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C Walker

Publications and source records attributed to C Walker.

At least 127 records · Page 7Linked to original sources
PubMed1998

Genetic analysis of chromosomal rearrangements in the cyclops region of the zebrafish genome.

Genetic screens in zebrafish have provided mutations in hundreds of genes with essential functions in the developing embryo. To investigate the possible uses of chromosomal rearrangements in the analysis of these mutations, we genetically characterized three gamma-ray induced alleles of cyclops (cyc), a gene required for development of midline structures. We show that cyc maps near one end of Linkage Group 12 (LG 12) and that this region is involved in a reciprocal translocation with LG 2 in one gamma-ray induced mutation, cyc(b213). The translocated segments together cover approximately 5% of the genetic map, and we show that this rearrangement is useful for mapping cloned genes that reside in the affected chromosomal regions. The other two alleles, cyc(b16) and cyc(b229), have deletions in the distal region of LG 12. Interestingly, both of these mutations suppress recombination between genetic markers in LG 12, including markers at a distance from the deletion. This observation raises the possibility that these deletions affect a site required for meiotic recombination on the LG 12 chromosome. The cyc(b16) and cyc(b229) mutations may be useful for balancing other lethal mutations located in the distal region of LG 12. These results show that chromosomal rearrangements can provide useful resources for mapping and genetic analyses in zebrafish.

Alleles↗
PubMed1998

A randomized trial of mobilization of peripheral blood stem cells with cyclophosphamide, etoposide, and granulocyte colony-stimulating factor with or without cisplatin in patients with malignant lymphoma receiving high-dose chemotherapy.

The purpose of this study was to evaluate the addition of cisplatin to cyclophosphamide, etoposide, and granulocyte colony-stimulating factor (G-CSF) for the mobilization of peripheral blood stem cells (PBSC). Eighty-one patients with malignant lymphoma were randomized to receive either cyclophosphamide 4 g/m2 and etoposide 600 mg/m2 (CE), and G-CSF 6 microg/kg/day (n = 41), or the same drugs with cisplatin 105 mg/m2 (CEP; n = 40) followed by collection of PBSC. Seventy-eight of 81 patients (96%) had apheresis performed and 70 (86%) received high-dose chemotherapy (HDC) with PBSC support. The median number of CD34+ cells collected after CE was 19.77 compared with 9.39 x 10(6)/kg after CEP (p = 0.09). More patients receiving CEP had grade 3-4 gastrointestinal (p = 0.03) and neurologic toxicities (p = 0.05), had significant delays in recovery of neutrophils (p = 0.0001) and platelets (p = 0.009), and received more red blood cell (p = 0.03) and platelet (p = 0.08) transfusions than patients receiving CE. There were no significant differences in treatment-related deaths, relapse, survival, or event-free survival between patients receiving CE or CEP when all 81 patients or the 70 patients receiving HDC were evaluated. It was concluded that the addition of cisplatin to CE did not improve CD34+ cell yields, was associated with more morbidity and resource utilization, and was not associated with improvement in outcomes.

Adult↗
PubMed1998

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Humans↗
PubMed1998

Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia.

The cDNA coding for the transcriptional repressor protein Kid-1 was cloned in a screen for zinc finger proteins, which are regulated during renal development and after renal ischemia. Kid-1 mRNA levels increase in the course of postnatal renal development and decrease after acute renal injury caused by ischemia or administration of folic acid. We have raised a monoclonal anti-Kid-1 antibody and demonstrate that the Kid-1 protein is strongly expressed in the proximal tubule of the adult rat kidney. During nephron development, the Kid-1 protein appears after the S-shaped body stage concomitantly with the brush-border enzyme alkaline phosphatase. In two animal models of polycystic kidney disease, the expression of Kid-1 is downregulated. The loss of expression of Kid-1 in cyst wall cells correlates with the loss of alkaline phosphatase histochemical staining. Kid-1 mRNA levels are also reduced in rodent renal cell carcinomas, another condition characterized by epithelial cell dedifferentiation and increased proliferation. We propose that Kid-1 plays an important role during the differentiation of the proximal tubule.

Aging↗
PubMed1998

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for ecotoxicity.

