differences in either EGF-R or c-erbB2 expression were seen between normal and malignant trophoblasts.

Breast Neoplasms↗
PubMed1994

Human papillomavirus gene sequences in washed human sperm deoxyribonucleic acid.

The present study demonstrated the presence of HPV gene sequences in Percoll-washed sperm cells using polymerase chain reaction primers targeting smaller gene regions. Up to 64% of the sperm specimens were shown to contain gene sequences indicative of the presence of HPV. Human papillomavirus type 16 was detected about twice as often as HPV type 18. The results suggest the possible role of sperm as a vector for HPV.

DNA, Viral↗
PubMed1994

Expression of adhesion molecules by endovascular trophoblast and decidual endothelial cells: implications for vascular invasion during implantation.

During the process of implantation, maternal spiral arteries within the decidua are invaded by trophoblast cells that adhere to and migrate along the luminal surface of the vascular endothelial cells. This phenomenon resembles the events that occur during the migration of neutrophils into an acute inflammatory site, therefore it is possible that similar mechanisms are involved. Indeed, previous observations have shown that endovascular trophoblast expresses the blood group-related antigen sialyl Le(x). In this study, we show, by immunohistology, the expression of both E- and P-selectin by vascular endothelial cells only in the decidua basalis and not in decidua parietalis. In contrast, ICAM-1 is expressed by all vascular endothelium throughout the decidua. Expression of VCAM-1 is variable at the implantation site, and is not expressed by vascular endothelial cells in decidua parietalis. Interestingly, we demonstrate the strong expression of a polysialylated form of NCAM by endovascular trophoblast. Our data suggests that vascular invasion by trophoblast is regulated by the expression of appropriate adhesion molecules which permit interaction between endovascular trophoblast and decidual endothelial cells.

Cell Adhesion Molecules↗
PubMed1994

Production of granulocyte-macrophage colony-stimulating factor by human trophoblast cells and by decidual large granular lymphocytes.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has been implicated in placental growth and development. In this study, we investigated the production of GM-CSF in human first trimester pregnancy by the predominant uterine lymphocyte population of decidual CD56+ NK cells (large granular lymphocytes) and the factors that influence this production using enzyme-linked immunosorbent assays (ELISAs) and bioassays, supplemented by immunocytochemistry. We have also investigated and compared production of GM-CSF by human first trimester trophoblast and by JEG-3 and JAR choriocarcinoma cells. Our data show that appreciable amounts of GM-CSF are produced in first trimester maternal decidua and that a significant component of this secretion was from decidual large granular lymphocytes (LGL). Production of GM-CSF by LGL was constitutive and considerably greater than that of freshly isolated peripheral blood leukocytes. GM-CSF secretion by decidual LGL could be enhanced by co-culture on a monolayer of decidual stromal cells, and could also be increased in a dose-dependent manner by stimulation with interleukin-1 (IL-1) or IL-2. IL-4, IL-6, tumour necrosis factor alpha (TNF alpha), transforming growth factor beta (TGF beta), interferon alpha (IFN alpha) and IFN gamma individually had no effect on GM-CSF secretion, although IL-4, TGF beta and IFN alpha all inhibited the action of IL-2. IFN gamma had no effect on the IL-2-induced GM-CSF secretion, but did antagonize the action of IL-1. Normal human first trimester trophoblast was also found to produce GM-CSF, although no production whatsoever was seen by JEG-3 or JAR choriocarcinoma cells. These results suggest that GM-CSF from uterine lymphocytes, and from trophoblast itself, may influence placental growth and development in both a paracrine and an autocrine manner.

Antigens, CD↗
PubMed1994

Evaluation of tuberculin reactivity in BCG-immunized siblings.

The purpose of the present study was to determine in BCG-immunized sibships < or = 14 yr of age whether the correlations of intensity of tuberculin reactivity support a genetic regulation of the response to BCG immunization. The study population consisted of 659 healthy children living in 265 households exposed to an adult with tuberculosis: 38 children did not have a BCG scar, 327 children had one BCG scar, and 294 had two BCG scars from vaccinations at birth and at 6 yr of age. There were 603 full siblings, 16 half-siblings, and 40 unrelated children. Tuberculin testing was performed by one trained nurse. Sibling correlations of the intensity of the tuberculin response were calculated after adjusting for various nongenetic covariates that could be important in predicting it. The sibling correlations were significant at the 1% significance level. There was no significant correlation of tuberculin reactivity among unrelated children in the same household. These results are consistent with genetic regulation of the development and persistence of tuberculin reactivity after BCG immunization.

