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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 235 records · Page 13Linked to original sources
PubMed1992

Prosthetic hip-joint infection associated with a penicillin-tolerant group B streptococcus.

We report a case of prosthetic hip-joint infection with Streptococcus agalactiae (Lancefield group B streptococcus). The infection recurred after 3 months' treatment with amoxycillin. On further investigation, the isolate was found to be amoxycillin-tolerant. Addition of gentamicin abolished tolerance in vitro and the patient has remained asymptomatic since receiving a 10-day course of amoxycillin and gentamicin followed by amoxycillin alone.

Aged↗
PubMed1992

Neuroendocrine and epithelial markers in diagnostic bronchial lung cancer biopsy specimens.

The incidence of neuroendocrine and epithelial markers was investigated by immunocytochemistry in archival, lung cancer, bronchial biopsy specimens (n = 48). No correlation of antigenicity with histological type was observed. 79% non-small cell lung carcinoma (NSCLC) and 61% small cell lung carcinoma (SCLC) were positive for epithelial markers. HuTu-m3 did not discriminate adenocarcinomas and squamous cell carcinomas from SCLC. 83% SCLC and 93% NSCLC were positive for one or more neuroendocrine marker. Multiple neuroendocrine markers were found in 61% SCLC, 83% NSCLC and 83% squamous cell carcinomas, this incidence being greater in the NSCLC group, and in the squamous carcinomas in particular, than previously reported.

Antibodies↗
PubMed1992

Development of a quantitative in vitro transformation assay for kidney epithelial cells.

A quantitative in vitro transformation assay has been developed for the first time using primary rat kidney epithelial (RKE) cells. RKE cells were grown in a 50:50 mixture of 3T3 conditioned medium and DF8 medium composed of Ham's F-12/DMEM supplemented with ferrous sulfate, vasopressin, transferrin, sodium selenite and 10% fetal bovine serum. Colony forming efficiency of cells plated in this medium was high, ranging from 2.4 to 16%. Normal RKE cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) became transformed to a preneoplastic state of enhanced in vitro growth potential and formed large colonies of morphologically altered cells, whereas RKE cells treated with vehicle alone ceased proliferating and/or sloughed off the dish within 4-6 weeks. Relative survival and percent transformation frequency (Tf) of RKE cells exposed to MNNG were inversely proportional and both were dose dependent. MNNG concentration of 0.5, 1.0 and 2.0 micrograms/ml resulted in transformation frequencies of 0.13, 0.37 and 1.1% respectively (n = 4). Morphologically transformed colonies gave rise to cell lines with indefinite growth capacity and neoplastic potential. One of six transformed RKE cell (TRKE) lines injected into nude mice produced adenocarcinomas. This assay represents the first in vitro model for studying mechanisms of chemical transformation of normal kidney epithelial cells and may also be useful as a screen for identifying potential renal carcinogens.

Animals↗
PubMed1992

Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience.

BACKGROUND: Several metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty. METHODS AND RESULTS: To determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis > or = 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p = 0.02) and upon whether or not a poststent stenosis < or = 0% was achieved (6% versus 33%, p = 0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent. CONCLUSIONS: Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed.

Coronary Angiography↗
PubMed1992

Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage.

Activation of lymphocyte subpopulations was determined in conjunction with levels of cytokines in peripheral blood and bronchoalveolar lavage (BAL) of asthmatics. Allergic asthmatics had increased numbers of CD4+ IL-2R+ T cells in peripheral blood and BAL, and T-cell activation closely correlated with numbers of low-affinity IgE receptor (CD23) bearing B cells. In contrast, in nonallergic asthmatics both CD4+ and CD8+ T cells from blood and BAL had increased expression of IL-2R, HLA-DR, and VLA-1. Furthermore, in the nonallergic asthmatics CD8+ T cells were decreased in blood but increased in BAL. Cytokine levels were determined in BAL fluid and supernatants from purified peripheral blood T cells and enriched BAL lymphocyte preparations. Allergic asthmatics were characterized by increased levels of IL-4 and IL-5, and this elevated IL-4 contributed to the elevated IgE levels found in these allergic subjects. In contrast, nonallergic asthmatics had elevated levels of IL-2 and IL-5, with IL-2 contributing to T-cell activation. In both types of asthma, the close correlation of IL-5 levels with eosinophilia suggests that IL-5 is responsible for the characteristic eosinophilia of asthma. Thus, we provide evidence of distinct T-cell activation resulting in different spectra of cytokines in allergic and nonallergic asthma.