There is growing public pressure to minimize the use of vertebrates in ecotoxicity testing; therefore, effective alternatives to toxicity tests causing suffering are being sought. This report discusses alternatives and differs in some respects from the reports of the other three groups because the primary concern is with harmful effects of chemicals at the level of population and above rather than with harmful effects upon individuals. It is concluded that progress toward the objective of minimizing testing that causes suffering would be served by the following initiatives--a clearer definition of goals and strategies when undertaking testing procedures; development of alternative assays, including in vitro test systems, that are based on new technology; development of nondestructive assays for vertebrates (e.g., biomarkers) that do not cause suffering; selection of most appropriate species, strains, and developmental stages for testing procedures (but no additional species for basic testing); better integrated and more flexible testing procedures incorporating biomarker responses, ecophysiological concepts, and ecological end points (progress in this direction depends upon expert judgment). In general, testing procedures could be made more realistic, taking into account problems with mixtures, and with volatile or insoluble chemicals.

Animal Testing Alternatives↗
PubMed1998

Low-level chromosome 12 amplification in a primary lipoma of the lung: evidence for a pathogenetic relationship with common adipose tissue tumors.

Cytogenetic analysis of a primary lipoma of the lung removed from a 56-year-old woman revealed the presence of a supernumerary marker chromosome in all metaphase cells analyzed; namely, 47,XX,+mar. To the best of our knowledge, this is the first cytogenetic description of a primary lipoma of lung. Genetic analysis of intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma have revealed the presence of one to three supernumerary ring or giant marker chromosomes composed of chromosome 12 segments as the characteristic anomaly. The marker chromosome in the present case was shown to be composed entirely of chromosome 12 material by subsequent analysis with a chromosome 12-specific paint probe and fluorescence in situ hybridization. Thus, analogous to intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma, extra chromosome 12 material is present. These findings support a pathogenetic relationship between this lipoma of unusual anatomic location and common adipose tissue tumors.

Chromosome Aberrations↗
PubMed1998

Allergic rhinitis history as a predictor of other future disqualifying otorhinolaryngological defects.

BACKGROUND: Problems with the otorhinolaryngological system represent the largest category of pilot referrals for specialist assessment and possible waiver recommendation in the U.S. Navy. Most of these referrals deal with allergic rhinitis (AR). Approximately 3% of all Naval aircrew have a waiver for AR. This paper tests the hypothesis that the identification of a history of AR is a predictor for the development of future disqualifying otorhinolaryngological (ear, nose, and throat, or ENT) diseases such as chronic sinusitis, alternobaric disease, conductive hearing loss, or the need for various surgical procedures (i.e., Caldwell Luc antrostomy, myringotomy, polypectomy, mastoidectomy, and functional endoscopic sinus surgery. METHODS: The U.S. Navy Aviation Medical Data Retrieval System (AMDRS) was searched for aircrew who were diagnosed only with AR in 1988. These aircrew were matched with a control group from the 1988 database who had no diagnoses of AR or any of the other disqualifying ENT diseases. The AR cohort and controls had their physical examinations up to 1995 assessed to see if any of the disqualifying ENT conditions had developed. RESULTS: There was a statistically significant increase in the number of identifiable chronic sinusitis cases but there was no significant relationship between an AR history and the development of any of the other ENT disease categories. CONCLUSION: Based on the study findings, it is doubtful that uncomplicated AR as an isolated historical diagnosis should be disqualifying for either candidate or designated aircrew.

Aerospace Medicine↗
PubMed1998

Ankle fractures in diabetics.

Ankle fractures are common and good results are expected. Insulin dependent diabetes mellitus is also common, and long-standing disease is associated with peripheral neuropathy. A trauma unit will inevitably receive patients with both problems. We describe two salutary lessons and suggest how our experience with diabetic neuroarthropathy might be avoided.

Ankle Injuries↗
PubMed1997

A Canadian hospital-based HIV/hepatitis C look-back notification program.

