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Biomedical subjects

R Ford

Publications and source records attributed to R Ford.

At least 91 records · Page 5Linked to original sources
PubMed1994

Normal colonic epithelium adheres to carcinoembryonic antigen and type IV collagen.

BACKGROUND/AIMS: Human colorectal carcinoma cells bind to collagen and laminin in the basement membrane as well as to carcinoembryonic antigen (CEA) on neighboring cells. The purpose of this study was to determine whether normal colonic epithelial cells bind to CEA, collagen, or laminin. METHODS: Intact colonic crypts were isolated from normal mucosa in 13 specimens resected for colorectal carcinoma or colonic diverticulitis. Colonocytes were released from the crypts by treatment with collagenase and deoxyribonuclease and tested for adhesion to CEA, type IV collagen, and laminin in a solid-phase adhesion assay. RESULTS: Twelve percent to 25% of colonocytes in all specimens bound to CEA. Colonocytes from seven specimens also bound to type IV collagen, but none of the colonocyte preparations bound significantly to laminin. Monoclonal antibodies to CEA and to the hyaluronate receptor CD44 and enzymatic removal of membrane CEA blocked the adhesion of colonocytes to CEA. CONCLUSIONS: First, colonocytes use the same epitopes on CEA and CD44 as colorectal carcinoma cells to adhere to solid-phase CEA. Second, colonocytes bind to solid-phase CEA through CEA-to-CEA homophilic binding. Third, CEA and type IV collagen, but not laminin, are adhesion ligands for human colonocytes.

Antibodies↗
PubMed1994

Simulated microgravity does not alter epithelial cell adhesion to matrix and other molecules.

Microgravity has advantages for the cultivation of tissues with high fidelity; however, tissue formation requires cellular recognition and adhesion. We tested the hypothesis that simulated microgravity does not affect cell adhesion. Human colorectal carcinoma cells were cultured in the NASA Rotating Wall Vessel (RWV) under low shear stress with randomization of the gravity vector that simulates microgravity. After 6-7 days, cells were assayed for binding to various substrates and compared to cells grown in standard tissue culture flasks and static suspension cultures. The RWV cultures bound as well to basement membrane proteins and to CEA, an intercellular adhesion molecule, as control cultures did. Thus, microgravity does not alter epithelial cell adhesion and may be useful for tissue engineering.

Basement Membrane↗
PubMed1994

Complementation group assignments of moderately UV-sensitive CHO mutants isolated by large-scale screening (FAECB).

The complementation group (CG) assignment is presented for 74 moderately sensitive (approximately 2-4x sensitivity of parental line based on ratio of D10s) UV-sensitive mutants of Chinese hamster ovary (CHO) cells from the Facility for Automated Experiments in Cell Biology (FAECB) collection. The distribution of mutants within the first five rodent UV CGs was similar to that of previously reported highly sensitive (> 4x wild-type UV sensitivity) mutants from this collection. This analysis nearly completes the identification of this large collection of over 200 mutant lines isolated after screening an estimated 3 million total colonies of mutagenized CHO cells from approximately 20 mutant hunts with up to about 400,000 colonies screened. Only eight lines with less than about 2x parental line UV sensitivity remain unassigned. One CG of UV mutants (CG6), which now has five identified representatives in the collection, has only been found among moderately UV-sensitive CHO cells. Mutant UV40, a mitomycin C (MMC)- and X-ray-sensitive line with moderate UV cross-sensitivity, is not in CGs 1-6 and apparently is not a nucleotide excision repair mutant. Also identified were new alleles of CG1 and CG4 mutants with profoundly deficient unscheduled DNA synthesis and moderate UV sensitivity but low sensitivity to MMC. The first CG5 mutant derived from MMC-sensitive MC5 cells has been identified as the second CG5 mutant in the collection. No representatives of rodent CGs 7-11 were found, suggesting that AA8 cells have a chromosomal makeup that precludes easy isolation of mutants in these CGs.

Animals↗
PubMed1994

Growth inhibition of follicular small-cleaved-cell lymphoma cells in short-term culture by interleukin-3.

