The ureidoacetamides, a novel family of non-peptide CCK-B/gastrin antagonists.
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Acetamides↗
Biomedical subjects
G Martin
Publications and source records attributed to G Martin.
The human U1A snRNP protein regulates polyadenylation via a direct interaction with poly(A) polymerase.
The human U1 snRNP-specific U1A protein autoregulates its production by binding its own pre-mRNA and inhibiting polyadenylation. The mechanism of this regulation has been elucidated by in vitro studies. U1A protein is shown not to prevent either binding of cleavage and polyadenylation specificity factor (CPSF) to its recognition sequence (AUUAAA) or to prevent cleavage of U1A pre-mRNA. Instead, U1A protein bound to U1A pre-mRNA inhibits both specific and nonspecific polyadenylation by mammalian, but not by yeast, poly(A) polymerase (PAP). Domains are identified in both proteins whose removal uncouples the polyadenylation activity of mammalian PAP from its inhibition via RNA-bound U1A protein. Finally, U1A protein is shown to specifically interact with mammalian PAP in vitro. The possibility that this interaction may reflect a broader role of the U1A protein in polyadenylation is discussed.
Animals↗
Dopamine-induced antihypertensive effects and plasma insulin rise are blocked by metoclopramide in labetalol-treated patients.
Eleven patients with moderate to severe hypertension were studied at the Vargas Hospital of Caracas. The patients were pretreated with labetalol, 800 to 1200 mg/day, orally, over a period of 1 week, after which an intravenous infusion of dopamine, .5 to 3 micrograms/kg/minute, was given. Two intravenous dopamine infusions (30 minutes each) were performed before and after the injection of metoclopramide (30 mg, intravenous bolus). Two washout periods were also included before and after metoclopramide administration. Dopamine induced a decrease of blood pressure from 171.9 + 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mm Hg (P < .001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- .70 microU/mL to 12.09 +/- 1.83 microU/mL (P < .01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. Hypotensive responses and plasma insulin increases due to dopamine were blocked by metoclopramide, however. The authors conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in humans.
Blood Glucose↗
Function of FGF-4 in limb development.
The apical ectodermal ridge plays a central role in limb development through its interactions with the underlying mesenchyme. Removal of the AER results in cessation of limb outgrowth and leads to truncation of the limb along the proximo-distal axis. The many functions attributed to the ridge include maintenance of the progress zone mesenchyme. Here, cells are stimulated to proliferate, are maintained in an undifferentiated state, and are assigned progressively more distal positional values as the limb grows. The AER also functions to maintain the activity of the polarizing region, a region of mesenchyme which is thought to provide the primary signal for patterning along the antero-posterior axis. We have begun to explore the function of fibroblast growth factor-4 (FGF-4) during limb development. FGF-4, which encodes an efficiently secreted protein, is expressed in the AER. We have previously demonstrated that FGF-4 protein can stimulate limb mesenchyme proliferation and can induce the expression of a downstream homeobox gene, Evx-1 (homologue of the Drosophila even-skipped gene), that is normally regulated by a signal from the AER. To determine to what extent FGF-4 protein can substitute for the AER to allow normal limb outgrowth, we performed experiments on the developing chick limb in ovo. Remarkably, we find that after AER removal, the FGF-4 protein can provide all the signals required for virtually normal outgrowth and patterning of the limb.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Histamine as an autocrine growth factor in experimental mammary carcinomas.
In order to determine the role of endogenous histamine in the regulation of cell growth, the in vitro action of fluoromethyl-histidine (MFMH) was studied in experimental mammary carcinomas induced in rats. Tumor cells were cultured in soft agar using the clonogenic agar technique. The MFMH was added in different concentrations (0.01-100 microM). The effect observed was a 60% inhibition on colony formation with a maximal effect at concentrations over 10 microM. This action was completely reverted by the H2 agonists dimaprit and arpromidine with an IC50 value of 1 microM. The action of the H2 agonists when added alone was a significant increase in cell proliferation (135%), while the H1 agonist produced a dose-dependent inhibition on cell growth. In these experimental carcinomas endogenous histamine is critical for cell proliferation and one of its major effects may be the stimulation of cell growth by acting on specific H2 membrane receptors.