OBJECTIVE: To describe the process used to notify pediatric patients who received transfusions of blood or blood products at our institution before donor blood was routinely screened for antibodies to HIV (1985) and hepatitis C virus (1990), and to evaluate the effectiveness of the notification program. DESIGN: Patients who had received transfusions were identified through the hospital's medical records and the records from the Transfusion Medicine Laboratory. Patients were contacted by registered mail to provide notification of transfusion. A questionnaire was included with the notification to obtain information about the patient's awareness of the transfusion and whether he or she had undergone or planned to undergo testing for HIV and hepatitis C virus. SETTING: Tertiary care university-affiliated teaching hospital in Hamilton, Ont. PATIENTS: Patients 16 years of age or younger who had received blood products between February 1978 and November 1985. Patients who had received only albumin or immune serum globulin were not included as these products were not associated with viral transmission in Canada. RESULTS: Notification letters were sent to 1546 patients. Of these letters 522 (33.8%) were returned undelivered. Of the 1024 patients contacted 493 (48.1%) responded to the questionnaire, of whom 157 (31.8%) were not aware of their transfusion. A total of 130 (26.4%) of the respondents had already undergone testing for HIV, and 342 (69.4%) indicated that they would undergo such testing as a result of the notification. In contrast, only 30 (6.3%) of 474 respondents had undergone testing for hepatitis C virus, but 425 (89.7%) indicated that they would undergo such testing. Overall, the patients' response to the notification was neutral or positive; however, a number of patients expressed dissatisfaction and anxiety. CONCLUSIONS: The high proportion of patients who were unaware that they had undergone transfusion and who decided to undergo testing for HIV and hepatitis C virus as a result of notification supports the use of notification programs such as this one.

Adolescent↗
PubMed1997

Helicobacter pylori eradication using a 7-day regimen of low-dose clarithromycin, lansoprazole and amoxycillin.

AIM: To evaluate the efficacy of a 7-day regimen of clarithromycin 250 mg b.d., amoxycillin 1 g b.d., and lansoprazole 30 mg b.d. as a treatment for Helicobacter pylori infection. METHODS: H. pylori status of dyspeptic patients was assessed by 13C-urea breath test and at endoscopy by histology, culture and rapid urease testing of gastric biopsies. Fifty-one H. pylori-positive patients were treated with the above regimen. H. pylori status was reassessed by 13C-urea breath test not less than 28 days after completing treatment. Adverse events and compliance were evaluated. RESULTS: On an intention-to-treat basis. H. pylori infection was cured in 77% (95% CI: 65-88%) of patients. Minor side-effects including diarrhoea, nausea and taste disturbance were reported by 64% of patients. Ninety-five per cent of patients consumed > 95% of tablets. Metronidazole resistance was 29% but all cultures were sensitive to amoxycillin and clarithromycin. CONCLUSION: This 7-day treatment with low-dose clarithromycin was moderately effective in curing H. pylori infection. Although compliance was excellent, there was a high frequency of minor adverse events.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Weight changes and serum sodium concentrations after an ultradistance multisport triathlon.

OBJECTIVE: This study describes the incidence of hyponatremia and the weight changes during an ultradistance multisport triathlon. DESIGN: Descriptive research. SETTING: A 1-day triathlon in which each athlete kayaks 67 km, cycles 148 km, and runs 23.8 km. PARTICIPANTS: Forty-eight athletes competing in the race were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURES: All subjects were weighed before the race and on completion of the race. A blood sample for serum sodium was taken at the finish of the race. RESULTS: The mean weight change over the course of the race was a loss of 2.5 kg (SD +/- 1.7, n = 48), or a mean percentage loss of body weight of 3.1% (SD +/- 2.07). This was highly statistically significant (p < 0.0001) using the Student paired t test. No athletes gained weight, and six athletes maintained their same weight. Only one athlete was hyponatremic (Na = 134 mEq/L). This athlete maintained his weight over the course of the race and he did not seek medical attention. The mean serum sodium concentration at the end of the race was 139.3 mEq/L (SD = 2.28, n = 47). There was a significant correlation (r = 0.30, p = 0.04) between sodium levels and weight change during the race: the greater the weight loss, the higher the serum sodium concentration. There was no significant correlation between the degree of weight loss and athletes' finishing times (r = 0.11, p = 0.45). CONCLUSIONS: Symptomatic hyponatremia did not occur in the 1996 Coast to Coast multisport triathlon, although one athlete had borderline hyponatremia. Athletes lose significant amounts of weight over the course of this multisport event, but nevertheless manage to complete the race.

Adult↗
PubMed1997

The pathogenesis of ED71, a defined deletion mutant of equine herpesvirus-1, in a murine intranasal infection model for equine abortion.

A series of mutants of equine herpesvirus-1 (EHV-1) which contain deletions in non-essential genes was previously characterized in a murine intranasal infection model. One mutant, ED71 which was shown to be attenuated in the model, was further characterized by inoculation into pregnant mice. Despite the attenuation previously reported, intranasal inoculation of pregnant mice resulted in premature parturition and the birth of dead or dying foetuses. Furthermore, mice inoculated before pregnancy with the same mutant, and subsequently challenged 14 days after conception with wild-type virus, were not protected from abortion.

