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Biomedical subjects

N Fox

Publications and source records attributed to N Fox.

At least 55 records · Page 3Linked to original sources
PubMed1992

Hibernoma formation in transgenic mice and isolation of a brown adipocyte cell line expressing the uncoupling protein gene.

Transgenic mice were produced containing the adipocyte-specific regulatory region from the adipocyte P2 (aP2) gene linked to the simian virus 40 transforming genes. Most of the transgenic mice developed brown fat tumors (hibernomas) in their interscapular brown adipose tissue. Hibernoma formation was noticeable in some of the mice as early as 1 day after birth and most of the mice developed very large tumors by 1 month of age. All of the tumor tissue expressed the brown fat-specific uncoupling protein (UCP) gene as well as the aP2 gene. Several of the tumors have been used to establish cultured cell lines and at least one of these lines can be induced to differentiate into brown adipocytes. The cultured adipocytes express mRNA for UCP upon stimulation with N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, norepinephrine, isoproterenol or D7114, a beta 3 adrenergic agonist. Thus, regulation of the key thermogenic gene UCP can now be studied in an established cell line.

Adipose Tissue, Brown↗
PubMed1991

The cost of hospitalization for the late complications of diabetes in the United States.

Estimates of the cost of diabetes should take into account the development of complications. Patient records identified from the 1987 National Hospital Discharge Survey were used to evaluate the risk of hospitalization due to late complications. Hospitalization for diabetic nephropathy reached a peak of 6.74/1000 between the ages of 45 and 54 years, compared to 0.14 to 1.80/1000 in controls. Diabetic patients less than or equal to 45 years of age were 46 times more likely to be hospitalized due to neuropathy. The risk of cardiovascular complications is high, with a greater incidence of arterial than venous disorders. Diabetic patients were 22 times more likely to be admitted for skin ulcers/gangrene, 15 times more likely due to peripheral vascular disease, and 10 times due to atherosclerosis. The risk of cerebrovascular accident and heart disease was 6 to 10 times greater in diabetic patients. Seventy-five per cent of diabetic cardiovascular disorders are myocardial infarction or chronic ischaemia. Hospitalization from renal complications occurs at younger ages than in the general population. Ophthalmic complications increase with age. Diabetic complications account for 2% of the total hospital admissions in the US in 1987. The total cost of the treatment of late diabetic complications was estimated at +5091 million (cardiovascular 74%; renal diseases 10%; nephropathy 3.6%; ophthalmic disorders 1.5%; other unspecified diseases 10%).

Age Factors↗
PubMed1990

Predicting IQ change in preschoolers with developmental delays.

This study examined IQ change over a 2-year period in 291 young children (mean age 39 months) referred to a pediatric developmental clinic for evaluation of developmental problems. Although correlation between initial and follow-up IQ was very high (0.78), there was also a significant increase in mean IQ score, from 67.12 to 74.06. Moreover, 26% of the subjects showed IQ increase of 16 points or more. Variables making some contribution to IQ change were initial clinical diagnosis, etiology, and intervention. Children diagnosed with a developmental language disorder made significantly greater gains than those diagnosed as mentally retarded. Sex, family status, initial age, and test interval were not significantly correlated with IQ change. We concluded that prediction for individual children is difficult, but that initial diagnosis may be useful in differentially predicting IQ change in young children with developmental delays.

Affective Symptoms↗
PubMed1990

Osteosarcomas in transgenic mice expressing an alpha-amylase-SV40 T-antigen hybrid gene.

Mice of a transgenic mouse lineage 501, produced by zygotic injection of the parotid alpha-amylase promoter-SV40 T-antigen hybrid gene, developed osteosarcomas at about 15 months of age. The tumors predominantly involved the axial skeleton, were sometimes multiple, and metastasized to the liver. A cell line derived from a primary tumor produced osteosarcomas on transfer to nude mice. The 501 transgenic lineage thus provides a valuable new model for studying the histogenesis of osteosarcomas.

Animals↗
PubMed1989

Metastatic hibernomas in transgenic mice expressing an alpha-amylase-SV40 T antigen hybrid gene.

Mice transgenic for a hybrid gene containing the liver promoter of the mouse amylase gene (Amy-1a) fused to the SV40 tumor antigen coding region unexpected developed malignant brown adipose tissue tumors (malignant hibernomas). Expression of the alpha-amylase gene had previously been thought to be confined to the liver parotid, and pancreas; however, analysis of white and brown adipose tissue from nontransgenic mice revealed expression of the endogenous Amy-1a gene in these tissues. Gene constructs driven by the Amy-1a liver promoter thus provide a means of targeting gene expression to the adipocyte cell lineage in transgenic mice. Moreover the high frequency of metastases in the liver, lungs, spleen, heart, and adrenals of these mice provides an experimental system in which to study the development of disseminated malignancy.

