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Biomedical subjects

C A Foster

Publications and source records attributed to C A Foster.

At least 37 records · Page 2Linked to original sources
PubMed1992

Human monoclonal antibody recognizing an antigen associated with ovarian and other adenocarcinomas.

MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian cancer, has been used to study the distribution and characteristics of its target antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41 epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas. Among normal tissues the MS2B6 antigen was found in the adult epithelia of the fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and large renal ducts. No detectable antigen was found in peritoneal epithelia, tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60 kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6 antigen is located in a layer of the peripheral cytoplasm beginning just below the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.

Adenocarcinoma↗
PubMed1992

ICAM-1 expression in a spontaneously transformed human keratinocyte cell line: characterization by a simple cell-ELISA assay.

Interferon gamma (IFN-gamma) is known to induce ICAM-1 on keratinocytes (KC) in vitro, and its expression in vivo is correlated with epidermal T-cell infiltration in various dermatoses. However, the mechanisms for this cytokine-mediated ICAM-1 expression are essentially unknown. We investigated the induction of ICAM-1 by IFN-gamma in HaCaT cells, a spontaneously transformed human KC cell line, using an immunoperoxidase-ELISA with the monoclonal antibody (MoAb) R6.5. HaCaT cells constitutively expressed low levels of ICAM-1, which were upregulated by IFN-gamma. The kinetics and dose response were similar to those published for primary KC, regardless of whether the HaCaT cells were cultured in low- or high-calcium medium. ICAM-1 expression was increased significantly at 4 h with 500 U/ml IFN-gamma, and reached a plateau (approximately 5 x greater than constitutive) by 24 h. At concentrations greater than 10 U/ml for 24 h, IFN-gamma induced ICAM-1 expression in a dose-dependent fashion (half maximal at 100 U/ml). TNF-alpha alone, and in synergistic combination with IFN-gamma, also upregulated the expression of HaCaT ICAM-1. IFN-gamma treatment of HaCaT cells increased the level of ICAM-1 mRNA and enhanced (approximately 3x) the adherence of fluorescently labeled (calcein) human T lymphoblasts, as determined by Northern blotting and an in vitro adhesion assay, respectively. Our findings suggest that HaCaT cells, in conjunction with a simple immunoperoxidase cell-ELISA, provide a reliable system for studying pharmacologic modulation of ICAM-1 on KC.

Blotting, Northern↗
PubMed1992

Isolation of human immunodeficiency virus type 1 from human epidermis: virus replication and transmission studies.

For a better understanding of the pathogenetic events operative in the cutaneous manifestations of human immunodeficiency virus type 1 (HIV-1) disease, we investigated whether epidermal cells (EC) from HIV-1-seronegative persons can be infected with HIV-1 and, vice versa, whether HIV-1 can be rescued from the epidermis of HIV-1-infected individuals. In a series of three experiments, we consistently found that exposure of EC from HIV-1-seronegative donors to HIV-1 led to viral replication in these cells as evidenced by the detection of HIV-1 p24 in culture fluids. Because EC had been substantially enriched for Langerhans cells (LC) before being exposed to HIV-1, it is reasonable to assume that these CD1a+/CD4+/MHC class II+ antigen-presenting cells of the epidermis represented the actual targets of infection. This assumption is further strengthened by the observation that T cell-depleted cell suspensions from Langerhans cell histiocytosis (LCH) lesions could be productively infected with HIV-1. Conversely, co-culture of epidermal sheets from HIV-1-seropositive individuals with mononuclear phagocytes (MNP) from HIV-1-seronegative donors resulted, after 3 to 5 weeks, in the detection of HIV-1 p24 in 12 of 23 cases. Immunocytochemical analysis, using a monoclonal antibody specific for p24, revealed the presence of HIV-1 in adherent MNP in three cocultures tested. In addition, cellular DNA from these cultures showed strong signals when hybridized to a HIV-1-specific DNA probe. The further finding that two isolates examined exhibited different restriction enzyme patterns indicates that they are separate entities rather than contaminants. Transmission of these isolates to MNP, B- or T-cell lines resulted in cultures strongly positive for p24 and, in the case of H9 cells, for viral particles as detected by electron microscopy. Our results therefore strongly suggest that EC not only can serve as targets for HIV-1, but also can allow efficient virus replication and transmit HIV-1 to various cell types of the hematopoietic lineage.

