Blocking of protein pancreatic secretion by maximal secretion infusion in the dog

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 c.u./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus. The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections thoughout the three hours. The same protocol was followed in anesthetized dogs subjected to a mind line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlated well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose. The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.     

Effects of glucagon on pancreatic secretion in the dog

About 85-90% of cytoplasmic protein synthesized by young reticulocytes is globin, and about 10% is a polypeptide (I) of molecular weight 64,000 daltons. Maturation of reticulocytes is accompanied by selective reduction in the synthesis of polypeptide I, relative to globin; mature reticulocytes synthesize globin at a high level but make no detectable polypeptide I. Studies in which RNA from young and old reticulocytes was translated in a wheat germ cell-free extract showed that reduction in synthesis of polypeptide I was correlated with a reduction in the amount of translatable mRNA for this protein. Differential destruction of mRNA thus is an important factor in determining the types of proteins made during the final stages of erythropoiesis.     

Effect of histamine on intestinal fluid secretion in the dog

Intra-arterial infusion of histamine into the small intestine caused about a onefold increase of blood flow, edema of the intestinal tissues and mesentery, and produced a copious secretion of fluid. The jejunal secretions had an ionic composition similar to that of plasma, whereas ileal secretions contained high concentrations of HCO3 with relative low concentrations of Cl. The secretions contained protein (1.5 +/- .2 g/100 ml, range 0.5-2.4) with a similar electrophoretic pattern of plasma protein. When lissamine green was present in the blood, it also appeared in the secretion to a considerable concentration. It is inferred from these findings that a major mechanism of fluid secretion by the action of histamine involves a filtration process across the mucosal epithelium by the incrreased tissue fluid pressure due to extensive capillary leak.     

Immunolike growth hormone substance in tissues from human embryos/fetuses and adults

GH immunolike reactivity was measured by RIA and IRMA tests in the extracts of tissues from human fetuses (8-32 weeks) and adults. For some fetal tissues a comparison was made with the T4 values obtained in a previous study. Both hormones were already measurable in peripheral tissues at 8 weeks of gestation. The increase in GH was faster than for T4 and it reached the zenith at approximately 20 weeks; thereafter, the GH concentration declined until delivery. In contrast, T4 progressively increased until term. Thirteen tissues were studied both in fetuses and in adults: the GH concentration was about 10 times higher in fetal tissues, with the exception of the brain and the pancreas. The brain showed the lowest GH concentration throughout fetal life and adulthood, whereas the highest GH levels were recorded in adults' pancreas, but they resulted to be artifacts since the RIA values were not confirmed by the IRMA test. In both groups of subjects the highest GH concentrations were found in kidneys, liver and small intestine; the lowest, beyond the brain, in red muscle and cartilage. Thus, the pattern of the quantitative distribution of GH in fetal tissues is the same as in adults, suggesting a functional role of the hormone in the developing human during the prenatal period, in contrast with the concept that high tissue levels of GH are a mere reflection of high GH blood levels. Moreover, in all tissues examined no correlation was found between GH and T4 concentration.     

Intracerebroventricular neuropeptide Y increases gastric and pancreatic secretion in the dog

BACKGROUND: Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion. METHODS: Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied. RESULTS: ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula. CONCLUSIONS: ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.     

Relationship between age of blastocyst formation and interferon-tau secretion by in vitro-derived bovine embryos

The quantitative analysis of a three-dimensional (3-D) intracoronary ultrasound (ICUS) image data set permits a more comprehensive assessment of coronary arterial segments. The 3-D image sets are generally acquired during continuous motorized pullbacks. However, the cyclic changes of vascular dimensions and the cyclic spatial displacement of the ICUS transducer relative to the vessel wall can result in characteristic image artifacts, which may limit the applicability of quantitative automated analysis systems. This limitation may be overcome by an ECG-gated image acquisition. In the present study we acquired in vivo (1) nongated and (2) ECG-gated 3-D ICUS image sets of 15 human atherosclerotic coronary arteries and performed a computer-assisted contour detection of the lumen and total vessel boundaries. Total vessel and lumen volumes measured significantly larger in the nongated versus ECG-gated end-diastolic image sets (753+/-307 mm3 vs. 705+/-305 mm3; 411+/-154 mm3 vs. 388+/-165 mm3, both: P < 0.05). Both end-diastolic and systolic measurements were available in nine arteries, showing a larger total vessel and lumen volume at systole (664+/-221 mm3 vs. 686+/-227 mm3, P=0.03; 384+/-164 mm3 vs. 393+/-170 mm3, P=0.08). The differences observed may be of particular interest for volumetric ICUS studies, addressing presumably small differences in vessel or lumen dimensions.     