Adolescent↗
PubMed1992

Expression of neuroendocrine and epithelial markers in an adherent subline derived from a classic small cell lung cancer cell line.

Small cell lung cancer (SCLC) cell lines usually grow as floating aggregates, in contrast to the adherent monolayers formed by non small cell lung cancer (NSCLC). Induction of an adherent phenotype by a variety of methods has been the subject of a number of recent publications. In this study, cultivation of the classic SCLC cell line, NCI-H69, on a substratum provided by the pretreatment of tissue culture dishes with medium conditioned by the growth of a well differentiated squamous carcinoma cell line, HN5, induced an adherent phenotype with a variety of epithelioid morphologies, commencing within 24 hr of plating. From such cultures an adherent subline, H69A, has been established, which differs in its growth, morphological characteristics, and immunocytochemical marker expression from the parent NCI-H69 cells, and in its marker expression from other adherent SCLC cell lines. H69A retained expression of neural cell adhesion molecule (NCAM) and the neuroendocrine markers neuron specific enoclase, chromogranin A, and synaptophysin, but showed diminished expression of the epithelial cell surface markers AUA1, Ber-EP4, epithelial membrane antigen (EMA), and desmosomal protein. Compared to NCI-H69 cells, the amounts of cytokeratin 18 detected were elevated, while those of cytokeratin 19 were diminished in H69A cells. Focal expression of cytokeratin 4 was found in some H69A cells, indicative of a capacity for partial squamous differentiation. The expression of the cell surface glycoproteins detected by AUA1 and Ber-EP4 was reduced throughout cultivation of the H69A subline, while that of EMA and desmosomal protein was further diminished with continued passage. Changes in the expression of these markers and NCAM were evident in NCI-H69 cells grown on an HN5-derived substratum.

Antigens, Differentiation↗
PubMed1992

Cytogenetic and molecular correlates between rodent and human renal cell carcinoma.

In man, RCC makes up the largest proportion of primary kidney cancers, comprising approximately 85% of renal tumors and accounting for approximately 2% of the cancer deaths each year (Richie and Skinner 1981). As shown in Table 2, there are many similarities between spontaneous rat RCC and human RCC. Therefore, rat RCC and the Eker rat model in particular appear to be well suited to investigations into the mechanisms by which this disease occurs. In addition, animal models such as the Eker rat may also be valuable as human surrogates for developing and testing new approaches for treatment of human renal cancer.

Animals↗
PubMed1992

Cognitive behavioral treatment of fibromyalgia syndrome: preliminary findings.

We used a simple quasiexperimental design to assess the efficacy of an inpatient cognitive-behavioral treatment program for persons with fibromyalgia syndrome (FS). Twenty-five participants were assessed on 3 occasions: (1) about 5 months before admission to the program, (2) on admission and (3) at discharge. In addition, the dependent variables (pain response measures) were divided into "target" (expected to change with treatment) and "nontarget" (not expected to change) to assess potential demand characteristics. Our results showed that, whereas no changes occurred in either target or nontarget variables between the initial assessment and admission, consistent changes were observed only in target variables between admission and discharge. Our data provide preliminary support for cognitive-behavioral treatment for FS.

Adolescent↗
PubMed1991

An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils.