Adipose Tissue↗
PubMed1988

The direct medical costs of osteoporosis for American women aged 45 and older, 1986.

Annual direct medical costs of osteoporosis incurred by American women aged 45 and older are estimated at $5.2 billion in 1986. Costs are stratified by type of care (inpatient hospital, nursing home and outpatient) and by age group (ages 45 to 59, 60 to 74 and 75 and older). Survey data from the National Center for Health Statistics are combined with census data to project utilization estimates from the survey years to 1986. A portion of all health care encounters for diagnoses secondary to osteoporosis are considered to be caused by osteoporosis according to age- and diagnosis-specific attribution weights. These weights are derived from the opinion of a panel of osteoporosis experts. For inpatient hospitalization, the assigned diagnosis related group (DRG) is used to further specify osteoporosis as the cause of hospitalization. The cost components of osteoporosis care for American women in 1986 are inpatient care, $2.8 billion; nursing home care, $2.1 billion; and outpatient care, $0.2 billion. Study results suggest considerable potential future cost-savings of osteoporosis prevention and abatement.

Age Factors↗
PubMed1988

The cost-effectiveness of maintenance therapy for duodenal ulceration with an H2-antagonist.

Data from several sources are used to quantify the expected direct medical costs of a recently healed duodenal ulcer patient prescribed an H2-antagonist (famotidine) for a 6-month period. These costs are compared to the expected direct medical costs associated with not using maintenance therapy. Our results indicate that the estimated direct cost of patients prescribed a 6-month regimen of an H2-antagonist (famotidine) is 30.3% lower than patients who receive no H2-antagonist therapy. Most of the savings result from a reduced risk of hospitalization and surgery. The results of the sensitivity analysis of four varying scenarios indicate that H2-antagonist maintenance therapy remains less costly even when the assumptions underlying the model are varied enormously. We conclude that the decision to withhold maintenance therapy with H2-antagonists should not be based on economics.

Cost-Benefit Analysis↗
PubMed1988

Expression and regulation of the pituitary- and placenta-specific human glycoprotein hormone alpha-subunit gene is restricted to the pituitary in transgenic mice.

Expression of the glycoprotein hormone alpha subunit occurs in both the pituitary and placenta in humans. However, this study found that expression of this subunit is restricted to the pituitary in mice. An interspecies analysis of human alpha-subunit gene regulation was undertaken, using the transgenic-mouse approach. In mice transgenic for a genomic clone containing the complete human alpha-subunit gene and several kilobases of 5'- and 3'-flanking sequences, cell-type-specific expression and hormonal regulation of the human alpha-subunit transgene occurred in the mouse pituitary, whereas no expression of the transgene was detectable in the mouse placenta. These findings provide strong evidence that a common trans-acting factor(s) regulates glycoprotein hormone alpha-subunit gene expression in the human and mouse pituitaries; however, this factor(s) or a unique factor(s), though functional in the human placenta, is either nonfunctional or absent in the mouse placenta.

Animals↗
PubMed1987

Azlocillin, cephalothin, and tobramycin therapy in febrile solid tumor patients with chemotherapy-induced leukopenia.

Although the semisynthetic broad-spectrum acylureido-penicillin, azlocillin has been demonstrated to have significant antibiotic activity in leukemic patients, its role in combination therapy of febrile granulocytopenic patients with chemotherapy-treated solid tumors has not been clearly delineated. Thirty-five solid tumor patients with chemotherapy-induced absolute granulocytopenia (less than 1000 granulocytes/ml) associated with fever (greater than 38.3 degrees C) were treated on a prospective study with a combination of azlocillin 4 g intravenously (IV) every 6 hours, cephalothin 2 g IV every 6 hours, and tobramycin 80 to 100 mg IV every 8 to 12 hours. Prior chemotherapy included doxorubicin combinations in 18 patients and other combinations in 17 patients. Granulocyte counts preantibiotic therapy were greater than 100 granulocyte/ml in 14 patients, 100 to 499 in nine patients, and 500 to 1000 in 12 patients. Granulocyte nadirs were less than 100 in 20 patients, 100 to 499 in nine patients, and 500 to 1000 in six patients. Times for granulocytes to rise towards normal were 1 to 3 days in eight patients, 4 to 6 days in 18 patients, and 7 or more days in nine patients. Tobramycin levels were primarily in the peak range of 3 to 6 micrograms/ml and trough range of 0 to 1.9 micrograms/ml. The site and pathogen were identified in nine patients, the infection site clinically documented without isolated pathogen in three patients, and no site or pathogen identified in 23 patients. Of the 35 patients, 34 had good responses to the antibiotic combination (complete disappearance of fever and other evidence of infection). Serum creatinine rose 0.4 to 0.6 mg/dl in nine patients, 0.7 to 1.5 in four patients, and 1.5 in one patient (obstructive uropathy). The only other noted antibiotic-related side effect was hypokalemia. This antibiotic combination had little toxicity with marked efficacy.