Animals↗
Effect of histamine on growth and differentiation of the rat mammary gland.
The presence of H1 and H2 histamine receptors and their associated second messenger systems were studied during the development of the rat mammary gland. In the tissue of the young female, histamine presented a double receptor site as previously described for experimental mammary tumors, namely a high affinity H2 site (Kd = 10 +/- 2 nM, Bmax = 1068 +/- 71 fm/mg prot.), which mediated its effect via the products of phosphoinositide hydrolysis and a low affinity H1 receptor (Kd1 = 5 +/- 2 nM, Bmax = 188 +/- 33 fm/mg prot. and Kd2 = 41 +/- 20 nM, Bmax = 1980 +/- 790 fm/mg prot. when characterized with 3H-mepyramine), coupled to adenylyl cyclase activation. On the other hand, the mammary gland of the adult rat presented these receptors coupled to the classical second messenger systems described for mammalian cells, that is, the H2 receptor produced an increase in intracellular cAMP levels and the H1 receptor increased the phosphoinositide turnover. We conclude that histamine plays a critical role during development and differentiation of the normal rat mammary gland.
Animals↗
Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: evidence of persistent surfactant deficiency.
Infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) can have initial lung atelectasis which, in survivors, gradually improves over time. To test the hypothesis that these patients could benefit from surfactant therapy, infants with CDH (born at > 34 weeks' gestation) on ECMO received either four doses of modified bovine lung surfactant extract (beractant) (surfactant group, n = 9) or an equal volume of air (control group, n = 8). Tracheal aspirate surfactant protein-A (SP-A) concentrations were initially low, and then increased over time in both CDH groups (P = .0021); however, levels remained low when compared with those of infants on ECMO who had other diagnoses (P = .04). Lung compliance (CL), time to extubation, time on oxygen, and total no. of hospital days were not different between the two groups. Infants with CDH had persistently elevated right ventricular pressure (RVP) at cessation of bypass when compared with non-CDH infants on ECMO (RVP = 53.25 mm Hg +/- 19.52 in the CDH group, 32.90 +/- 10.63 in the non-CDH group; P = .0121). The findings suggest that the postnatal surfactant deficiency may be more persistent in CDH infants than in non-CDH infants on ECMO. However, CDH remains a multifactorial condition, with delayed improvement, because of persistence of pulmonary hypertension, difficulties with vascular remodeling, degree of lung hypoplasia, or compromised respiratory mechanics.
Airway Resistance↗
Hepatic Kupffer cell function: the efficiency of uptake and intracellular degradation of 14C-labelled mitochondria is reduced in aged rats.
Uptake from the circulation and subsequent intracellular degradation of foreign and potentially harmful substances are key functions of hepatic Kupffer cells. While ageing is generally associated with decreased clearance by the reticulo-endothelial system, the effect of ageing on specific Kupffer cell functions is poorly understood. This study measured the ability of Kupffer cells of isolated perfused rat livers from young and old rats to both phagocytose and subsequently degrade exogenous radiolabelled mitochondria. Using electron microscopy and stereological techniques it was determined that there was no change in the volume density of Kupffer cells between 2 and 24 months, implying that the size of the Kupffer cell population increased (along with the total liver size) with age. However, despite this increase size there was no parallel increase in the capacity of the liver to take up or degrade radiolabelled mitochondria, implying that, in aged rats, Kupffer cell uptake and intracellular degradation was less efficient.
Aging↗
Non-toxic DNA extraction in a clinical setting.
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Blotting, Southern↗
Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, both in continuous 96-hour infusion, in the treatment of locally advanced head and neck cancer.
In this study, 79 patients with locally advanced head and neck cancer were treated with induction chemotherapy. Cisplatin, 25 mg/m2, and 5-fluorouracil (5-FU), 1000 mg/m2, were employed, both of them in 24-hour continuous infusion over 96 hours, four cycles. The patients later underwent surgery and/or radiation therapy. The response to chemotherapy was 49%: of the complete responses (CR), 56% were histological; 29% were partial responses (PR). With the administration of the fourth cycle, CR increased from 30% to 49%. Once the complete treatment had been finished, 75% of CR and 5% PR were achieved. With a maximum follow-up period of 44 months, overall survival stands at 50%.