Adolescent↗
PubMed1994

Gastric cell phenotypes and intestinal metaplasia in Polynesian and non-Polynesian residents of New Zealand.

Previous studies have indicated that the frequency of different cell phenotypes as well as of the mucosal extension of intestinal metaplasia (IM) in the gastric mucosa varies in different geographic regions (Scandinavia, Japan, Mexico, Hawaii, and mainland U.S.A.). These variations appear to be influenced by environmental factors but not by the race of the individuals. In the present work, 241 gastrectomy specimens from the two main racial groups in New Zealand, indigenous Pacific Island Polynesians (mainly Maoris) and non-Polynesian settlers (mainly of European ancestry), were examined. The occurrence of histologic changes known to be influenced by the environment such as intramucosal gastric cysts, intestinal metaplasia (IM), ciliated metaplastic cells, and cells with large vacuoles were recorded. The mucosal extension of IM was classified into low IM (having one to five areas with IM in at least one of the sections) and high IM (having one area with IM in all microscopic fields in at least one of the sections or occupying entire fields in one or more sections). Polynesians with adenocarcinomas and peptic ulcers were younger than non-Polynesians. The gastric mucosa in younger Polynesians harboring an intestinal type carcinoma or a peptic ulcer differed from that of non-Polynesians; Polynesians more often had intramucosal cysts, high IM scores, or ciliated metaplastic cells at a younger age than non-Polynesians. These results suggest that the gastric mucosa of Polynesians may be exposed to environmental factors (ulcerogenic or carcinogenic) at an earlier age than the gastric mucosa of non-Polynesians in New Zealand.

Adult↗
PubMed1994

Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis.

It has been proposed that renal tubular damage and chronic hydrocarbon exposure are causally related to progression of renal failure in primary glomerulonephritis. We examined the relationship between hydrocarbon exposure and morphological parameters of tubulointerstitial damage in 59 patients with biopsy-proven primary glomerulonephritis (proliferative, n = 52; membranous, n = 7). From a mean follow-up period of 6 years patients were divided into two groups (GP) according to the presence or absence of progressive renal failure (GP 1, n = 24 with progressive renal failure) and (GP 2, n = 35 without progressive renal failure). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood-pressure control. Patients were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Biopsy cylinders were blindly assessed retrospectively for relative interstitial volume of the renal cortex by the point-counting method. In addition an assessment was made of the degree of fibrosis and chronic inflammatory cellular infiltrate. Hydrocarbon exposure score derived from the questionnaire until the time of renal biopsy correlated both with interstitial volume (r = 0.55; P < 0.001) and serum creatinine (r = 0.46; P < 0.001). Moreover, interstitial volume also correlated with serum creatinine (r = 0.63; P < 0.001). Chronic hydrocarbon exposure scores and relative interstitial volume in the renal cortex at the time of renal biopsy was significantly higher in GP 1 than GP 2 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Detection and significance of pulmonary Hodgkin's disease at autologous bone marrow transplantation.

Pulmonary Hodgkin's disease (HD) is considered to carry a poor prognosis both at presentation and at relapse. We have therefore studied the incidence and significance of pulmonary involvement in 190 poor risk HD patients undergoing BEAM therapy and ABMT for relapsed or resistant disease. Forty-one of 190 patients (22%) had clinically diagnosed pulmonary HD at some stage of their disease prior to ABMT. In 29 patients, in whom a full set of CT scans was available, the patterns of pulmonary HD were characterised. Four of 29 patients had pulmonary disease at presentation only, 8 of 29 at presentation and ABMT and 17 of 29 developed pulmonary involvement at relapse and proceeded to ABMT with persistent pulmonary disease. The commonest pulmonary abnormalities at presentation and relapse were discrete nodules (72%), masses extending from hilar or mediastinal nodes (34%) and pleural effusion/thickening (28%); 52% had two or more patterns of involvement and 66% had coexistent mediastinal lymphadenopathy. There was no relationship between pattern or bulk of pulmonary involvement and outcome. Consideration of the outcome following ABMT in all 190 patients revealed no significant difference in progression-free survival at 5 years between the pulmonary HD group (43%) and those without lung involvement (48%). Furthermore, there was no significant difference in complete remission or transplant-related death rates between the two groups. This would suggest that pulmonary involvement is not in itself a contraindication to ABMT and some patients with bulky pulmonary disease are capable of long-term survival.

Adult↗
PubMed1994

Cochlear dysplasia and meningitis.