Cell Line↗
PubMed1991

First clinical study of the selective 5-HT3 antagonist, granisetron (BRL 43694), in the acute treatment of migraine headache.

Granisetron (BRL 43694), a selective 5-HT3 receptor antagonist, was assessed as acute therapy for the first time in migraine patients. In an open pilot study 7 migraine attacks were treated in 6 patients. All but 1 patient experienced marked and rapid relief from the headache, and nausea and vomiting were rapidly resolved in the 6 cases where these symptoms accompanied the attack. No side effects were recorded. Development of granisetron for migraine was suspended during the study for extraneous reasons.

Adult↗
PubMed1990

Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor.

The epidermis of clinically normal-appearing human skin harbors a phenotypically heterogeneous population of T lymphocytes (TCs), the majority of which are CD2+/CD3+/CD5+ "memory" cells, but in an unactivated state, and express the TCR-alpha/beta. In contrast to murine skin, only a very minor subpopulation of CD3+ cells in the human epidermis bears the TCR-gamma/delta. Epidermal TCs primarily are distributed along the rete ridges in the basal keratinocyte layer and are often in close apposition to Langerhans cells (LCs). These TCs were propagated from epidermal cell suspensions after stimulation with TC activating agents (Con A, rIL-1, rIL-2), then evaluated for phenotypic features and TCR diversity. Similar to the in situ situation, most were CD4-/CD8+/TCR-alpha/beta+. In addition, two cultures contained TCR-gamma/delta+ cells; one of these determined to be an adherent CD4-/CD8+ population. Epidermal TCs were significantly (p less than 0.0001) more abundant in the sole than in the other body regions examined (i.e., 40 vs. 7 CD3+ cells/linear centimeter of epidermis) and seemed to have a particular affinity for the acrosyringial epithelium of eccrine sweat ducts. Moreover, the sole usually contained a greater number of CD8+ relative to CD4+ TCs, whereas the epidermal CD4/CD8 ratio in the trunk and extremities was quite variable, although the trend also was towards a slightly larger percentage of CD8+ cells. Collectively, our data suggest that the volar epidermis has a unique microenvironment which is responsible for both the higher density of TCs, preferentially CD8+, and lower number of LCs. This study has not only provided evidence for significant regional variability in the human epidermal TC population of normal skin, but also strengthens the concept for skin-associated lymphoid tissues (SALT), whereby memory TCs recirculate back to the epidermis and interact with resident antigen-presenting cells (i.e., LC).

Antibodies, Monoclonal↗
PubMed1989

Ontogeny of Langerhans cells in human embryonic and fetal skin: cell densities and phenotypic expression relative to epidermal growth.

Langerhans cells (LCs) positive for HLA-DR antigens were present in developing human epidermis by at least 7 weeks estimated gestational age (EGA). Most were negative for CD1 (T6) until 12-13 weeks EGA when they underwent a dramatic increase in CD1 reactivity. To gain insight into the density of LCs during ontogeny and to assess whether their distribution was coordinated with epidermal growth, the number of cells positive for both HLA-DR and CD1 antigens was determined relative to surface area and to volume of developing, interfollicular epidermis. LCs differed in their phenotype, distribution (follicular vs. interfollicular), size, and shape between 7 and 21 weeks EGA; however, during this period they maintained a statistically equivalent (P greater than .25) density (65 cells/mm2 and 1,750/mm3) even though the epidermis increased in thickness and the fetus rapidly expanded its surface area. While LCs were evenly distributed within the epidermal sheets at all gestational ages, those in embryonic skin were much smaller and less dendritic than the older cells. The density, size, and shape of LCs in developing skin seemed to be independent of epidermal status (e.g., thickness of keratinization, and number of cell layers) but rather were correlated with gestational age. The number of fetal LCs, through at least 23 weeks EGA, was only 10-20% of the adult LC density. Thus, we can conclude that the increase in LC density to adult levels must occur either during the third trimester or after birth.

Cell Aggregation↗
PubMed1988

Heterosexual spread of human immunodeficiency virus in Edinburgh.

