A variety of solid tumors secrete proteins that are immunochemically distinct from parathyroid hormone (PTH) but activate PTH-responsive adenylate cyclase. Such PTH-like have been proposed as mediators the hypercalcemia and hypophosphatemia frequently associated with malignancies. We purified to apparent homogeneity a protein molecular weight 6,000, is produced by human renal carcinoma cells. The amino-terminal sequence PTH were found display at least five identities in first 13 positions....

ALTHOUGH osteoporosis has long been considered a disease of women, in the earliest reports epidemiology it was apparent that classical age-related increase fractures seen women is evident men as well. Only last few years recognized problem represents an important public health issue and presents unique array scientific challenges opportunities (1–3). Here we examine compare its pathophysiology clinical presentation with parallel processes women. Women exhibit dramatic bone mass begins during...

Experimental murine genetic models of complex human disease show great potential for understanding pathogenesis. To reduce the time required analysis such from many months down to milliseconds, a computational method predicting chromosomal regions regulating phenotypic traits and database single nucleotide polymorphisms were developed. After entry information obtained inbred mouse strains, genotypic is analyzed in silico predict trait.

The development of osteoporosis involves the interaction multiple environmental and genetic factors. Through combined genomic approaches, we identified lipoxygenase gene Alox15 as a negative regulator peak bone mineral density in mice. Crossbreeding experiments with knockout mice confirmed that 12/15-lipoxygenase plays role skeletal development. Pharmacologic inhibitors this enzyme improved strength two rodent models osteoporosis. These results suggest drugs targeting pathway merit...

Chiral resolution of a number cationic drugs forensic interest (amphetamine, methamphetamine, cathinone, methcathinone, cathine, cocaine, propoxyphene, and various alpha-hydroxyphenethylamines) is achieved via capillary electrophoresis (CE) with added cyclodextrins (CDs), including novel mixtures neutral anionic CDs. In the latter studies, migration speed are readily adjusted by varying ratio two CDs, as CD acts counter-migrating complexing reagent. The CD, heptakis(2,6-di-O-methyl)-beta-CD,...

Abstract Peak bone mass is a major determinant of risk osteoporotic fracture. Family and twin studies have found strong genetic component to the determination mineral density (BMD). However, BMD complex trait whose expression confounded by environmental influences polygenic inheritance. The number, locations, effects individual genes contributing natural variation in this are all unknown. Experimental animal models provide means circumvent complicating factors, development dense maps based...

Clinical features of adrenal steroid deficiency occur in patients with the acquired immunodeficiency syndrome (AIDS). To determine frequency aberrations peripheral levels AIDS and AIDS-related complex (ARC) we measured morning recumbent plasma cortisol, deoxycorticosterone, 18-hydroxydeoxycorticosterone (18-OHDOC), corticosterone, aldosterone, 18-hydroxycorticosterone concentrations before after administration 0.25 mg ACTH (Cosyntropin) 74 randomly selected hospitalized 19 ARC. Basal (0800...

Abstract Peak bone mass is a major determinant of osteoporotic fracture risk. Gender differences in peak acquisition are well recognized humans and may account for substantial share the increased prevalence fragility fractures women compared with men. Skeletal development regulated by both heritable environmental factors. Experimental animal models provide means to circumvent complicating In this study we examined heritability mineral density (BMD) genetically distinct laboratory mouse...

Plasma triglycerides (neutral fat) may be di- vided into 1) that portion which is present during the fasting state and 2) which, after ingestion of fat, added to temporarily augments level triglycerides.The investigation deals with rela- tionship plasma free fatty acids (plasma FFA) TG) in man.From these observations a quantitative as- sessment amount FFA converted TG will presented.The data also permit calculations suggest major source TG. METHODSTwo types studies were carried out male...

Disorders of water balance are among the most common and morbid electrolyte disturbances, reflected clinically as abnormalities in serum sodium concentration. The transient receptor potential vanilloid 4 (TRPV4) channel is postulated to comprise an element central tonicity-sensing mechanism mammalian hypothalamus, activated by hypotonic stress vitro. A nonsynonymous polymorphism TRPV4 gene gives rise a Pro-to-Ser substitution at residue 19. We show that this significantly associated with...

