Proceedings of the Society for Experimental Biology and Medicine最新文献

Phytoestrogens are a normal constituent of soy protein and have been shown to have anti-inflammatory activity in various in vitro and in vivo models. The present study was designed to determine if a diet enriched in the phytoestrogen isoflavones, genistin and daidzin, would alter the antigen-induced cellular infiltration, particularly eosinophilia, characteristic of a guinea pig model of asthma. Throughout the duration of the study, guinea pigs were maintained on a control diet (standard guinea pig chow) or the same diet enriched in isoflavones. The animals were placed on the diet 2 weeks prior to active sensitization with ovalbumin (OA). Three weeks after sensitization, animals were challenged with OA aerosol. The cellular infiltration into the lung and protein and red blood cells (RBC) in the bronchoalveolar lavage fluid (BAL) were determined 17 hr later. In animals maintained on the control diet, OA aerosol challenge resulted in the expected increase in eosinophils in both the BAL and the lung tissue, an increase in neutrophils in the BAL, and an increase in protein and the number of RBC in the BAL. In contrast, in animals maintained on the isoflavone diet, the OA-induced eosinophilia in the lung tissue was significantly attenuated. In addition, OA challenge caused a greater increase in BAL protein in animals maintained on the isoflavone diet compared with animals on the control diet. Our results indicated that a diet enriched in isoflavones results in reduced antigen-induced eosinophilia in the lung in the guinea pig model of asthma. However, this beneficial anti-inflammatory effect of dietary phytoestrogens is accompanied by a potentially detrimental increase in antigen-induced leakage of protein into the airspace.

Fertilization, implantation, and placentation are dynamic cellular events that require not only synchrony between the maternal environment and the embryo, but also complex cell-to-cell communication. This communication involves integrins, a large family of proteins involved in the attachment, migration, invasion, and control of cellular function. Over the past decade, investigators have learned that integrins participate in multiple reproductive events including fertilization, implantation, and placentation in many species. This review will describe: (i) the expression of integrins on gametes and during the establishment and development of the placenta; (ii) regulatory pathways for controlling expression of integrins in the uterus and developing placenta; (iii) the function of integrins as determined by null-mutations; and (iv) reproductive dysfunction in women related to inappropriate integrin expression in the uterus and/or placenta.

This study is a continuation of previous work searching for possible anatomic reasons to explain variable and usually unpredictable postoperative pain and dysfunction after the same nerve losses with similar neck dissection operations. The study consisted of dissections of 19 deceased unpreserved elderly subjects arterially injected with dyed latex. Of the 19 subjects, 14 had brain stem and cervical spinal cord dissections, and all had neck dissections. The findings suggested two possible anatomic reasons for the pain and dysfunction: (i) The intracranial anatomy of the lower four cranial nerves, the glossopharyngeal (IX), the vagus (X), the spinal accessory (XI), and the hypoglossal (XII), was just as variable as the previously reported peripheral spinal accessory nerve plexus; and (ii) Both the intracranial and neck dissections indicated that the blood supply to the lower four cranial and cervical nerves, particularly to the brachial plexus, could be impaired by atherosclerosis and/or neuroforaminal impingement or operative loss. This loss of blood supply theoretically could result in ischemia as another possible cause of postoperative pain and dysfunction. It is concluded that because of the potential importance of each nerve and vessel, often unknown at operation, it is very important to spare as many of them as possible to avoid subsequent painful impairment.

Arginine-specific mono-ADP-ribosylation of proteins and arginine-specific mono-ADP-ribosyltransferase occur in heart. We developed a polyclonal antiserum, R-28, against ADP-ribosylpolyarginine that recognized mono-ADP-ribosylated proteins and identified the major mono-ADP-ribosylation products of quail heart. Treatment of Immobilon-bound ADP-ribosylated Gs protein with hydroxylamine under conditions that remove ADP-ribose from its arginines eliminated R-28 immunoreactivity to Gs. Also, R-28 immunoreactivity to quail heart proteins was removed by NaOH and phosphodiesterase I treatments. Similar treatment with mercuric chloride did not remove the immunoreactivity but did remove exogenously (via in vitro pertussis toxin treatment) added ADP-ribose from cysteine of cardiac Gi/Go proteins. The antiserum did not appear to react with ADP-ribosylasparagine of Rho (formed by C3 toxin), ADP-ribosyldiphthamide of elongation factor 2 (formed by diphtheria toxin) in quail heart preparations, or polyADP-ribosylated proteins of a neonate rat cardiac nuclear preparation. Thus, the R-28 antiserum appears to contain predominantly antibodies directed against ADP-ribosylarginine. To test the usefulness of R-28, immunoblotting of subcellular fractions of quail heart was performed. R-28 showed the greatest immunoreactivity in the sarcolemma with significant immunoreactivity in denser membrane fractions. The cytosol also contained an immunoreactive band distinct from those found in the membranes. Hydroxylamine treatment eliminated immunoreactivity in the sarcolemma and denser membrane fractions but not the cytosol, suggesting the membranous immunoreactive bands contain ADP-ribosylarginine. In conclusion, a polyclonal antiserum that recognizes ADP-ribosylarginine proteins has been raised. The usefulness of the antiserum is demonstrated by the characterization of endogenous arginine mono-ADP-ribosylation products in quail heart. The quail heart has several sarcolemmal and denser membrane fraction proteins that appear to be mono-ADP-ribosylated on arginines.