Heterosexual transmission of human immunodeficiency virus (HIV) was investigated in 123 subjects with no apparent risk factor for infection other than having had heterosexual intercourse with a person who was either infected with HIV or at high risk of being infected with it. Seven subjects were found to be infected with the virus. Risk factors for transmission included being the regular sexual partner of an abuser of intravenous drugs and having a sexual relationship of more than 18 months' duration. Anal intercourse was not a risk factor in the three subjects who admitted to it. There were 41 regular partnerships with abusers of intravenous drugs in which the antibody state and history were fully known for both partners. In these partnerships male to female transmission of the virus occurred in five out of 34 (15%) and female to male in one out of seven. In 30 couples in whom one partner was known to be positive for HIV and an abuser of intravenous drugs four female partners were found to be seropositive at first testing, but there were no new positive results on subsequent serial testing. In six of these 30 couples both partners abused intravenous drugs but the partner who was negative for HIV remained so. Few of the partnerships always practised safe sexual techniques, even after a partner was known to be positive for HIV. Heterosexual transmission of HIV occurred but was incomplete and may be related to the timing of the relationship with the infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Repair of nasal septal perforation utilizing the midface degloving technique.

A technique utilizing the midfacial degloving approach in the repair of nasal septal perforations in 24 patients is reported. The midface degloving approach was limited to patients with septal perforations greater than 3 cm and failed prior attempts at surgical closure. Bilateral posteriorly based unipedicled flaps were utilized in the septal closure. Complete closure was accomplished in 75% (18/24) of cases, with a follow-up of one to three years. Complications included reperforation in 25% (6/24) of cases and partial vestibular stenosis in 20% (5/24) of cases. A modification of our technique, relining the nasal floor with postauricular full-thickness skin grafts, has alleviated vestibular stenosis.

Evaluation Studies as Topic↗
PubMed1988

Morphometric and statistical analyses describing the in utero growth of human epidermis.

Epidermal development of human embryonic and fetal skin from the lower limb was studied using morphometric and statistical methods. Epidermal growth, as defined by an increase in epidermal thickness and the number of cell layers, occurred in three distinct stages during the first and second trimesters. The first growth spurt occurred between 5 and 13 weeks estimated gestational age (EGA) and was followed by a plateau phase with little change in epidermal thickness from 14 to 21 weeks, after which the epidermis began to increase in height again. The periderm reached its maximal height by approximately 13 weeks EGA, and by 25 weeks was shed into the amniotic fluid. Thus, within a five-month period (5 to 25 weeks EGA) the epidermis changed from a single cell layer less than 10 micron thick to a 10 to 12-cell layer, keratinized epithelium greater than 60 micron thick. In contrast, epidermis from adult lower limb consisted of about 25 cell layers and was almost 75 micron in thickness. The age-related differences in epidermal thickness probably reflect changes in cell size and shape more than changes in the directional movement (apically vs. laterally) of proliferating keratinocytes, because the addition of cell layers throughout development was relatively constant. During the plateau phase, when there is a rapid increase in fetal growth rate, the suprabasal keratinocytes become more flattened, thereby allowing for the addition of new cell layers while maintaining a relatively constant epidermal thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryonic and Fetal Development↗
PubMed1987

Differential effects of tissue processing on human embryonic and fetal skin.

To most accurately evaluate quantitative data from studies of developing epidermis, the effects of tissue processing on human embryonic and fetal skin (8-20 weeks gestational age) were examined using two different techniques: 1) EDTA-separated epidermal sheets that were briefly fixed in 2% paraformaldehyde, processed through Permount infiltration, and prepared as whole mounts on glass slides, and 2) skin that was fixed in Karnovsky's fixative and embedded in Epon. Based on en face measurements of surface area before and after tissue processing, both procedures caused differential, age-dependent shrinkage. However, the trend of increasing shrinkage was inversely related to increasing age in the paraformaldehyde-fixed epidermal sheets (y = 57.14 + 1.26x, where x = gestational age in weeks and y = % of original surface area), but directly correlated with aging in the Karnovsky-fixed skin (y = 955.62 - 232.77x + 20.38x2). Shrinkage of epidermal sheets occurred during the dehydration and clearing steps, whereas most of the dimensional changes in whole skin took place during fixation in Karnovsky's. These differences are probably due to greater cross-linking of proteins and longer fixation time in the more concentrated and fast-acting Karnovsky's, as well as the influence of increasing quantities of fibrous proteins in the dermis of whole skin.

