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Biomedical subjects

C L Walker

Publications and source records attributed to C L Walker.

At least 19 recordsLinked to original sources
PubMed1995

Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II.

Insulin-like growth factors (IGFs) are polypeptides that play an important role in cellular proliferation and differentiation. The present study examines the role of IGFs in the growth of mesothelial cells. Cell lines derived from normal rat mesothelium as well as lines derived from spontaneous rat mesotheliomas were found to express RNA transcripts for IGF-II. In contrast, cell lines derived from asbestos-induced rat mesotheliomas did not express this growth factor. All cell lines expressed receptors for IGF-I and IGF-II, as well as insulin receptors. Coexpression of IGF-II and its cognate receptor suggested that IGF-II was acting as an autocrine growth factor in the spontaneously immortalized cells and the cells derived from the spontaneous tumors. The biological activity of IGF-II secreted by the cell lines into conditioned medium could be neutralized using an IGF-II-specific antibody. Growth was inhibited in a dose-dependent manner; at the highest antibody concentration used (100 micrograms anti-IGF-II/ml), cell growth was decreased to 47% of control values. This inhibition was partially reversible by treatment of the cultures with IGF-II (91% of the control). These data suggest that IGF-II expression may be involved in the spontaneous alteration of rat mesothelial cells and may function as an autocrine or paracrine growth factor to modulate the growth of these cells in vitro and in vivo. Ubiquitous expression of IGF-II by cells that have not been exposed to asbestos and the lack of IGF-II expression by asbestos-transformed cells suggest that the mechanisms of changes in growth factor expression differ in mesothelial cells transformed by different pathways.

Animals↗
PubMed1995

Association of rat p15INK4B/p16INK4 deletions with monosomy 5 in kidney epithelial cell lines but not primary renal tumors.

Recently the putative tumor suppressor gene p16INK4 was mapped to human chromosome 9p21, which is homologous to rat chromosome 5. Monosomy of rat chromosome 5 occurs with high frequency in rat kidney tumor-derived cell lines (ERC lines). Thus, we studied these lines in order to investigate the involvement of p15INK4B and p16INK4 in the genesis of this tumor type. p15INK4B and p16INK4 were found by Southern blot analysis to be codeleted in five of seven of these lines. This was confirmed by Northern blot analysis with a probe for the rat p15INK4B gene. In normal rat tissues, expression of p15INK4B was abundant in lung (2.5 and 2.0 kilobases), less abundant in testis (2.5, 2.0, 1.1, and 0.9 kilobases), barely detectable in liver (2.0 kilobases), and not detectable in neonatal kidney, adult kidney, brain, heart, or spleen. In the ERC lines, p15INK4B was expressed as a single 2.0-kilobase transcript observed only in those cell lines in which the gene was detected by Southern blot analysis. However, neither p15INK4B nor p16INK4 were deleted in 12 of 12 primary kidney tumors examined, suggesting that deletion of these genes is not directly involved in the process of renal tumor development but may be related to tumor progression or autonomous growth in vitro. A panel of rat kidney epithelial cell lines chemically transformed in vitro (TRKE lines) that had high-frequency monosomy 5 were also examined, but deletion of p15INK4B and p16INK4 was observed in only one of six of the TRKE lines. To our knowledge, this is the first reported investigation of these genes in rodent tumors and cell lines, and its data support the theory that alterations of genes located in the INF region of rat chromosome 5 may play a role in rodent cell transformation.

Animals↗
PubMed1995

Allelic loss at the tuberous sclerosis 2 locus in spontaneous tumors in the Eker rat.

Somatic events leading to the inactivation of tumor suppressor genes often involve chromosomal alterations that can be detected as loss of heterozygosity (LOH). In the Eker rat, spontaneous tumors of the kidney, uterus, and spleen develop as a result of a germline mutation of the tuberous sclerosis 2 (Tsc2) gene. We examined the pattern and frequency of LOH at the predisposing locus in 77 primary tumors and cell lines to gain an understanding of the role of Tsc2 allelic loss in the pathogenesis of Eker-derived tumors. Although most renal and uterine tumors (primary and cell lines) displayed LOH, splenic hemangiosarcomas did not. Although the presence of normal tissue may account for some of this difference, the possibility exists that an alternative mechanism, such as subtle mutation or gene dosage effects, may be involved during splenic tumorigenesis. Northern analysis confirmed that LOH resulted in loss of the wild-type transcripts for the Tsc2 gene. Thus, the inactivation of both alleles plays an important role in renal and uterine tumor development, in keeping with Knudson's two-hit hypothesis. In addition, renal tumors that retained the wild-type allele also did not express the normal transcript, suggesting that the remaining Tsc2 alleles had acquired subtle mutations resulting in loss of gene function.

Alleles↗
PubMed1995

Colocalization of the rat homolog of the von Hippel Lindau (Vhl) gene and the plasma membrane Ca++ transporting ATPase isoform 2 (Atp2b2) gene to rat chromosome bands 4q41.3-->42.1.

Using fluorescence in situ hybridization, we localized the rat homolog of the von Hippel-Lindau gene (Vhl) to rat chromosome band 4q41.3-->q42.1. We also mapped the gene encoding the plasma membrane Ca(++)-transporting ATPase isoform 2(Atp2b2) to the same chromosome subregion. These two genes together with Raf1 appear to be members of a large syntenic gene cluster that maps to human chromosome bands 3p25-->p26, mouse chromosome bands 6 C3-->E, and rat chromosome bands 4q41-->q42. Cytogenetic analysis of NRK 52E cells derived from immortalized normal rat kidney epithelial cells revealed an inverted duplication of the region containing this gene cluster.