BACKGROUND: The role of interleukin-3 (IL-3) in stimulating the growth of early myeloid progenitor cells is very well established. Therefore, IL-3 has been incorporated into many post-bone-marrow transplantation and intensive chemotherapy programs for the treatment of solid tumors and hematologic malignancies, including lymphomas. However, the effect of IL-3 on normal and malignant lymphocytes has not been well studied. PURPOSE: The purpose of this study was to evaluate the in vitro effect of IL-3 on the growth of follicular small-cleaved-cell lymphoma (FSCCL). MATERIALS AND METHODS: IL-3 receptor expression on the surface of CD19+ cells was determined by two-color flow cytometry measuring the receptor-binding of biotinylated IL-3 to CD19+ B-cells. Seven cases of FSCCL were compared to six normal controls. Cell proliferation was evaluated by [3H]thymidine incorporation into cells grown in suspension cultures. RESULTS: All seven cases of FSCCL expressed the IL-3 receptor on the surface of CD19+ cells, whereas all six cases of CD19+ cells isolated from the peripheral blood of normal donors did not express IL-3 receptors. IL-3 had antiproliferative activity against FSCCL as manifested by a decrease in [3H]thymidine incorporation and a decrease in the total number of cells after 72 hours of culture. CONCLUSION: IL-3 inhibits the growth of FSCCL cells in vitro. Clinical trials to evaluate the in vivo effect of IL-3 in patients with FSCCL are warranted.

Antigens, CD↗
PubMed1994

Nonpenetrating trauma to the carotid artery: seven cases and a literature review.

Nonpenetrating carotid trauma is uncommon and frequently missed on initial examination. The cases of seven patients seen over a period of 21 years are presented and 100 cases from the most recent literature are reviewed. Causes and mechanisms of injury, clinical presentation, investigations, management, and outcome are discussed. Causes of injury were three motor vehicle collisions, two falls, one sports injury, and one blow to the face. Clinical presentation was early in four and delayed in three. The earliest symptoms and signs were a change in mental status, headache, unprovoked fall, focal weakness, neglect, and dysphasia. Doppler studies may be useful in screening, but a definitive diagnosis is made with the help of angiography. Two patients were treated surgically; one died, one with delayed symptoms from a pseudoaneurysm recovered completely. Five patients were given anticoagulants; all survived with permanent deficits related to their pretreatment neurologic status. The outcome in 100 recent cases from the literature has improved compared with previous reports. The overall mortality was 12%. The outcome in our seven cases supports recent trends toward a strategy of early anticoagulation and selective surgical treatment.

Adult↗
PubMed1994

How can nurses build trusting relationships with people who have severe and long-term mental health problems? Experiences of case managers and their clients.

Despite the shift in recent policy toward people with severe and long-term mental health problems, there is considerable evidence that mental health nurses tend to prioritize clients with acute, neurotic or short-term problems and become demoralized when working with people with persistent needs and disabilities. Mental health nurses need to find ways of developing effective relationships with these people in order to offer a service which the client is not only willing to engage in, but takes an active part in, and which allows care providers to derive satisfaction from their work. Through 46 in-depth interviews with case managers (working specifically with people with long-term mental health problems) and their clients, this qualitative study provides some guidelines for mental health nurses working in this field. Analysis of the interviews revealed that both clients and case managers focused on the problems and strategies associated with developing and maintaining relationships with one another. Furthermore, the interviews suggested that case managers adopted a philosophy for working that enabled both clients and case managers to feel positive about the work. The principles of this value base, and the way it was used in the process of case management, are explored in this account.

Adult↗
PubMed1994

Dihydroergotamine nasal spray for the acute treatment of migraine.

We conducted a multicenter, double-blind, parallel-group study to compare the efficacy and safety of dihydroergotamine (DHE) nasal spray and placebo over 4 hours in the treatment of migraine. Of the 112 patients enrolled, 100 were included in the "intent-to-treat" efficacy analysis. The patients self-administered either 2.0 mg DHE (0.5 mg per nostril, repeated after 15 minutes) or placebo at the onset of two separate headaches and rated hourly the drugs' effects on pain severity, pain relief, nausea, and vomiting. The physicians assessed the overall effectiveness of the drugs in relieving headache pain, nausea, and vomiting. Both the patients' and physicians' ratings indicated that DHE was significantly superior to placebo in improving headache and nausea; according to the patients' ratings, these between-group differences were already significant at the first (hour 1) evaluation. There were no significant differential treatment effects with respect to relief of vomiting. Most adverse events were mild or moderate, confined to the nasopharyngeal area, and probably related to the route of administration. We conclude that DHE nasal spray is a safe and effective treatment for the pain and nausea of migraine attacks.

Administration, Intranasal↗
PubMed1993

Adhesion to carcinoembryonic antigen by human colorectal carcinoma cells involves at least two epitopes.