Epidermal Cells↗
PubMed1987

Prevention of developmental disabilities: a model for organizing clinical activities.

Prevention of developmental disabilities receives widespread support, however, a comprehensive approach involving federal and local governments, major professional groups, and the general public has yet to be defined and implemented. Three major issues appear to impede a coordinated approach: (a) prevention's image problem; (b) the complexity surrounding prevention efforts; and (c) the absence of consistent evaluation methods. The University of California, Irvine-University Affiliated Program has developed a model for prevention activities in response to these issues. This model is interdisciplinary, promotes reasoned cooperative efforts, and provides a basis for evaluation and research. This paradigm can be helpful to policy makers in prioritizing prevention activities. The model is composed of five major and functional approaches to prevention with a central core devoted to ethical considerations. The model emphasizes the variety, scope and interdisciplinary nature of prevention/intervention activities, as well as the necessity for a longitudinal approach.

Attitude↗
PubMed1986

Ontogeny of Langerhans cells in human embryonic and fetal skin: expression of HLA-DR and OKT-6 determinants.

Langerhans cells (LCs) have been identified in human skin by 10 weeks estimated gestational age (EGA), but it was not known when they first enter the epidermis or acquire HLA-DR, OKT-6, and ATPase reactivity. We assayed for LCs in human embryonic and fetal skin by using immunolabeling and histochemical techniques on epidermal sheets. HLA-DR+ and ATPase+ LCs were present in the epidermis by 6-7 weeks EGA, the youngest tissue examined. Most LCs were OKT-6- until about 12 weeks EGA when they underwent a dramatic increase in OKT-6 reactivity. Although LC densities between 50-100 days were statistically similar (100 cells/mm2 of epidermis), LCs early in development were smaller, less dendritic, and phenotypically heterogeneous. We conclude that LCs migrate into the epidermis during the first trimester and resemble the adult phenotype by the second trimester, long before the immune system is fully activated.

Adenosine Triphosphatases↗
PubMed1983

Propranolol-epinephrine interaction: a potential disaster.

Presented here are six examples of potentially life-threatening propranolol-epinephrine interactions. The only report found that warns of a deleterious clinical interaction between propranolol and epinephrine appeared in 1980. With widespread use of propranolol for approved and unapproved conditions, the population at risk is significant. All physicians and dentists using local anesthetic with epinephrine should be aware of this interaction.

Autonomic Nervous System↗
PubMed1982

Chronic osteomyelitis following mandibular fractures and its treatment.

In a review of 350 patients with mandibular fractures between 1976 and 1978, eight cases of chronic mandibular osteomyelitis were found. Treatment in all cases consisted of intravenous antibiotics and debridement. In addition, in some cases a suction-irrigation system was used after debridement. From this study, the following can be stated: (1) Osteomyelitis following mandibular fractures is uncommon. (2) Once chronic osteomyelitis has developed, aggressive antibiotic and surgical treatment is needed. (3) The use of the suction-irrigation system after debridement is an effective adjunctive aid in treating osteomyelitis. Cosmesis is superior to that obtained with older techniques because wounds are closed primarily.

Adult↗
PubMed1982

Stomach cancer following gastric surgery for benign disease.

The records of 1,079 patients with gastric carcinoma were reviewed. Of these, only 21 (about 2%) had had previous gastric surgery for benign disease, usually peptic ulcer. The average interval between the original gastric surgery and the discovery of stomach cancer was 26.9 years. The symptoms of cancer presentation were not distinguishable from other forms of the postgastrectomy syndrome. Gastric cancer tended to develop in these patients during the sixth decade of life, irrespective of when they had had their original gastric surgery, strongly suggesting an age-related factor. Although it would appear that previous gastric surgery for benign disease is not a major risk factor for the subsequent development of gastric cancer, such a relationship may exist. Patients who have undergone gastrectomy should be followed up carefully for the recurrence of symptoms.

Adenocarcinoma↗