Animals↗
PubMed1994

Characterization of cell lines derived from formaldehyde-induced nasal tumors in rats.

Cell lines derived from formaldehyde-induced nasal tumors in Fischer 344 rats were established. All of the lines were found to be epithelial and aneuploid and to express keratin, transforming growth factor-alpha, and epidermal growth factor receptor transcripts. Two of four lines were tumorigenic upon injection into nude mice, and these lines also contained point mutations in the p53 suppressor gene. The data indicate that these lines possess characteristics that make them a valuable tool for the study of chemically induced respiratory tract carcinogenesis.

Animals↗
PubMed1992

Arthroscopic fixation of osteochondritis dissecans. Outpatient treatment for condylar defects.

According to a 1990 study, 88% of the patients assessed their postoperative result as excellent or good after two years of follow up. One disadvantage to this repair is the need for a second arthroscopy for compression screw removal; however, this allows the surgeon an opportunity to assess healing. Surgeons are continuing to advance arthroscopic surgery by using supplemental bone grafts, with or without compression screw fixation. Arthroscopic compression screw fixation of osteochondritis dissecans is a progressive alternative for patients who may otherwise have been candidates for an open-knee arthrotomy.

Ambulatory Surgical Procedures↗
PubMed1992

Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome.

A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.

Animals↗
PubMed1991

The Barr body is a looped X chromosome formed by telomere association.

We examined Barr bodies formed by isodicentric human X chromosomes in cultured human cells and in mouse-human hybrids using confocal microscopy and DNA probes for centromere and subtelomere regions. At interphase, the two ends of these chromosomes are only a micron apart, indicating that these inactive X chromosomes are in a nonlinear configuration. Additional studies of normal X chromosomes reveal the same telomere association for the inactive X but not for the active X chromosome. This nonlinear configuration is maintained during mitosis and in a murine environment.

Animals↗
PubMed1991

Hypogammaglobulinemia associated with cytomegalovirus pneumonia.

Transient but profound hypogammaglobulinemia occurred during cytomegalovirus (CMV) pneumonia in a patient who developed striking declines in number of T lymphocytes. A 66-year-old, female, human immunodeficiency virus-negative patient requiring long-term hemodialysis had normal serum immunoglobulin concentrations before the onset of CMV pneumonia (IgG, 1070-1470 mg/dl; IgA, 94-102 mg/dl; IgM, 30-48 mg/dl). During the pneumonia episode, serum immunoglobulin concentrations were profoundly reduced (IgG, 440 mg/dl; IgA, 40 mg/dl; IgM, 25 mg/dl). Total lymphocytes declined from 3048/mm3 to 212/mm3 with reductions in CD4+CD45- lymphocytes (inducers of B cells) to 9% (nl, 24%-32%) and CD4+CD45+ lymphocytes (inducers of suppressor T cells) to 4% (nl, 14%-22%). CD8 lymphocytes were reduced to 5% (nl, 19%-31%). As the pneumonia resolved, serum immunoglobulin concentrations returned to normal. This is one of the few reported instances of CMV infection apparently causing hypogammaglobulinemia.

Agammaglobulinemia↗
PubMed1990

Problems of instrument selection.

There are many problems in selecting appropriate instruments to use in research with children. Four problem areas have been outlined: instrument sensitivity, data source (adult report or observation v child self-report), adaptability to different ages and developmental levels, and the context or setting.

Child↗
PubMed1990

Erythema multiforme and Stevens-Johnson syndrome. Descriptive and therapeutic controversy.

Diagnosis and particularly the management of erythema multiforme and Stevens-Johnson syndrome are controversial in medical textbooks and thus in individual cases. In these diseases, fatalities may result from various causes, including secondary infection or visceral organ damage to lung, liver, or kidneys. We present a series of 13 cases managed by one group of physicians which demonstrates the controversy in certain cases, and we review the controversy in the medical literature. Corticosteroid therapy used in this series was considered beneficial in every case by the managing physician and lifesaving in some cases. There were no fatalities in this series. Although the summation may be considered as our opinion only, the frequently suggested "controlled trial of corticosteroid therapy" can probably never be done for ethical reasons, and series such as this will have to establish the standard of therapy.

Erythema Multiforme↗
PubMed1989

T cell function and expression are dramatically altered in T cell receptor V gamma 1.1J gamma 4C gamma 4 transgenic mice.

We have characterized transgenic mice carrying a functional T cell receptor (TCR) C gamma 4 (V gamma 1.1J gamma 4C gamma 4) gene. Results indicate that active transcription of the C gamma 4 transgene can influence expression of the endogenous C gamma 4, C gamma 1 (V gamma 3-, V gamma 4-, V gamma 2-, or V gamma 5J gamma 1C gamma 1) and C gamma 2 (V gamma 1.2J gamma 2C gamma 2) genes, while the ultimate expression of other TCR delta, alpha, and beta chain genes, as well as the adult T cell response, are relatively unaltered. Cells expressing transgenic C gamma 4 and endogenous delta TCR transcripts can migrate to the skin as dendritic epithelial cells (DEC) even though C gamma 4 cells are rarely, if at all, found in the skin. Transgenic and control mice were compared at 2 weeks, 6-7 weeks, and older. At 2 weeks, the thymus of transgenic mice, particularly the medulla, was much larger than control. Moreover, peripheral lymphoid tissues of younger mice were markedly (as much as 100-fold) more immunoreactive (both Con A response and alloreactivity). These differences, although persistent, became smaller in older mice. The data suggest that transgene expression has a major effect on T cell development and reactivity.

Animals↗