Previously, we showed that the increase in pancreatic enzyme secretion was lower after feeding a casein diet containing fat than that after feeding a fat-free casein diet in chronically bile-pancreatic juice (BPJ)-diverted rats. In the present study, we determined whether the suppressive effects of fats on flow volume of BPJ and pancreatic enzyme secretion depend on delaying gastric emptying and examined the characteristics of the suppression with intraduodenal instillation of soybean oil or lecithin in BPJ-diverted rats. The study was conducted as three separate experiments using conscious rats with chronic BPJ diversion by means of a common bile-pancreatic duct catheter. The flow volume of BPJ and the secretion of pancreatic amylase and trypsin were determined after intraduodenal instillation of the test solution. Exocrine pancreatic secretion was strongly stimulated by administration of guanidinated casein hydrolysate (HGC, 150 mg/ml) in chronic BPJ-diverted rats. However, pancreatic secretion after administration of an emulsion containing HGC with either soybean oil (100 mg/ml) or mixed fat (50 mg/ml soybean oil + 50 mg/ml lecithin) was much lower than that after administration of HGC alone. In contrast, administration of the soybean oil emulsion without HGC resulted in a small, but significant increase in the volume of BPJ. The suppressive effects of soybean oil (100 mg/ml) on the increases in the BPJ flow and enzyme secretion were similar to those of sodium taurocholate (10 mg/ml), and there was no additive effect of soybean oil on taurocholate suppression. In conclusion, duodenally instilled soybean oil suppressed increases in flow volume of BPJ and pancreatic enzyme secretion induced by HGC in chronic BPJ-diverted rats, showing that the suppressive effect of the fat does not depend on delaying gastric emptying.

The environment in which the encounter of antigen with the immune system occurs determines whether tolerance, infectious immunity, or autoimmunity results. Geographical areas with low supplies of vitamin D (for example Scandinavia) correlate with regions with high incidences of multiple sclerosis, arthritis, and diabetes. The active form of vitamin D has been shown to suppress the development of autoimmunity in experimental animal models. Furthermore, vitamin D deficiency increases the severity of at least experimental autoimmune encephalomyelitis (mouse multiple sclerosis). Targets for vitamin D in the immune system have been identified, and the mechanisms of vitamin D-mediated immunoregulation are beginning to be understood. This review discusses the possibility that vitamin D status is an environmental factor, which by shaping the immune system affects the prevalence rate for autoimmune diseases such as multiple sclerosis, arthritis, and juvenile diabetes.

The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A-IV gene in the intestinal epithelial cell line Caco-2 was examined by semiquantitative RT-PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A-IV mRNA levels were increased in response to peptide YY in a dose- and time-dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A-IV. In contrast, apolipoprotein A-I, B, and C-III mRNA did not respond to peptide YY. Differentiated Caco-2 cells expressed Y1- but not Y2- and Y5-receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A-IV gene expression, likely via the Y1-receptor subtype in intestinal epithelial cells.

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK-8. Results showed that basal and CCK-stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high-fat diet when compared with rats given a high-carbohydrate diet. Forty-eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high-fat diet showed significantly lower basal and CCK-stimulated amylase release when compared with those on a high-carbohydrate diet. Histology of the pancreas of rats on a high-carbohydrate diet appeared normal; however, the pancreas of rats on high-fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high-fat diet, that were not found in rats on a high-carbohydrate diet; further, they support the contention that a high-fat diet has a deleterious effect on the pancreas.

We hypothesized that myocardial stunning would be reversed through increased cyclic GMP caused by nitroprusside, and that this would be accomplished through a decreased proportion of regional work during diastole. Hearts were instrumented to measure left ventricular pressure, and regional myocardial mechanics were recorded using a miniature force transducer and ultrasonic dimension crystals in eight open-chest anesthetized dogs. Following baseline (CON), the left anterior descending coronary artery (LAD) was occluded for 15 min, followed by a 30-min recovery (STUN). Then intracoronary LAD infusion of sodium nitroprusside (NP) (4 microg/kg/ min) was begun. The time delay (msec) to regional shortening increased significantly from 18+/-13 to 73+/-13 following stunning, but was reduced to 49+/-18 by NP. Total regional work (g*mm/min) at baseline (1368+/-401 CON) was unchanged with stunning (1320+/-333 STUN), but reduced (961+/-240) following NP. Time to peak force development (msec) increased significantly with stunning from 284+/-13 (CON) to 333+/-11 (STUN), but was reduced to 269+/-12 following NP. The percentage work during systole was reduced from 96%+/-2% (CON) to 77%+/-7% (STUN), but returned to 98%+/-1% with NP. Regional O2 consumption was unaffected by either treatment. Cyclic GMP was unchanged by stunning (2.9+/-0.3-2.9+/-0.4 pmol/g) but increased significantly with NP (4.6+/-0.6). These data indicated that regional myocardial stunning could be attenuated by nitroprusside, which increased cyclic GMP, decreased contractile delay, increased the proportion of work done during systole, and reduced time of shortening.