Antineoplastic Combined Chemotherapy Protocols↗
Inappropriate use of oxygen: loss of a valuable healthcare resource.
Oxygen (O2) use is well established in hospitalized patients with hypoxemia. However, its value in patients without hypoxemia is not well documented. The authors conducted a retrospective study to evaluate the excess use of O2 and the resulting loss of resources. They established criteria for O2 use by faculty consensus. Ninety-six patients (102 admissions) receiving O2 between August and October 1991 were identified. Principal discharge diagnoses included cardiac diseases (37%), pulmonary diseases (26.5%), and miscellaneous (36.5%). Cumulative oxygen use was 9,742 hours. Appropriate O2 amounted to 3,272 hours (34%), and inappropriate O2 use was 6,470 hours (66%). The billing for O2 use was $38,468, of which $25,880 constituted inappropriate use. In 1991, there were 7,743 admissions, with oxygen charges of $1.06 million. Extrapolation of the data shows billing for inappropriate oxygen was $697,000. The authors conclude that inappropriate use of oxygen results in significant loss of resources. Educational efforts to decrease this loss and evaluate its impact on patient outcome is needed.
Adolescent↗
Characteristics of successful health care organizations. The HR dimension.
Considerable attention is being given in the UK to the issue of identifying "what is it" that makes for success in health care organizations. The HAY Group has developed a worldwide database on the key human resource issues that are linked to success. Outlines some of the research. Drawing mainly on data from the USA, Canada, UK, Australia and The Netherlands, the research finds clear evidence of successful agencies adopting a strategic approach to the issues and then undertaking specific activities in organization design, management culture, rewards and management characteristics. Identifies a series of good practices and trends, and organizations can assess their own current position on a number of dimensions.
Data Collection↗
Parental bonding and vulnerability to adolescent suicide.
Part of a series of studies into early detection in adolescent suicide, this study investigated relationships between parenting style and suicidal thoughts, acts and depression. Students (mean age 15 years) from 4 randomly chosen high schools completed self-report questionnaires containing the Parental Bonding Instrument (PBI) and the Youth Self Report, which provided information about suicide ideation, deliberate self-harm and depression. Significant differences for mean scores on the PBI subscales were noted between cases and noncases of depression, suicidal thoughts and deliberate self-harm. Assignment by adolescents of their parents to the "affectionless control" quadrant of the PBI doubles the relative risk for suicidal thoughts, increases the relative risk for deliberate self-harm 3-fold and increases the relative risk for depression 5-fold. It seems that the PBI may play a role in identification of vulnerable adolescents; further, it both elucidates aspects of adolescent-parent interaction and points toward areas for intervention with at-risk adolescents. We recommend the use of the PBI in early detection studies of adolescent suicide.
Adolescent↗
Predicting suicide attempts among adolescents.
This study set out to investigate the utility of 4 often referred to behavioural antecedents of suicide attempts--suicide ideation, plans, threats and deliberate self-harm--in the prediction of suicide attempts and the identification of suicide attempters and nonattempters among adolescents. A total of 156 male and 151 female students aged between 14 and 17 years (mean = 15.8) attending one randomly chosen metropolitan state high school completed a questionnaire concerning a number of aspects of suicidal behaviour. The findings indicated that suicide ideation, plans and threats, and deliberate self-harm are associated with suicide attempting and that a combination of suicide plans and deliberate self-harm present a particularly worrying mixture. Further, a composite index of suicidality was demonstrated to have some utility in the identification of suicide attempters and nonattempters. These findings add further weight of evidence to the suggestion that adolescents who enter the spectrum of suicide behaviours are at high risk of making a suicide attempt, although this requires further investigation in a prospective study.
Adolescent↗
Morphological characterization of three phenotypes of the isopod Armadillidium vulgare.