12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation

12-Hydroxyeicosatetraenoic acid (12-HETE) is one of the major metabolites formed from arachidonic acid in platelets. We have recently shown that the in vitro metabolism of 12-HETE by human leukocytes, with and without stimulation, is effectively inhibited by the addition of physiological concentrations of albumin, probably by sequestration of the compound. In the present paper, we have studied the in vivo metabolism of 12-HETE in the rabbit, using either [1-14C]- or [14C(U)]12-HETE. Distribution of radioactivity was followed in urine, plasma, and bile, as well as in a number of tissues. In most of the tissues examined, the hydrophilic radioactivity constituted more than 50% of the total radioactivity after 20 min. When the lipophilic fraction was analyzed, around 15% of the radioactivity was shown to be unesterified 12-HETE, and only a very minor part could be detected as metabolites. The dominating lipophilic compound in the circulation after i.v. administration of radiolabeled 12-HETE was at all time points (1-60 min.) the parent compound, as analyzed by HPTLC and HPLC. A comparison of the plasma metabolite profiles obtained when [1-14C]- and [14C(U)]12-HETE were used displayed almost identical patterns, thus indicating that beta-oxidized metabolites either were not formed or were rapidly removed from the circulation. The appearance of large amounts of water-soluble radioactivity with time supported the latter conclusion. Several minor metabolites were seen that chromatographed in the dihydroxy acid region as judged by HPLC and TLC. The major one of these compounds represented about 10% of the lipophilic plasma radioactivity after 60 min., while unmetabolized 12-HETE at this stage still represented about 30%. The metabolite had a polarity similar to 12,20-dihydroxyeicosatetraenoic acid; however, when chromatographed together, these two compounds separated, indicating a different structure of the metabolite. Our findings are in agreement with in vitro data concerning the protective effect of albumin on the metabolism of 12-HETE and is the first extensive metabolic study of 12-HETE in vivo covering all metabolic possibilities involving the carbon skeleton.     

The betaL integrin subunit is necessary for gastrulation in sea urchin embryos

Integrins are a family of cell adhesion molecules reported to mediate cellular interactions essential for normal embryonic morphogenesis. Here we describe a beta integrin subunit that is expressed during early embryogenesis in the sea urchin embryo and appears to be necessary for normal development. The deduced amino acid sequence of betaL is similar to vertebrate beta integrin subunits, but is most closely related to the sea urchin betaG subunit. Northern blots show that betaL is expressed at all stages with maximum expression beginning during gastrulation. Immunolocalization and in situ RNA hybridization show that in blastulae betaL is expressed in the blastoderm and by the ring of bottle cells in the vegetal plate during the initial phase of gastrulation. Presumptive secondary mesenchyme cells express high levels of betaL throughout elongation of the archenteron and in the pluteus betaL is expressed by blastocoelar cells, skeletal mesenchyme, and pigment cells. Antibodies and Fab fragments against betaL block spreading of dissociated embryonic cells on RGD (arginine-glycine-aspartate)-containing substrates. Treating embryos with anti-betaL antibodies blocks the initial phase of gastrulation and interferes with the organization of actin filaments. Prior to gastrulation, the antibodies cause thickening of the blastoderm and later in development defects in skeletal patterning result. Probing for antibody in treated embryos indicates that it penetrates the ectoderm to cells within the blastocoel and is actively endocytosed. We propose that betaL forms receptors that bind to RGD-containing ligands and anchors actin filaments. These receptors appear to be essential in several aspects of morphogenesis.     

Temperament and substance abuse in schizophrenia: is there a relationship?

Dyspnea may be easily appreciated during exercise with dyspneic scales, but methodological standardisation still needs to be specified. Authors review the basic physiological mechanism relating dyspnea to indices obtained during a stress test. They propose to use the dyspnea/VE relationship. With the concept of dyspneic threshold (close to the ventilatory threshold) and the ramp that both could be modified (for instance by rehabilitation programmes including exercise training). Interpretation of dyspnea during an exercise test obviously needs to be integrated with other parameters studied during exercise.     

Adrenomedullary secretion of epinephrine is increased in mild essential hypertension

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure.     

Ventilation is stimulated by small reductions in arterial pressure in the awake dog

Changes in arterial pressure commonly accompany respiratory adaptations. The purpose of this study was to determine, in awake dogs (n = 6), the degree to which small acute decreases in arterial pressure affect ventilation and acid-base balance. Mean arterial pressure (MAP) was reduced by 6 +/- 2, 10 +/- 3, and 16 +/- 2% by intravenous infusion of sodium nitroprusside for sequential 20-min periods. In another experiment, the ventilatory response to hypercapnia was determined during MAP reduction of 16 +/- 3%. Step reductions in MAP were accompanied by increases in minute ventilation (maximum increase 152 +/- 75%) and step reductions in arterial PCO2 (PaCO2; maximum reduction -4.8 +/- 0.8 Torr). Although eupneic PaCO2 threshold was lowered during MAP reduction, ventilatory sensitivity to CO2 remained unchanged. Despite the lowered PaCO2, arterial [H+] remained constant (acid-base balance was maintained) as a result of a concurrent decrease in strong ion difference. Plasma renin activity increased during MAP reduction (93 +/- 39%) and may have contributed to the increase in minute ventilation, inasmuch as angiotensin II can stimulate respiration by a central mechanism. Evidence is provided that nitroprusside is unlikely to be a primary factor in these hypotensive responses. We conclude that relatively modest decreases in MAP have a consistent stimulatory effect on respiratory control. Therefore it is important to take into account effects of small changes in MAP when interpreting mechanisms for respiratory responses in awake animals.     

