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Biomedical subjects

D A Swartz

Publications and source records attributed to D A Swartz.

12 recordsLinked to original sources

Lipid level and type alter stearoyl CoA desaturase mRNA abundance differently in mice with distinct susceptibilities to diet-influenced diseases.

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity.

Animals↗

The e subunit gene of murine F1F0-ATP synthase. Genomic sequence, chromosomal mapping, and diet regulation.

Genomic sequences encoding murine Lfm1, whose predicted protein sequence is 96% and 98% similar to bovine and rat F1F0-ATP synthase e subunits (respectively), have been amplified from BALB/cByJ DNA, cloned, and sequenced. The 1.1-kilobase gene has 3 introns and 4 exons, and its coding sequence differs by two nucleotides compared to the previously published BALB/cHnn Lfm1 cDNA sequence. A PstI restriction site polymorphism in intron 2 between C57BL/6J and Mus spretus was used to map this gene to Chromosome 5 near D5Mit9. Related sequences were mapped on Chromosomes 8, 11, and 2 unlinked loci on Chromosome 2 using Southern blot analyses with the 1. 1-kilobase gene as probe. Previous studies from this laboratory indicated that the Lfm1/e subunit was regulated by the level of dietary fat and carbohydrate. Northern hybridization analyses demonstrated that e subunit mRNA abundance showed statistically significant differences (p < 0.025) between hearts of BALB/c mice fed 3% and those fed 20% corn oil for 2 weeks and in liver (p < 0. 05) from the same animals. Significant differences were also observed in hepatic and heart mRNA expression at different times after eating in animals subjected to a fast/refeed regimen. The implications of the high degree of sequence similarity to the e subunit for rat and bovine F1F0-ATP synthase and its regulation by diet are discussed.

Animals↗

Temporal-regulation of serum lipids and stearoyl CoA desaturase and lipoprotein lipase mRNA in BALB/cHnn mice.

Databases for genes expressed in humans or cell cultures are being developed as a part of the Human Genome Project. Because genomes respond to nutritional and other environmental variables, quantitative analyses of mRNA abundance under defined nutritional and physiological states are required to understand normal metabolism and to clarify differences between normal and disease phenotypes. Reported here are comparisons of food intake, growthp5erum lipids and expression of mRNA for hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in female BALB/cHnn mice following food deprivation and refeeding at the end of 2 wk of feeding semipurified diets with 3, 10 or 20% corn oils. Body weights and utilization of dietary energy were similar for mice fed all three diets. There were no differences in serum lipid concentrations associated with the level of dietary fat during subsequent food deprivation and refeeding, but significant differences in serum triglycerides and total serum cholesterol were observed between food-deprived and fed mice. Heart lipoprotein lipase and hepatic Scd1 mRNA expression levels were affected significantly by concentration of corn oil and by time after eating. These and other studies examining gene regulation by dietary variables and nutrient availability are discussed in relation to development of diet-regulated gene databases for laboratory animals fed semipurified diets.

Animals↗

F1Fo-ATPase subunit e gene isolated in a screen for diet regulated genes.

Described is a protocol for isolating genes differentially regulated by the level of an essential nutrient in the diet. One gene, designated LFM-1 (Low Fat Mammary), was identified by subtractive hybridization and plus/minus screening in a lambda-cDNA library constructed with mRNA from mammary glands of virgin, tumor-free Balb/c mice fed a low fat diet; a second gene, stearoyl CoA desaturase, known to be regulated by the level of fat intake, was also isolated. The procedure can be modified for use with other constituents. The differential expression of LFM-1 was noted in mammary glands, liver, and kidney but not other tissues of mice fed low fat compared to high fat. LFM-1 is 86% identical to the gene encoding the e subunit of bovine F1-Fo ATPase and 89% identical to an UV-light induced gene (DDIU4) from Chinese hamster fibroblasts. Differential hybridization analyses indicated that LFM-1 may belong to a gene family.