Abortion, Veterinary↗
PubMed1997

Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

Adult↗
PubMed1997

Evidence for genetic control of changes in f-actin polymerization caused by pathogenic microorganisms: in vitro assessment using gingival fibroblasts from human twins.

Attachment to and migration upon a substratum, as well as other functions of connective tissue cells, are regulated mainly by cytoplasmic structural proteins, particularly filamentous actin (f-actin). Pathogenic microorganisms exert negative effects on cytoskeletal proteins. In the present study, normal gingival fibroblasts from 10 sets of human twins (6 fraternal, DZ; 4 identical, MZ) were exposed to soluble extracts from Porphyromonas gingivalis or Fusobacterium nucleatum, then f-actin was stained using FITC-labeled phalloidin. Cells were examined under fluorescence, and a computer-assisted image analyzer quantitated f-actin polymerization as fluorescence intensity on a per-cell basis. Intraclass correlation coefficients for f-actin in MZ/MZ vis-a-vis DZ/DZ paired cell cultures were determined to assess the possible heritability of responses to the microorganism preparations. F-actin labeling was significantly different between control cultures and those exposed to the extracts. Both F. nucleatum and P. gingivalis effected f-actin and fibroblast morphology. When the data were adjusted for gender and age effects, and for differences in control f-actin levels, fibroblasts from MZ twin pairs were moderately similar in both absolute and relative responses to bacterial challenges; cells from DZ twins showed little similarity when response was measured on the absolute scale, and moderate similarity using the relative scale.

Actins↗
PubMed1997

Restriction Analysis of PCR-Amplified Internal Transcribed Spacers of Ribosomal DNA as a Tool for Species Identification in Different Genera of the Order Glomales.

A technique combining PCR and restriction fragment length polymorphism analysis was used to generate specific DNA fragment patterns from spore extracts of arbuscular mycorrhizal fungi. With the universal primers ITS1 and ITS4, DNA fragments were amplified from species of Scutellospora and Gigaspora that were approximately 500 bp long. The apparent lengths of the corresponding fragments from Glomus spp. varied between 580 and 600 bp. Within the genus Glomus, the restriction enzymes MboI, HinfI, and TaqI were useful for distinguishing species. Depending on the restriction enzyme used, groups of species with common fragment patterns could be found. Five tropical and subtropical isolates identified as Glomus manihotis and G. clarum could not be distinguished by their restriction patterns, corresponding to the morphological similarity of the spores. The variation of internal transcribed spacer sequences among the Gigaspora species under study was low. Fragment patterns of Scutellospora spp. showed their phylogenetic relationship with Gigaspora and revealed only a slightly higher degree of variation.

Journal Article↗
PubMed1997

Regulation of apoptosis in uterine leiomyomata.

Tumors developing from hormone-dependent tissues, such as the breast and prostate, have been successfully treated in the clinic by methods of hormone ablation, and the resulting tumor regression has been shown to occur at least in part by the process of apoptosis. The growth of leiomyomas arising from uterine smooth muscle cells is similarly modulated by circulating steroid hormones and has been associated with periods of increased estrogen secretion. The inhibition of ovarian hormone production by endocrine therapy often results in the regression of these tumors, but the role of apoptosis in this process has not been elucidated. Using cell lines derived from the Eker rat model of uterine leiomyoma, we have investigated the mechanism of growth inhibition by estrogen deprivation. Estrogen-depleted medium and the antiestrogen tamoxifen significantly reduced cell numbers in culture and arrested cell proliferation, but did not induce apoptosis. However, the presence of an intact apoptotic pathway was demonstrated in these cells by serum starvation. In vivo data were in agreement with in vitro results, which showed that tamoxifen treatment does not change the apoptotic rate of leiomyoma tissues. Therefore, growth modulation of leiomyomas by hormone deprivation occurs via mechanisms independent of apoptosis, indicating a fundamental difference in the response of leiomyomas to hormone deprivation from that of tumors of the breast and prostate. These data suggest that creation of a hypoestrogenic milieu within leiomyomas reduces tumor volume without inducing a concomitant increase in the rate of apoptosis, which may be responsible for the limited effectiveness of currently available medicinal therapies.

Animals↗