Search PubMed⌕ Search

Biomedical subjects

J A Ross

Publications and source records attributed to J A Ross.

At least 19 recordsLinked to original sources
PubMed1999

Genomic imprinting of H19 and insulin-like growth factor-2 in pediatric germ cell tumors.

BACKGROUND: Insulin-like growth factor-2 (IGF2) and H19 are reciprocally imprinted genes on chromosome 11; IGF2 is expressed paternally and H19 is expressed maternally. Loss of imprinting (LOI) at both H19 and IGF2 has been reported in seven fully informative adult testicular germ cell tumors (GCTs) and may contribute to germ cell carcinogenesis. METHODS: Genomic DNA from 61 pediatric GCTs was amplified by polymerase chain reaction (PCR) and screened for heterozygosity at both IGF2 and H19 using either ApaI or RsaI, respectively. If heterozygous, polyadenylated RNA was isolated and reversed-transcribed into cDNA. cDNA then was amplified by PCR and the products were digested with restriction enzymes to evaluate GCT expression of IGF2 and H19. RESULTS: Eleven pediatric GCTs were fully informative for H19 and IGF2, including 5 ovarian GCTs, 2 testicular GCTs, and 4 extragonadal GCTs. Consistent with prior studies, both testicular GCTs showed LOI at both H19 and IGF2. In contrast, three of the five ovarian GCTs had LOI at both IGF2 and H19; one had LOI at IGF2 only, and one retained imprinting at both loci. Only one of the four extragonadal GCTs had LOI at IGF2 whereas three of the four had LOI at H19. CONCLUSIONS: These data suggest that LOI at H19 and IGF2 also may be common in pediatric testicular GCTs. However, ovarian and extragonadal pediatric GCTs showed variable patterns of LOI that may indicate differences in the timing of carcinogenesis in germ cells at these sites.

Adolescent↗
PubMed1999

Polycyclic aromatic hydrocarbons: correlations between DNA adducts and ras oncogene mutations.

This review describes a series of studies on the tumorigenic activities of polycyclic aromatic hydrocarbons (PAHs) in various experimental animal model systems, their abilities to form PAH-DNA adducts in target tissues, and their abilities to mutate ras oncogenes in PAH-induced tumors. The review is limited to those PAHs that do not contain nitrogen, for which ras mutations have been detected in induced tumors, and for which some information is available about the structures of the DNA adducts induced in the target tissue. In general, PAHs that form DNA adducts at deoxyadenosine induce mutations at codon 61, whereas those PAHs that form DNA adducts at deoxyguanosine primarily induce mutations at codons 12 or 13. Those PAHs that induce adducts at both bases induce both types of mutations. These correlations provide evidence for the involvement of adduct-directed mutations in ras in the etiology of these tumors. The induced mutation spectra in ras may in fact point back to the identity of the type of adduct formed.

Animals↗
PubMed1999

Epidemiologic studies of childhood leukemia: where do we go from here?

Much of our knowledge of the mechanisms of carcinogenesis has resulted from the study of rare cancers, including retinoblastoma, angiosarcoma, and vaginal clear cell carcinoma. Due to the heterogeneity of childhood leukemia, epidemiologic studies that focus on children with unique clinical and genetic manifestations of the disease could potentially lead to further understanding of leukemogenesis.

Acute Disease↗
PubMed1999

Pancreatic cancer as a model: inflammatory mediators, acute-phase response, and cancer cachexia.

Patients with pancreatic cancer frequently develop the syndrome of cancer cachexia. Pro-inflammatory cytokines have been strongly implicated in the pathogenesis of this syndrome. In patients with pancreatic cancer an acute-phase response (an index of pro-inflammatory cytokine activity) is associated with accelerated weight loss, hypermetabolism, anorexia, and a shortened duration of survival. However, little is known about the primary significance of the acute-phase response in terms of altered hepatic export protein synthesis rates and its potential impact on the body's nitrogen economy. In a recent series of studies on weight-losing pancreatic cancer patients with hypoalbuminemia we have demonstrated albumin synthesis to be unaltered whereas fibrinogen synthesis is increased two- to threefold compared with healthy controls. Because of the mismatch in amino acid composition between the body's main labile amino acid reserve (skeletal muscle) and that of acute-phase proteins, these results lend support to the concept that in pancreatic cancer the reprioritization of body protein metabolism during an acute-phase response may well be a significant factor in the loss of lean tissue in these patients.