Congenital dysplasias of the labyrinth of the inner ear are associated with varying degrees of hearing loss. There is a risk of a fistulous communication between the subarachnoid space and the middle ear cavity in some cases that present either as cerebrospinal fluid otorhinorrhea or as recurrent attacks of meningitis. The types of deformity where such a fistula is likely have not been clearly defined. The authors correlated the hearing state with the imaging assessment in 20 patients with congenital malformation of the labyrinth and, in particular, the cochlea. In addition the postmortem histologic findings from one patient with severe cochlear dysplasia who died from otogenic meningitis are described. The key to the assessment is the basal turn of the cochlea. If the basal turn is present and of normal caliber then some hearing is possible and there is no risk of a major fistula. However, if the basal turn is wider than normal or replaced by an undeveloped sac then there is anacusis and very real risk of fistula. In such cases the deformed labyrinth needs to be packed with fibrofatty tissues after just one attack of meningitis.

Adolescent↗
PubMed1993

Structure of a major immunogenic site on foot-and-mouth disease virus.

Attachment of foot-and-mouth disease virus (FMDV) to its cellular receptor involves a long and highly antigenic loop containing the conserved sequence, Arg-Gly-Asp, a motif known to be a recognition element in many integrin-dependent cell adhesion processes. In our original crystal structure of FMDV the Arg-Gly-Asp-containing loop ('the loop'), located between beta-strands G and H of capsid protein VP1, was disordered and hence essentially invisible. We previously surmised that its disorder is enhanced by a disulphide bond linking the base of the loop (Cys 134) to Cys 130 of VP2 (ref. 8). We report here the crystal structure of the virus in which this disulphide is reduced. Reduced virus retains infectivity and serological experiments suggest that some of the loop's internal structure is conserved. But here its structure has become sufficiently ordered to allow us to describe an unambiguous conformation, which we relate to some key biological properties of the virus.

Aphthovirus↗
PubMed1993

Expression of adhesion molecules by human decidual large granular lymphocytes.

This study has examined the expression of adhesion molecules by uterine-specific CD56bright CD16-CD3- large granular lymphocytes using flow cytometry and immunohistology. Data are compared with those obtained after IL-2 stimulation and with peripheral blood CD56+ cells. We have found that decidual CD56bright cells strongly express three fibronectin receptors, alpha 4 beta 1, alpha 5 beta 1, and alpha 4 beta 7. The HML-1 antigen is also expressed. The beta 2 integrins are also found on decidual CD56+ cells although, apart from CD11c, these are present at levels lower than those of corresponding cells in blood. After IL-2 stimulation there is a considerable increase in CD11a/CD18 expression on CD56bright cells. Both ICAM-1 and NCAM are found on CD56bright cells at higher levels compared to those of peripheral blood CD56+ cells. This pattern of expression of beta 1 and beta 2 integrins and members of the immunoglobulin superfamily must have important implications in the behaviour of decidual LGL. These adhesion molecules are also likely to be important in the recruitment and retention of CD56bright LGL in the decidual microenvironment particularly as the specialised decidual extracellular matrix and uterine LGL appear concomitantly at the time of implantation.

Antigens, CD↗
PubMed1993

Malignant teratoma arising in a dysgenetic gonad.

A case of malignant teratoma arising within a dysgenetic gonad in a 21-year-old phenotypic female with a 46 XY karyotype is presented. Admixtures of dysgerminoma, yolk sac tumor in close juxtaposition to embryoid bodies and elements of choriocarcinoma were also present. The contralateral gonad was an unidentifiable fibrovascular streak. Neither gonadoblastoma nor coarse calcifications (such as commonly found in gonadoblastoma) could be identified. We believe that the present case arose de novo in a dysgenetic gonad and, uncharacteristically, was not associated with a gonadoblastoma.

Adnexa Uteri↗
PubMed1993

Effect of IFN-gamma and IFN-alpha on killing of human trophoblast by decidual LAK cells.

Human decidual large granular lymphocytes are capable of killing both normal trophoblast and choriocarcinoma cells after stimulation with recombinant interleukin-2 (rIL-2) in vitro. We now show that pre-treatment of normal trophoblast and JEG-3 choriocarcinoma cells with interferon-gamma (IFN-gamma) protects these target cells from killing by decidual effectors, although pre-treatment with interferon-alpha (IFN-alpha) had no such effect. In contrast, JAR choriocarcinoma cells were readily killed before and after exposure to both IFN-gamma and IFN-alpha. This protective effect might be due to upregulation of non-classical trophoblast HLA Class I molecules, as IFN-gamma but not IFN-alpha enhances Class I surface expression in both normal trophoblast and JEG-3 choriocarcinoma cells. JAR cells, however, are constitutively and inductively negative for Class I expression.

Cell Death↗