Downregulation of atrial markers during cardiac chamber morphogenesis is irreversible in murine embryos

Vertebrate cardiogenesis is a complex process involving multiple, distinct tissue types which interact to form a four-chambered heart. Molecules have been identified whose expression patterns co-segregate with the maturation of the atrial and ventricular muscle cell lineages. It is not currently known what role intrinsic events versus external influences play in cardiac chamber morphogenesis. We developed novel, fluorescent-based, myocardial, cellular transplantation systems in order to study these questions in murine embryos and report the irreversible nature of chamber specification with respect to the downregulation of atrial myosin light chain 2 (MLC-2a) and alpha myosin heavy chain (alpha-MHC). Grafting ventricular cells into the atrial chamber does not result in upregulation of MLC-2a expression in ventricular cells. Additionally, wild-type ventricular muscle cells grafted into the wild-type background appropriately downregulate MLC-2a and alpha-MHC. Finally, grafting of RXRalpha gene-deficient ventricular muscle cells into the ventricular chambers of wild-type embryos does not rescue the persistent expression of MLC-2a, providing further evidence that ventricular chamber maturation is an early event. These studies provide a new approach for the mechanistic dissection of critical signaling events during cardiac chamber growth, maturation and morphogenesis in the mouse, and should find utility with other approaches of cellular transplantation in murine embryos. These experiments document the irreversible nature of the downregulation of atrial markers after the onset of cardiogenesis during ventricular chamber morphogenesis and temporally define the response of cardiac muscle cells to signals regulating chamber specification.     

N-linked oligosaccharide processing is not necessary for glycoprotein secretion in plants

Mitochondria contain a potassium specific channel (mitoKATP channel) sensitive to ATP and antidiabetic sulfonylureas. The mitochondrial KATP channel plays an important role in the mitochondrial volume control and in regulation of the components of protonmotive force. This minireview describes the properties and current hypotheses concerning the function of mitoKATP channel.     

Oral-aboral ectoderm differentiation of sea urchin embryos is disrupted in response to calcium ionophore

Cognitive-behavioral therapy (CBT) has been shown to be a highly effective form of treatment for patients with bulimia nervosa and anorexia nervosa. Issues of satiety disturbances, food restriction, and food choice are central to this form of therapy; however, ingestive behavior research that directly addresses these issues in eating disorder patients has often been overlooked by clinicians. These areas of research are reviewed and the implications of the findings for more effective CBT therapy with anorexics and bulimics are discussed.     

The dynactin complex is required for cleavage plane specification in early Caenorhabditis elegans embryos

BACKGROUND: During metazoan development, cell diversity arises primarily from asymmetric cell divisions which are executed in two phases: segregation of cytoplasmic factors and positioning of the mitotic spindle - and hence the cleavage plane -relative to the axis of segregation. When polarized cells divide, spindle alignment probably occurs through the capture and subsequent shortening of astral microtubules by a site in the cortex. RESULTS: Here, we report that dynactin, the dynein-activator complex, is localized at cortical microtubule attachment sites and is necessary for mitotic spindle alignment in early Caenorhabditis elegans embryos. Using RNA interference techniques, we eliminated expression in early embryos of dnc-1 (the ortholog of the vertebrate gene for p150(Glued)) and dnc-2 (the ortholog of the vertebrate gene for p50/Dynamitin). In both cases, misalignment of mitotic spindles occurred, demonstrating that two components of the dynactin complex, DNC-1 and DNC-2, are necessary to align the spindle. CONCLUSIONS: Dynactin complexes may serve as a tether for dynein at the cortex and allow dynein to produce forces on the astral microtubules required for mitotic spindle alignment.     

The yellow variegated mutant of Arabidopsis is plastid autonomous and delayed in chloroplast biogenesis

The yellow variegated mutant of Arabidopsis thaliana is characterized by bright-yellow true leaves that turn green- and white-sectored as leaf development proceeds. Variegation is due to the action of a nuclear recessive gene. Whereas cells in the green sectors contain morphologically normal chloroplasts, cells in the yellow and white sectors are heteroplastidic and contain plastids with rudimentary lamellar structures, as well as some normal-appearing chloroplasts. This indicates that plastids in yellow variegated are affected differently by the nuclear mutation (the mutant is "plastid autonomous"). Genetic analyses have revealed that yellow variegated is an allele of the var2 locus, and that defective plastids are not maternally inherited. The traits of plastid autonomy and lack of maternal inheritance of the plastid defect set var2 apart from other nuclear gene-induced variegations and define a novel class of variegation mutant. The primary lesion in var2 probably does not involve a blockage in the pathways of pigment biosynthesis. Under high temperatures or low light conditions, plant growth is retarded and mutant plants are nearly all-green. Considered together, our data suggest that var2 is delayed in chloroplast biogenesis. We suggest that the stochastic pattern of variegation in the mutant may be due to an interplay of factors that regulate var2 gene expression and factors that mediate rates of cell and plastid division. Plastids with a critical threshold of the partially functional var2 protein are green, while plastids containing less than the threshold of var2 activity are white.