A simple method is described for the isolation of human peripheral blood eosinophils by an immunomagnetic procedure. Superparamagnetic particles were coupled to a monoclonal antibody against CD16, a molecule present on neutrophils but not on eosinophils. A peripheral blood granulocyte preparation, containing neutrophils and eosinophils, was incubated with these anti-CD16 particles. In the magnetic field of a permanent magnet, magnetically labelled neutrophils were then retained on columns with a ferromagnetic matrix. By this negative selection procedure, eosinophils of 99.5% purity were obtained from normal individuals and 99.6% purity from patients with eczema. A comparison was made between the immunomagnetic method and eosinophil isolation after N-formyl-methionyl-leucyl-phenyl-alanine treatment. Even in the case of individuals with very low eosinophil counts, the immunomagnetic method permits the efficient isolation of highly purified and functionally active eosinophils.

Antigens, CD↗
PubMed1991

Hereditary renal cell carcinoma in the rat associated with nonrandom loss of chromosomes 5 and 6.

A spontaneous form of renal cell carcinoma occurs in rats that arises as the result of the inheritance of a mutation in a single autosomal gene. Cytogenetic analysis was performed on seven cell lines and four primary tumor cell preparations derived from this hereditary form of renal cell carcinoma. Banded karyotypes prepared from these seven lines exhibited loss and/or partial deletion of both chromosomes 5 and 6. Translocations involving chromosome 4, resulting in a net loss of genetic material located near the centromere (4q11), were observed in three of the cell lines. Monosomy, translocation, and breakage of chromosome 5 involving band 5q31 and monosomy and partial deletion of chromosome 6 involving band 6q22-q24 were independently observed in primary tumor cells from three of four tumors examined. Monosomy of chromosome 4 was observed in cells from a single tumor. The smallest region of deletion of chromosome 6 common to all the cell lines and tumor cells was 6q24, suggesting the presence of a tumor suppressor gene at this locus. These results indicate that loss of genes located on chromosomes 4, 5, and 6, possibly tumor suppressor gene(s), may be important for tumor development and/or progression in rat renal cell carcinoma and is consistent with the hypothesis that a gene locus on one of these chromosomes may be the site of the original predisposing mutation.

Animals↗
PubMed1991

Trisomy of rat chromosome 1 associated with mesothelial cell transformation.

Identification of specific chromosomal aberrations in transformed mesothelial cells is an important step in elucidating the mechanism of transformation of these cells which are targets for occupational and environmental carcinogens, such as asbestos fibers. Cytogenetic analysis of normal rat mesothelial cell lines revealed that at late passage (p20-p34), trisomy of chromosome 1 was present in greater than 80% of the cells in four spontaneously immortalized lines examined, whereas at early passage (p8-p10), only 15-44% of the cells had trisomy 1. Trisomy of chromosome 1 had increased in the population as a function of passage, suggesting that cells with trisomy 1 had a selective growth advantage under in vitro culture conditions and that this alteration was associated with transformation. A commercially available rat mesothelial cell line (4/4 RM4, ATCC), was also found to have a duplication of a portion of the long arm of chromosome 1. To determine if chromosome 1 alterations have relevance to the transformed phenotype in vivo, a neoplastic cell line was established from a spontaneous rat mesothelioma. At passage 15, trisomy of chromosome 1 was observed in 26% of the metaphases in this line. However, when these cells were injected into nude mice, 99% of the cells from the resulting tumor contained an additional copy of chromosome 1. Therefore, trisomy 1 also conferred a selective growth advantage in vivo and/or was associated with the malignant subpopulation in the tumor derived cell line. These studies suggest that chromosome 1 contains a gene(s) involved in transformation of rat mesothelial cells.

Animals↗
PubMed1991

Structural and functional studies of the endothelial activation antigen endothelial leucocyte adhesion molecule-1 using a panel of monoclonal antibodies.

