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Biomedical subjects

E Bowen

Publications and source records attributed to E Bowen.

13 recordsLinked to original sources

Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2.

The ratio of CD4 T cells to CD8 T cells (CD4:CD8 ratio) varies over two-fold between C57BL/6 and DBA/2 mice for both T cell precursors in the thymus and mature T cells in the periphery. Correlation analysis of the CD4:CD8 ratio in thymic precursors vs peripheral T cells in F2 and backcross mice found that thymic precursor ratios are inherited independently from those in the periphery, indicating that the CD4:CD8 ratios in these populations are affected by distinct genetic mechanisms. A genome scan of progeny in the phenotypic extremes identified three quantitative trait loci (QTLs). Trmq1 (for T cell ratio modifier QTL 1) was detected in the telomeric end of c6 (peak marker D6Mit15 at 74 cM) and had a maximum LOD score of 4.6. Trmq2, in the telomeric half of c2, peaked at D2MIT483 and had a maximum LOD score of 3.41. Both of these QTLs impacted the CD4:CD8 ratios in peripheral T cells and had no impact on variation in this ratio among thymic precursors. However, heterozygosity for the H2 complex was suggestively associated (LOD score of 2.43) with increases in CD4 T cells among T cell precursors in the thymus. All of these QTLs were affected by epistatic interactions, indicating that additional modifiers in the B6 and DBA/2 genomes modulate this phenotype.

Animals↗

Desmoid tumor of the larynx complicating pregnancy: a case report.

Desmoid tumors are locally invasive fibrous neoplasms that arise from musculoaponeurotic structures. We report the first case of a desmoid tumor of the larynx complicating pregnancy. At 21 weeks' gestation fiberoptic and indirect otolaryngologic examination of the patient's larynx revealed a submucosal tumor involving the left true vocal cord, ventricle of the larynx, and false vocal cord. Histopathologic examination revealed areas of extensive fibrosis intermixed with degenerated vocal cord skeletal muscle. Despite a subtotal excisional biopsy, growth of the desmoid tumor continued during pregnancy. Endoscopic evaluation 9 weeks post partum revealed complete regression of the tumor.

Adult↗

Successful pregnancy outcome in a woman with a gain-of-function mutation of the calcium-sensing receptor. A case report.

BACKGROUND: Gain-of-function mutations of the calcium-sensing receptor gene have recently been identified as a cause of familial hypercalciuric hypocalcemia. There have been no earlier reported cases of pregnancy among patients with this disorder. CASE: A 26-year-old woman, gravida 1, para 0, was diagnosed at age 18 as being a heterozygous carrier of a mutation in the calcium-sensing receptor gene. Stable maternal hypocalcemia was achieved during pregnancy with high-dose calcium and 1,25-dihydroxyvitamin D3 therapy. Prenatal diagnosis was accomplished via amniocentesis at 16 weeks' gestation. The patient underwent cesarean delivery at 35 5/7 weeks' gestation after developing the HELLP syndrome. CONCLUSION: Patients with mutations of the calcium-sensing receptor may have a successful pregnancy outcome. This abnormality may be transmitted to the fetus via an autosomal dominant pattern.

Adult↗

Gastrointestinal absorption of insulin-like growth factor in the mouse in the absence of salivary insulin-like growth factor binding protein.

Based on previous observations of the presence of both insulin-like growth factors I and II (IGF-I and IGF-II) in murine saliva (kerr et al., Biochem Pharmacol 49: 1521-1531, 1995), the saliva from BALB/c and Non-obese diabetic (NOD) mice was examined for the presence of insulin-like growth factor binding proteins (IGFBPs). Using a western-blot type ligand binding assay with 125I-labeled IGF-I, a series of binding proteins with molecular masses (M), between 25 and 45 kDa were detected in the sera, but not saliva, from both BALB/c and diabetic NOD mice. In the diabetic NOD mice, there were detectable changes in the concentrations of several of the IGFBPs relative to BALB/c mice. Using specific antibody to the binding proteins, one of these was identified as IGFBP-2. Gavage administration of [125I]IGFI indicated substantial uptake from the gastrointestinal tract and significant tissue distribution. There was an increase in serum concentrations of radiolabeled IGF-I in diabetic NOD mice over that in BALB/c mice but less recovered from most of the tissues. Intact 125I-labeled IGF-I was extracted and purified from various tissues, following gavage, and shown to retain biological activity. Thus, the uptake of biologically active IGFs from saliva would appear to take place independently of specific binding proteins.

Animals↗

Cell cycle control in isoproterenol-induced murine salivary acinar cell proliferation.

The eukaryotic cell cycle is a summary of a complex network of signal transduction pathways resulting in both DNA replication and cell division. Cyclin-dependent kinases (CDKs) control the cell cycle in all eukaryotes, whereas other proteins, known as cyclins, act as their regulatory subunits. Chronic injection with isoproterenol (ISO) can induce acinar cell proliferation in rodent salivary glands. Cyclins and CDK proteins from control and ISO-treated murine parotid acinar cells were detected by using Western blotting techniques. By comparing the expression of these cell cycle regulatory kinases in the parotid acinar cell transition from a quiescent state to a hypertrophic state, we found rapid increases in the protein levels of all CDKs, cyclin D and proliferating cell nuclear antigen (PCNA). The highest protein levels for CDKs and cyclins appeared at about 72 hr of ISO stimulation and were coincident with the highest rate of increase in gland wet weight. After 72 hr, the increase of both cell cycle protein and gland wet weight began to subside. By using a co-immunoprecipitation method, the following cell cycle regulators (CDK-cyclin complexes) were detected, CDK4-cyclin D, CDK2-cyclin E, CDK2-cyclin A, and cdc2-cyclin B, along with an increase in kinase activity over control untreated animals. Additionally, we detected significant decreases in the newly isolated CDK inhibitor (CKI) p27kip but not Wee 1 kinase. The increased levels of CKI correlated with a decrease in kinase activity of CDK/cyclin complexes by 144 hr of chronic isoproterenol treatment. Our data suggest that the holoenzymes for cell cycle control (cyclin-CDK complexes) function as a final regulatory mechanism leading to salivary gland acinar cell proliferation. The gradual decline in protein levels of the CDKs and cyclins after 3 days of chronic treatment further indicates that ISO-induced proliferation of parotid acinar cells is self-limiting and non-tumorigenic.

Animals↗