Carcinoembryonic antigen (CEA) may be involved in both cell-cell and cell-substrate adhesion. Our purpose was to determine whether epitopes involved in the homophilic binding of human colorectal carcinoma cells to CEA participated in adhesion to basement membrane proteins. Three human colorectal adenocarcinoma cell lines and one CHO cell line transfected with CEA cDNA were tested in a solid-phase adhesion assay. The 2 CEA-expressing carcinoma cell lines (KM-12c and CCL 188) and the transfectant, but not the parental CHO line, bound to CEA. The CEA-non-producing carcinoma line (Clone A) did not bind to CEA. All colorectal carcinoma cell lines, the transfectant and the parental CHO line bound to laminin, while the colorectal carcinoma lines bound to type-IV collagen. MAbs to epitopes on CEA that cross-react with non-specific cross-reacting antigen (NCA) inhibited adhesion of CEA-expressing cells to CEA. MAbs to non-cross-reactive epitopes of CEA did not block adhesion to CEA. When the inhibitory anti-CEA antibodies were compared in a competitive radioimmunoassay, 2 distinct epitopes were identified. Epitope I is in the N-terminal domain and defined by MAbs MN3, T84.1 and C110, whereas epitope II is located in the repeating loop domains and is recognized by antibodies MN15, PR3B10 and NP1. None of the antibodies to epitope I or II blocked adhesion by KM-12c or CCL 188 cells to laminin or type-IV collagen. Thus, at least 2 different regions on CEA participate in adhesion to CEA but not to collagen or laminin by CEA-expressing human colorectal carcinoma cells.

Adenocarcinoma↗
PubMed1993

Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2'-deoxyadenosine and 9-beta-D-arabinosyl-2-fluoroadenine.

2-Chloro-2'-deoxyadenosine (CldAdo) and 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A) have shown marked activity in the treatment of indolent lymphoid malignancies. Based on the susceptibility of various lymphocyte populations to apoptosis, we investigated whether CldAdo or F-ara-A would induce this process in lymphocytes from patients with chronic lymphocytic leukemia (CLL). In vitro exposure of leukemic lymphocytes to CldAdo or F-ara-A for 24 to 72 hours elicited features of apoptosis visible by light and electron microscopy. Analysis of DNA integrity showed DNA cleavage into nucleosomal-sized multimers. Using a quantitative assay, drug-induced DNA fragmentation was both time and dose dependent. Inhibition of active macromolecular synthesis did not prevent drug-induced fragmentation; however, both drug-induced and spontaneous DNA fragmentation were prevented by intracellular calcium chelation. In vitro culture with phorbol ester generally decreased drug-induced DNA cleavage. After prolonged incubation, CLL cells exhibited spontaneous cleavage; albeit, at significantly lower rates than drug-treated cells. Heterogeneity was observed for spontaneous and drug-induced DNA fragmentation and was significantly lower in B-leukemic cells obtained from patients with high-risk and refractory disease. We conclude that CldAdo and F-ara-A are potent inducers of apoptotic death in CLL and that this feature correlates with the disease status.

Adenosine Triphosphate↗
PubMed1993

Modulation of SPARC expression during butyrate-induced terminal differentiation of cultured human keratinocytes: regulation via a TGF-beta-dependent pathway.

Expression of SPARC (secreted protein acidic and rich in cysteine), a 43-kDa extracellular matrix-associated glycoprotein involved in tissue remodeling, was quantitated during normal human keratinocyte (NHK) growth in culture and as a function of sodium n-butyrate (NaB)-induced differentiation to mature enucleate cornified envelopes (CEs). Low levels of SPARC expression were observed in the basal-like cells of control NHKs, with isolated cells showing intense SPARC expression on the ventral surface. After addition of NaB, SPARC expression increased and the pattern of expression shifted to one involving predominantly suprabasal cells (i.e., spinous cells, pre-CEs, and mature CEs). Dense deposits of SPARC often surrounded the mature CEs. Flow cytometric analysis indicated that approximately 13% of NHKs expressed SPARC within 24 h of seeding into culture. This fraction of SPARC+ cells increased with time and peaked immediately postconfluence (31.3 +/- 6.3% SPARC+). Cellular SPARC expression then decreased to baseline levels during entrance into plateau phase growth. SPARC was detectable in all phases of the cell cycle. SPARC levels were more intense and heterogeneous within the G2/M and G1 phases while S phase cells exhibited relatively homogeneous, low intensity, SPARC expression. During NaB-induced NHK differentiation, SPARC intracellular content increased prior to the onset of CE formation (i.e., 2 days after its addition) followed by a period of extracellular accumulation which coincided with the time of maximal CE generation (i.e., Days 4 and 5 after NaB addition). Correlation of cell size with anti-SPARC immunoreactivity revealed a predominance of SPARC expression in cells with a suprabasal phenotype. NHKs cultured on fibronectin (FN), an established modulator of epidermal cell maturation in vitro, showed a similar response to NaB. In general, however, the level of NaB-induced SPARC expression was considerably reduced in FN cultures correlating with a lower efficiency of CE formation. Induced SPARC expression was, in large part, dependent on autocrine transforming growth factor-beta (TGF-beta) production since incubation in the presence of NaB+neutralizing antibodies to TGF-beta inhibited both the expression of SPARC by 72% and development of mature CEs.