We have produced a panel of mAb to the endothelial activation Ag endothelial leucocyte adhesion molecule-1 (ELAM-1), using both a conventional immunization protocol and one involving immunosuppression. By constructing ELAM-1 mutants we have demonstrated that seven of these antibodies recognize epitopes within the lectin domain of ELAM-1 and that one binds within the complement regulatory protein domains. These studies also suggest that the EGF-like domain is important in maintaining the conformation of the neighbouring lectin domain. In functional studies, U937 cells bound to Cos cells expressing either ELAM-1 or ELAM-1 with the complement regulatory protein domains deleted. No adhesion was observed to Cos cells expressing ELAM-1 mutants lacking either the lectin or EGF-like domains. The fact that antibodies directed against the lectin domain can inhibit adhesion suggest that this domain is directly involved in cell binding.

Antibodies, Monoclonal↗
PubMed1991

Altered expression of transforming growth factor-alpha in hereditary rat renal cell carcinoma.

A hereditary form of renal cell carcinoma exists in rats that results from a single gene mutation and is histologically similar to that described in humans. Cell lines derived from these rat tumors were shown to express abundant transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF)-receptor RNA transcripts, but no EGF mRNA. In contrast, normal kidney expressed EGF and EGF-receptor transcripts, but TGF-alpha transcripts were barely detectable. Other kidney epithelial cell lines examined (NRK 52E, MDCK, and LLCPK) were negative for expression of both TGF-alpha and EGF transcripts, but expressed EGF receptors. In addition, the renal cell carcinoma-derived lines secreted TGF-alpha into the media. Immunohistochemistry of normal kidney with a TGF-alpha specific antibody revealed a characteristic pattern of staining of collecting ducts and, to a lesser degree, proximal tubules. In the neoplastic kidney tissue, both the cystic and solid portions of the tumors displayed intense immunoreactivity, indicating that altered expression of this growth factor by the transformed cells occurred in situ. These results suggest that altered TGF-alpha expression is an important aspect of the neoplastic phenotype in rodent as well as human renal cell carcinoma, and support the use of this hereditary rodent tumor model for studying the pathogenesis of this disease.

Animals↗
PubMed1991

The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system.

The floor plate is a set of epithelial cells present in the ventral midline of the neural tube in vertebrates that seems to have an important role in the developmental patterning of central nervous system fibre pathways, and arrangements of specific neurons. The floor plate arises from dorsal ectodermal cells closely associated with the mesoderm that forms notochord, and it may depend on interactions from the notochord for its specification. To learn the nature of these interactions we have analysed mutations in zebrafish (Brachydanio rerio). We report here that in wild-type embryos the floor plate develops as a simply organized single cell row, but that its development fails in embryos bearing the newly discovered zygotic lethal 'cyclops' mutation, cyc-1(b16). Mosaic analysis establishes that cyc-1 blocks floor plate development autonomously and reveals the presence of homeogenetic induction between floor plate cells.

Animals↗
PubMed1991

T cell subsets and their soluble products regulate eosinophilia in allergic and nonallergic asthma.

Lymphokines derived from activated T cells regulate the proliferation and postmitotic differentiation of eosinophils in vitro. We investigated whether peripheral blood eosinophilia, which is a characteristic feature of both allergic and nonallergic asthma, correlates with T cell activation and lymphokine production in asthmatic patients. Flow cytometric analysis of T cell activation markers revealed that asthmatic individuals are characterized by increased numbers of IL-2R (CD25)-bearing T cell subsets. The absolute number of IL-2R+ T cells correlated with the eosinophilia observed in the asthmatic patients. Purified CD4+ and CD8+ T cells from allergic and nonallergic asthmatic individuals spontaneously secreted factors that extend the lifespan of eosinophils in vitro. T cells from normal donors displayed this effect only after polyclonal stimulation with anti-CD3 antibody. The eosinophil lifespan-extending factors were also found in sera of asthmatic patients. Identification of these factors was performed by using neutralizing antibodies against IL-3, IL-5, and granulocyte-macrophage CSF. In sera, mainly IL-5 and granulocyte-macrophage CSF were responsible for prolonged eosinophil survival, whereas granulocyte-macrophage CSF was dominant in T cell supernatants. These results indicate that T cells and secretion of lymphokines play an important regulatory function toward eosinophils, which are thought to represent major proinflammatory effector cells in certain types of asthma.

Adult↗