Acute-Phase Proteins↗
PubMed1999

The effectiveness of non-surgical management of early interstitial pregnancy: a report of ten cases and review of the literature.

OBJECTIVE: To assess the effectiveness of non-surgical management of interstitial pregnancy. DESIGN: A prospective interventional study. SUBJECTS: Eleven women with the ultrasound diagnosis of interstitial ectopic pregnancy. METHODS: Women with suspected early pregnancy complications were examined by transvaginal ultrasound. Those with the diagnosis of interstitial pregnancy were offered non-surgical treatment with methotrexate, which was administered systemically or by local injection. Follow-up with regular measurements of beta-human chorionic gonadotropin and ultrasound scans continued until the pregnancy had resolved completely. RESULTS: Ten women were managed non-surgically, and one woman opted for surgery. Five women received systemic and five local methotrexate. Local therapy was successful in all five cases (100%), whereas four out of five (80%) women receiving systemic methotrexate were cured. Significant side-effects were noted in two women following systemic therapy. In comparison, there were no side-effects in the group of women who received local therapy. There were no significant differences between the two treatment groups in the length of time taken for the pregnancy to resolve. CONCLUSIONS: Non-surgical treatment of interstitial pregnancy with methotrexate appears to be safe and effective. Local administration appears to be more successful and better tolerated by patients and may be used as the first-line therapy.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer.

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients.

Acute-Phase Proteins↗
PubMed1999

The causes of acute leukemia.

Although impressive biologic advances have increased understanding of leukemogenesis, we know little about the causes of the acute leukemias. Epidemiologic studies have focused primarily on children. Higher birth weight is associated with an increased risk of childhood acute leukemia. Several theories have been advanced that may account for these observations, and additional biologic studies are needed. Some epidemiologic studies suggest that the acute leukemias in children may have an infectious component. Again, further work, especially in the area of specific causative agents, is necessary. Another area for future epidemiologic study includes investigation of exposure to natural and synthetic DNA topoisomerase II inhibitors. Preliminary evidence suggests that exposure to these agents, which are found in certain foods and medications, may be related to the subsequent development of acute leukemia in infants.

Acute Disease↗
PubMed1999

The anti-catabolic effects of n-3 fatty acids.

The reversal of catabolic processes remains a significant challenge, partly related to the complexity of such processes and our incomplete understanding of the mechanisms involved. The n-3 fatty acids may be able to attenuate catabolism. This review examines the potential sites of action for these fatty acids and the evidence that supports their anti-catabolic properties.

Animals↗
PubMed1999

Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer.

The level of the acute-phase response is a major predictor of survival in patients with advanced pancreatic cancer. This study examines the association between the acute-phase protein response, as determined by serum C-reactive protein, and serum levels of interleukin-6, soluble interleukin-6 receptor and the soluble tumour necrosis factor receptors in patients with pancreatic cancer. Thirty-four blood samples were collected from 13 patients with advanced pancreatic cancer. Samples were also collected from six healthy subjects. Levels of C-reactive protein, interleukin-6, soluble interleukin-6 receptor and soluble tumour necrosis factor receptors 55 and 75 were measured by indirect ELISA. Serum levels of C-reactive protein, interleukin-6 and soluble tumour necrosis factor receptors 55 and 75 were significantly higher in cancer patients than in controls. Levels of serum soluble interleukin-6 receptor were not significantly different between the two groups. In cancer patients, a significant positive association was found between the level of the acute-phase protein response and serum levels of interleukin-6, soluble tumour necrosis factor receptor 55 and soluble tumour necrosis factor receptor 75. No association was found between levels of soluble interleukin-6 receptor and any other factor. There is no significant relationship between the level of soluble interleukin-6 receptor and the acute-phase protein response in vivo and the biological role of soluble interleukin-6 receptor in the chronic inflammatory component of cachexia remains unclear.

Acute-Phase Reaction↗
PubMed1998

Hepatoblastoma incidence in the United States from 1973 to 1992.

BACKGROUND: There is recent evidence to suggest that extremely low birth weight is associated with the occurrence of hepatoblastoma. PROCEDURE: In light of this possibility, we evaluated trends in hepatoblastoma incidence in the United States among children age 4 years and younger. RESULTS: We found an increasing trend (5.2%) in hepatoblastoma incidence over the past two decades, a period that corresponds with improved survival of very low birth weight children. CONCLUSION: Future studies of hepatoblastoma that incorporate birth weight are appropriate.

Child, Preschool↗