Adult↗
PubMed1987

Expression and cAMP-mediated regulation of the human gonadotropin alpha subunit gene in transfected mouse L-cells.

Expression of the dimeric glycoprotein hormone, human chorionic gonadotropin (HCG), occurs either eutopically in placental trophoblast cells and trophoblastic tumor cells (choriocarcinoma) or ectopically in nontrophoblastic tumor cells. However, regulation of constitutive HCG-subunit mRNA production appears to differ in trophoblastic and nontrophoblastic cells, as evidenced by the fact that cAMP analogs and agonists enhance eutopic but not ectopic HCG-subunit mRNA synthesis. In the present study, we compared the effects of cAMP on HCG alpha-subunit expression in human choriocarcinoma cells and in nontrophoblastic mouse L-cells stably transfected with the HCG alpha-subunit gene. Constitutive levels of alpha-subunit expression in transfected mouse L-cells were equivalent to or exceeded those found in choriocarcinoma cells as determined by Northern blot analysis and indirect immunofluorescence for alpha-subunit protein. However, cAMP-mediated induction of alpha-subunit gene expression was retained in nontrophoblastic L-cells and closely paralleled that observed in human choriocarcinoma cells. These findings indicate that cells distinctly nontrophoblastic in origin may share the necessary cellular factors for cAMP-mediated induction of alpha-subunit gene expression. Failure of ectopic HCG-producing tumor cells to be stimulated by cAMP may thus be the result of deletion or mutation of such factors.

Animals↗
PubMed1986

Moderate alcohol consumption and primary cardiac arrest.

To determine if light to moderate consumption of alcohol influences the risk of primary cardiac arrest, the authors investigated 152 cases, 25-75 years of age, without prior heart disease or co-morbidity, in whom a primary cardiac arrest occurred during a 14-month period in King County, Washington state, December 1979-January 1981. Spouses of cases and those of 152 demographically similar residents of King County were interviewed to quantify average alcohol consumption over the prior year for beer, wine, and spirits combined. After adjustment for hypertension, smoking, and physical activity, light to moderate alcohol consumption was associated with a reduced risk of primary cardiac arrest. Compared to persons who were nondrinkers (less than 1 drink/month), the estimated relative risk for light drinkers (greater than or equal to 1 drink/month but less than 1 drink/day) was 0.7 (95% confidence interval, 0.5-1.0), and for moderate drinkers (1-3 drinks/day), 0.5 (95% confidence interval, 0.3-1.0). These data are consistent with the hypothesis that light to moderate alcohol consumption reduces the risk of primary cardiac arrest.

Adult↗
PubMed1984

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients.

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1983

Male murine embryonal carcinoma cell line selectively metastatic to the ovaries and adrenals.

Developmentally pluripotent embryonal carcinoma cells were isolated from chromosomally male embryo-derived teratocarcinoma and adapted to in vitro growth without a feeder layer. The uncloned original cell line as well as clones derived from it have a tendency to selectively localize to the ovaries and adrenals upon intravenous injection into adult female mice, but only to the adrenals when injected into male mice. The overall take of injected tumor cells was lower in males and the tumors formed slower in males than in females. These findings suggest that the growth of this karyotypically male embryonal carcinoma could be under hormonal regulation.

Adrenal Gland Neoplasms↗
PubMed1983

The effects of regional factors on the growth rate and the differentiation of mouse teratocarcinoma.

Murine embryonal carcinoma cells, the pluripotent stem cells of teratocarcinoma were injected simultaneously into caudal and cranial sites on the back of syngeneic recipients in order to determine whether regional anatomical differences affect their take and growth rate and differentiation. The overall tumour take rate was higher in caudal than cranial sites, but the initial weight of tumours was higher in the cranial than caudal sites. Tumours developing in the two anatomical sites grew at the same rate with a linear increase in volume. At the end of the 4-week experimental period the differences in the size of anterior and posterior tumours were negligible and no histological differences were noted between the two groups. Our data indicate that regional factors significantly affect the take rate and the initial growth of this murine teratocarcinoma, i.e. the establishment of solid tumours from injected stem cells. The growth rate of established tumours was not affected by regional factors.

Animals↗