The morphological characteristics and ommochrome quantity in the integument of red, white, and wild type (black-grey) Armadillidium vulgare were studied. The red phenotype was found to possess two kinds of immature ommochrome pigment granules within its pigment cells, in addition to mature pigment granules. The immature granules seemed to contain uniformly distributed fibrilles, or to have an electron-dense central region surrounded by an electron-lucent outer edge. Since these immature pigment granules were typically observed to be distributed along with the mature ones, and were also more easily extractable than the wild type's, it is hypothesized that ommochrome granule maturation in the red phenotype may occur slowly due to a defect in the pigment granule internal process which combines pigments with matrix proteins. Regarding the white phenotype, although its pigment cells were undeveloped, several large-sized vesicles containing a small amount of electron-dense material appeared in the pigment cell cytoplasm. The wild and red type males of A. vulgare were found to have an ommochrome content twice as large as that of the corresponding females, with no ommochrome pigment being detected in the white phenotype. The genetic relationship between the white and red phenotypes was discussed using as a basis the observed pigment granule structure.
Animals↗
Invasion of rabbit ileal tissue by Enterobacter cloacae varies with the concentration of OmpX in the outer membrane.
The outer membrane protein OmpX of Enterobacter cloacae shows high amino acid homology with virulence proteins PagC and Rck from Salmonella typhimurium and with Ail from Yersinia enterocolitica. Here we demonstrate a role for OmpX in the invasion of rabbit ileal tissue by E. cloacae. An organ culture system was used for maintenance of rabbit gut tissue during the experiments. The invasiveness of three E. cloacae strains, which differed in OmpX content, were compared with each other and with that of Salmonella typhimurium TML (a highly invasive strain) and S. typhimurium LT7 (a noninvasive strain). There was no significant difference between the invasiveness of the wild type and that of an ompX deletion mutant strain of E. cloacae; they were equally as invasive or less invasive than S. typhimurium LT7. The invasiveness of an OmpX overproducer strain of E. cloacae was 10-fold higher than that of its immediate parent carrying only the multicopy plasmid, higher than that of S. typhimurium LT7, but lower than that of S. typhimurium TML. The invasiveness of E. cloacae thus varied directly with the level of OmpX in the outer membrane in rabbit ileal enterocytes challenged in situ.
Animals↗
[Factors of recurrence in Crohn disease].
The surgical treatment of complications of Crohn's disease is often postponed, because of the threat of short gut and high recurrence rates. We reviewed retrospectively 286 cases of intestinal resection to evaluate factors influencing the recurrence of Crohn's disease after surgery. Recurrence was defined as the need for reoperation. Risk factors used as independent variables are all subject of controversy in recent literature. These factors included: smoking, blood transfusion, contamination, localisation of the disease, length of resection, microscopic margins and the duration of follow-up. A logistic regression model was calculated, using recurrence as the dependent variable. The mean follow-up is 55 months. Kaplan Meier was used to measure the recurrence rate. Duration of follow-up is the most important variable. The length of resection and the positive margins can statistically predict recurrence (p = 0.046 et p = 0.016), both having a predictive value of 72%. A resection with clear margins decreases the recurrence rate significantly (15%) (p = 0.0025).
Adolescent↗
[The effect of coccidiostats on the growth capacity and the survival ability of Salmonella live vaccine agents].
Anticoccidial agents are obligatory feed additives during several rearing periods of poultry. The success of an oral immunization of young chicken with Salmonella live vaccines depends on the insensitivity of the vaccine strain against such anticoccidial agents because the vaccination success depends on the survival of the vaccine strain in the gut of the chick and the temporary colonization of lymphatic tissue. We investigated the in vitro sensitivity of the vaccine strain in the S. typhimurium live vaccine "Zoosaloral H" registered for the vaccination of poultry in Germany in connection with often used anticoccidial agents (Diclazuril, Monensin, Narasin and Salinomycin). No differences in growth and survival between the samples containing and lacking anticoccidial agents were found even by using double amounts of the permitted concentration of the anticoccidial agents. No negative effects of the tested anticoccidial agents on Salmonella being used as oral live vaccines in poultry should be expected.
Animals↗