Antibodies↗
PubMed1993

CD44 participates in the adhesion of human colorectal carcinoma cells to laminin and type IV collagen.

CD44 is a cellular adhesion molecule expressed in many different types of cells that may be a receptor for hyaluronic acid, laminin, collagen or fibronectin. In this study, we determined whether CD44 participated in the adhesion of three human colorectal carcinoma cell lines (KM-12c, CCL 188 and MIP-101) to laminin, collagen and hyaluronic acid. All lines were positive for the epithelial form of CD44 (CD44E) with a molecular weight of approximately 160 kD. All of them bound significantly to laminin and type IV collagen but not to hyaluronic acid in a solid phase adhesion assay. Three monoclonal antibodies to CD44 (Hermes 1, Hermes 3 and J173) significantly blocked the binding of colorectal carcinoma lines to laminin and collagen whereas another antibody to CD44 (50B4) bound to cells but did not inhibit adhesion. Only Hermes 1 completely abolished the binding to hyaluronic acid by a human B lymphoblastoid cell line, JY, that expressed the 90 kD haematopoietic form of CD44. Soluble hyaluronate inhibited the adhesion of JY cells to solid phase hyaluronate but did not inhibit adhesion to laminin and collagen by the colorectal carcinoma lines. Thus, (a) CD44E participates in the adhesion of colorectal carcinoma cells to laminin and type IV collagen and (b) the binding site for laminin and collagen on CD44E is different from the site for hyaluronic acid.

Antibodies, Monoclonal↗
PubMed1993

Carcinoembryonic antigen: enhancement of liver colonisation through retention of human colorectal carcinoma cells.

Carcinoembryonic antigen (CEA) is an oncofetal antigen whose function in the progression of colorectal carcinoma remains unclear although recent studies suggest it participates in homotypic cellular adhesion. We have previously shown that 40 micrograms of CEA injected intravenously into athymic nude mice enhances experimental metastasis in liver and lung by two human colorectal carcinoma cell lines that are injected intrasplenically 30 min later. The metastatic potential of another three moderately to highly metastatic colorectal carcinoma cell lines and of one weakly metastatic line has now been analysed in this model. CEA pretreatment only enhanced colony formation by cell lines that were weakly metastatic in untreated nude mice; it did not affect experimental metastasis by highly metastatic lines. CEA pretreatment enhanced the retention of 125I Idudr-labelled weakly metastatic tumour cells within the liver and lungs 4 h after intrasplenic injection but not the retention of highly metastatic tumour cells or inert latex beads. A significant correlation existed between the formation of experimental metastases and the early retention of tumour cells within the liver after intrasplenic injection. Aggregation did not appear to be important for retention in liver because CEA did not aggregate colorectal carcinoma cells in vitro. Also CEA did not alter natural host effector cell function in a cytolysis assay in vitro. We suggest that CEA facilitates liver colonisation by three of eight human colorectal carcinomas in athymic nude mice by increasing the hepatic retention of tumour cells. The potential mechanisms by which CEA may increase the retention of tumour cells in the liver are discussed.

Animals↗
PubMed1992

Prognostic value of proliferating cell nuclear antigen expression in chronic lymphoid leukemia.

Chronic lymphocytic leukemia (CLL) is a usually indolent disease that can assume an aggressive clinical course in some patients. To develop assays that would be predictive of how a particular patient's disease would evolve, we studied the expression of proliferating cell nuclear antigen (PCNA) by Western blotting in 40 patients with CLL. The concentration of PCNA, a cofactor for delta DNA-dependent DNA polymerase, is indicative of the proliferative state of the cell. Significantly lower PCNA levels were observed in earlier stage CLL when compared with more advanced disease. The leukemic cell proliferative rate, assessed by lymphocyte doubling time and flow cytometry, also correlated significantly with the level of PCNA expression. These results suggest that a high level of PCNA in the cells of CLL patients at presentation identifies a subgroup of patients whose CLL cells have a higher proliferative activity and who may, therefore, have a potentially shorter survival.

Actins↗
PubMed1992

Transient expression of the coat protein of sugarcane mosaic virus in sugarcane protoplasts and expression in Escherichia coli.

The coat protein (CP) of strain SC of sugarcane mosaic virus (SCMV-SC) was expressed transiently in sugarcane protoplasts after electroporation with one of two plasmids encoding the CP gene. The CP gene was fused with either the cauliflower mosaic virus 35S promoter or the synthetic monocotyledon promoter "Emu". The coat protein gene was also inducibly expressed in Escherichia coli when fused to the trc promoter. The protein expressed in both systems had the same electrophoretic mobility and antigenic specificity as purified SCMV-SC coat protein. Transient expression of the 35S-CP gene in protoplasts could only be demonstrated in Western blots developed with the chemiluminescence enzyme substrate luminol.

Base Sequence↗