Amino Acid Sequence↗

Induction of differentiation of human promyelocytic leukemia cell line HL-60 by retinoyl glucuronide, a biologically active metabolite of vitamin A.

We examined the differentiation activity of retinoyl beta-D-glucuronide, a biologically active physiological metabolite of vitamin A, using the human promyelocytic leukemic cell line HL-60, which can be induced to differentiate with retinoic acid. Retinoyl beta-D-glucuronide (1 microM) inhibited HL-60 cell proliferation by 55-75%, inhibited tritiated thymidine incorporation into DNA by 63-80%, and induced 38-50% of the cells to differentiate into mature granulocytes. The potency of growth inhibition and induction of differentiation by retinoyl beta-D-glucuronide was similar to that of all-trans-retinoic acid. The continuous presence of either retinoyl beta-D-glucuronide or all-trans-retinoic acid was not required to obtain maximum growth arrest and differentiation: a 1-hr exposure of HL-60 cells to the retinoids gave the same response (measured after a total incubation time of 48 hr) as a 24-hr or 48-hr continuous treatment. Retinoyl beta-D-glucuronide (0.1-0.2 mM) was 50% less cytotoxic to HL-60 cells than all-trans-retinoic acid at an equimolar concentration. Retinoyl beta-D-glucuronide was not significantly metabolized to other retinoids; retinoic acid was not formed during incubation. We conclude that retinoyl beta-D-glucuronide can arrest HL-60 cell proliferation and induce their differentiation into mature granulocytes; it may act by itself or by being hydrolyzed to retinoic acid, which could be immediately utilized and metabolized. The therapeutic use of this retinoid as an antineoplastic agent is suggested.

Cell Differentiation↗

Bladder leiomyosarcoma: a review of 10 cases with 5-year followup.

Of 10 patients with leiomyosarcoma of the bladder followed for a minimum of 5 years 4 remain free of disease at 5, 6, 6 and 9 years, respectively, following partial cystectomy. An additional patient who was treated sequentially by radiation, radical cystectomy and chemoimmunotherapy survived for 10 years before death of metastatic disease. Wide surgical extirpation (partial or radical cystectomy) remains the curative treatment of choice.

Adult↗

Should an elevated human chorionic gonadotropin titer alter therapy for seminoma?

We reviewed the clinical courses of 55 patients with pure seminoma of the testis to determine the influence of elevated levels of beta-human chorionic gonadotropin on prognosis. Of 44 patients with stage I and 11 with stage IIA seminomas 42 and 36 per cent, respectively, had elevated gonadotropin levels after orchiectomy and before radiotherapy. At followup, ranging from 12 to 64 months, 54 patients (98 per cent) were free of disease. We concluded that an elevated gonadotropin level after orchiectomy is not a significant prognostic indicator and that these patients should be treated with standard radiotherapy techniques.

Adult↗

Fine needle aspiration cytology of papillary endometrioid carcinoma of the prostate. The grooved nucleus as a cytologic marker.

The fine needle aspiration (FNA) cytologic findings of an endometrioid carcinoma of the prostate are presented, along with the histologic, immunohistochemical and endoscopic features. Cystoscopy of an elderly male patient with hematuria and symptoms of bladder outlet obstruction showed the delicate papillary growths at the verumontanum that are characteristic of this lesion. Transrectal FNA of the prostate produced samples that included clusters of malignant cells with crowding and overlapping of hyperchromatic nuclei containing prominent nucleoli and a loss of polarization and cohesion. Many of the groups of tumor cells suggested papillary structures. A novel finding in the aspirate was a grooved nucleus in 10% of the tumor cells. Immunohistochemical staining of biopsy sections of the papillary growths for prostate-specific antigen was strongly positive. It is important to recognize this variant of prostatic carcinoma since its behavior and response to therapy are not yet established.

Adenocarcinoma↗