Plasma free fatty acid (FFA) and glucose levels were measured in 44 young male subjects who received intravenous infusions of norepinephrine. Dose rates infusion independently varied. A significant dose-response relationship was noted for FFA. The time at which the peak response occurred depended on duration infusion. postinfusion fall FFA level observed, suggests that exogenous norepinephrine may inhibit endogenous lipid-mobilizing mechanisms. Submitted October 11, 1960

The melanocortin-3 receptor–deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, sensitivity salt-induced hypertension. We show here that the defective fasting-induced lipolysis, liver triglyceride accumulation, refeeding, regulation of adipostatic hypothalamic-adrenal-pituitary axes. Close examination hypothalamic-pituitary-adrenal axis showed mice...

A series of 14 patients with myocardial infarction hospitalized on a Coronary Care Unit and then transferred to general medical ward were studied by clinical observation measurement urinary catecholamine excretion. Emotional changes frequent correlated temporally at the time transfer. The incidence cardiovascular complications was reduced in prepared for transfer followed nurse physician throughout their hospitalization. findings reaffirm importance continuity care treatment infarction.

The habitual consumption of alcoholic beverages is clearly associated with low bone mass and an increased prevalence skeletal fractures. Microscopic analysis tissue from patients reveals reduced osteoblast number suppressed formation activity a relative sparing resorptive indices. decreased osteoblasts observed in subjects results either impaired proliferation or accelerated senescence. Polyamines ornithine decarboxylase (ODC), the rate‐limiting enzyme for polyamine synthesis, are essential...

Abstract Although levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention non-biologically active PTH fragments the aging kidney. In 102 normal aged 30 to 89 yr, iPTH increased 58% (r = 0.33, p < 0.001) antiserum GP-1M (which has midmolecule specificity) and 43% 0.32, CH-12M may have whole molecule specificity); urinary cAMP/GFR excretion 29% 0.22, 0.05). The results these assays were validated comparison biologically...

Osteogenesis imperfecta (OI) is a skeletal disorder primarily caused by mutations in the type I collagen genes. However, recent investigations have revealed that genes encoding for cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1) can cause severe, recessive form of OI. These reports show minimal 3-hydroxylation key proline residues as result CRTAP P3H1 deficiency and demonstrate importance to bone structure development. previously been shown stable complex with...

Urinary excretion of norepinephrine and epinephrine was measured in 30 patients with myocardial infarction for five days after admission to a cardiac care unit. Patients uncomplicated hospital courses or those primary ventricular fibrillation complete atrioventricular block showed similar pattern, ie, high initial levels slope normal range over the five-day period. multiple complications, particularly hemodynamic nature, lower different Some instances catechol elevation at time psychological...

Abstract Size and shape are critical determinants of the mechanical properties skeletal elements can be anticipated to highly heritable. Moreover, genes responsible may independent those that regulate bone mineral density (BMD). To begin identify heritable geometry, we have examined femoral cross-sectional area (FCSA) in male female mice from two inbred strains with divergent FCSA (C57BL/6 [B6] DBA/2 [D2]), a large genetically heterogeneous population (n = 964) B6D2F2 18 BXD recombinant (RI)...

Abstract Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out factors from genetic ones in humans has motivated the investigation animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD 24 recombinant inbred (RI) mouse strains, derived a cross between C57BL/6 (B6) DBA/2 (D2) progenitors (RI-BXD). distribution values among these strains indicated strong number...

Abstract The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms human ALOX12, but not ALOX15, were significantly associated with spine white men and women, suggesting that ALOX12 may contribute to normal variation BMD. Introduction: Osteoporosis is complex disease both genetic environmental risk factors. A major determinant osteoporosis BMD, which highly heritable trait. Recently, the arachidonate 15-lipoxygenase (Alox15) Materials Methods: To...