Aberrant retropharyngeal lymph nodes of a horse (Equus caballus)

The occurrence of aberrant lymph nodes, on both sides of the head of a horse, belonging to the retropharyngeal lymphocenter has been reported.     

The sea horse comes of age: Theoretical comment on Rehbein, Killiany, and Mahut (2005) and Killiany, Rehbein, and Mahut (2005).

Impairments in various aspects of learning and memory have been ascribed to the effects of damage to the hippocampal formation in adult nonhuman primates. Whether these effects reflect disturbance of a unitary process or multiple processes within the hippocampus and whether other systems may participate in these functions is unclear. After making hippocampal ablations in infant rhesus monkeys (Macaca mulatta), L. Rehbein, R. Killiany, and H. Mahut (2005) (see record 2005-06959-001) and R. Killiany, L. Rehbein, and H. Mahut (2005) (see record 2005-06959-002) reported a dissociation of effect between tasks of recognition memory and contextual retrieval (impaired) and associative learning (spared). The findings point to an ontogenetic dissociation of function within the hippocampal formation and, at the same time, support the view of the coexistence of at least two neural systems that underlie memory and learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative hypocholesterolemic effects of capybara (Hydrochoerus hydrochaeris dabbenei) oil, horse oil, and sardine oil in cholesterol-fed rats

A clinical trial was undertaken to assess the value of incorporating fluoride released from a commercially available bonding adhesive (Rely-a-Bond) to determine the extent of any protection provided against enamel decalcification. Fifty patients undergoing fixed appliance therapy were included in the trial. Contralateral quadrants were used as controls where no fluoride was present in the adhesive. Enamel decalcification after treatment and bond failure rates during treatment were investigated. A total of 366 experimental and 371 control teeth were included in the study. The results showed that 50 per cent of patients and 13.5 per cent of teeth exhibited post-treatment decalcification. The addition of fluoride to the adhesive did not significantly reduce the incidence of enamel decalcification. Bond failure rates were satisfactory for both experimental and control teeth (all under 5 per cent).     

Catheptic endopeptidases and protein digestion in the horse clam Tresus capax (Gould)

Rat fleas, Xenopsylla cheopis (Rothschild) and X. astia (Rothschild) were fed artificially on whole blood, milk and blood fractions in an attempt to identify the factor(s) which trigger ovarian maturation. Blood from the white rat, house rat, white mouse, frog, chick and man fed artificially induced vitellogenesis in over 50% of fleas of all combinations except in X. cheopis fed on chick blood. Gut distension alone had no influence on initiation of vitellogenesis as judged by feeding milk. Washed white rat blood cells resuspended in saline initiated vitellogenesis, but plasma did not. Addition to plasma of ATP, glutathione and serotonin did not initiate yolk deposition. However, raising the protein concentration of the rat plasma had a decided influence on vitellogenesis. The protein concentration of the diet appeared to be a decisive factor in initiating yolk deposition in these fleas. A change from whole blood to plasma diet caused all the mature oocytes to resorb in both the species of fleas.     

Simulation studies of African horse sickness and Culicoides imicola (Diptera:Ceratopogonidae)

A simulation model of African horse sickness in Spain was developed to investigate what factors affect the likelihood of an epidemic after the introduction of the virus. The model included 2 host species (horses and donkeys) and 1 vector species (Culicoides imicola Kieffer). Latin hypercube sampling was used for sensitivity analysis of the model, to include uncertainty in parameter estimates. In general, if an epidemic occurred most hosts were infected. The peak prevalence in midges was low, and never exceeded 3%. Midge population size, the recovery rate in horses, and the time of year when the virus was introduced were the most significant factors in determining whether or not an epidemic occurred. The uncertainty in interbloodmeal interval, removal rate (mortality and recovery) of infectious horses, midge population size, and transmission rates were significant factors in the size of the epidemic. These factors should be priorities for empirical research, and should be considered in the design of control strategies in areas at risk of virus introduction.     

Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)

Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. GIP consists of 42 amino acid residues which is derived by proteolytic processing of a GIP precursor. In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. Thus, GIP now is generally referred to as glucose-dependent insulinotropic polypeptide. It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). GIP exerts its biological actions by binding to its specific receptors, which appear to be coupled to G proteins. We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells.     

Dyspnoea due to intrathoracic haemorrhage and haemangiosarcoma in a horse (author's transl)

Post-morten examination of a fourteen-year-old mare of the Gelderland breed, which had been treated for severe dyspnoea and had subsequenlty died, revealed the presence of haemothorax, atelectasis of the lung and a metastasized haemangiosarcoma of the left ovary. The haemothorax could have resulted from rupture of one of the metastases.     

Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice

PRL is an anterior pituitary hormone that, along with GH and PLs, forms a family of hormones that probably resulted from the duplication of an ancestral gene. The PRLR is also a member of a larger family, known as the cytokine class-1 receptor superfamily, which currently has more than 20 different members. PRLRs or binding sites are widely distributed throughout the body. In fact, it is difficult to find a tissue that does not express any PRLR mRNA or protein. In agreement with this wide distribution of receptors is the fact that now more than 300 separate actions of PRL have been reported in various vertebrates, including effects on water and salt balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, and immune regulation and protection. Clearly, a large proportion of these actions are directly or indirectly associated with the process of reproduction, including many behavioral effects. PRL is also becoming well known as an important regulator of immune function. A number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL, which may act in an endocrine, autocrine, or paracrine manner, or via an increased sensitivity to the hormone. The first step in the mechanism of action of PRL is the binding to a cell surface receptor. The ligand binds in a two-step process in which site 1 on PRL binds to one receptor molecule, after which a second receptor molecule binds to site 2 on the hormone, forming a homodimer consisting of one molecule of PRL and two molecules of receptor. The PRLR contains no intrinsic tyrosine kinase cytoplasmic domain but associates with a cytoplasmic tyrosine kinase, JAK2. Dimerization of the receptor induces tyrosine phosphorylation and activation of the JAK kinase followed by phosphorylation of the receptor. Other receptor-associated kinases of the Src family have also been shown to be activated by PRL. One major pathway of signaling involves phosphorylation of cytoplasmic State proteins, which themselves dimerize and translocate to nucleus and bind to specific promoter elements on PRL-responsive genes. In addition, the Ras/Raf/MAP kinase pathway is also activated by PRL and may be involved in the proliferative effects of the hormone. Finally, a number of other potential mediators have been identified, including IRS-1, PI-3 kinase, SHP-2, PLC gamma, PKC, and intracellular Ca2+. The technique of gene targeting in mice has been used to develop the first experimental model in which the effect of the complete absence of any lactogen or PRL-mediated effects can be studied. Heterozygous (+/-) females show almost complete failure to lactate after the first, but not subsequent, pregnancies. Homozygous (-/-) females are infertile due to multiple reproductive abnormalities, including ovulation of premeiotic oocytes, reduced fertilization of oocytes, reduced preimplantation oocyte development, lack of embryo implantation, and the absence of pseudopregnancy. Twenty per cent of the homozygous males showed delayed fertility. Other phenotypes, including effects on the immune system and bone, are currently being examined. It is clear that there are multiple actions associated with PRL. It will be important to correlate known effects with local production of PRL to differentiate classic endocrine from autocrine/paracrine effects. The fact that extrapituitary PRL can, under some circumstances, compensate for pituitary PRL raises the interesting possibility that there may be effects of PRL other than those originally observed in hypophysectomized rats. The PRLR knockout mouse model should be an interesting system by which to look for effects activated only by PRL or other lactogenic hormones. On the other hand, many of the effects reported in this review may be shared with other hormones, cytokines, or growth factors and thus will be more difficult to study. (ABSTRACT TRUNCATED)     

Oestrogen receptor beta (ER beta)

Idiosyncratic adverse drug reactions are unpredictable, target multiple organ systems, and often become life-threatening events. Although the causes of idiosyncratic adverse drug reactions are not known in most cases, evidence suggests that they may be mediated through immunological mechanisms. It is generally thought that for a drug to lead to an immune response, it must first become covalently bound to a carrier protein. Since most drugs are unreactive, it is usually a reactive metabolite that is expected to form covalent adducts. However, it is not clear why more people do not develop immune reactions against drug-protein adducts. One possible explanation is that orally administered drugs may lead to oral tolerance in most individuals through mechanisms similar to that found with orally administered antigens. However, very little is known regarding the interaction of drugs with gut-associated lymphoid tissue of the small intestine, where oral tolerance can develop. As an initial step to test this hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal antiinflammatory drug, can lead to protein adducts in rat small intestine. Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of small intestine homogenates and isolated enterocyte subcellular fractions with drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid sequence analyses and by their reactions with protein-specific antibodies. The adducts were localized by immunohistochemistry and found primarily in the mid-villus and villus-tip enterocytes and also in the dome overlying Peyer's patches. Similar adducts were detected immunochemically in villus-tip enterocytes of animals treated with halothane or acetaminophen. These results show that intestinal protein adducts of drugs can be formed in gut-associated lymphoid tissue where they may lead to the down-regulation of drug-induced allergic reactions in many individuals.     

Synthesis and dopamine receptor selectivity of the benzyltetrahydroisoquinoline, (R)-(+)-nor-roefractine

Colonic variceal bleeding is a rarity and is most commonly due to portal hypertension. The present report describes a patient with portal hypertension due to portal vein thrombosis who, following esophageal transection and successful sclerotherapy, developed a massive lower gastrointestinal bleeding from colonic varices. The literature is reviewed, and the pathophysiology of this complication is discussed. Possible etiologies of this condition may be esophageal transection and devascularization, successful sclerotherapy, and extensive thrombosis of the portal vein resulting in obliteration of the coronary-azygous anastomotic system. In such a situation other potential sites of portosystemic anastomoses, such as the colon, may be opened up, resulting in the development of colonic varices. Indeed, the incidence of colonic varices in two series after sclerotherapy for esophageal varices was 60-100%. Of 33 candidates evaluated for liver transplantation, colonic varices were found in 1.     

Peroxisome proliferator-activated receptor (PPAR): structure, mechanisms of activation and diverse functions

The structurally diverse xenobiotic peroxisome proliferators (PPs) increase the number of peroxisomes per cell and the levels of several enzymes, and cause hepatomegaly, often leading to hepatocarcinogenesis in a species- and tissue-specific manner. The deadlocked problems of the molecular mechanism of PP action and its physiological meanings have begun to be understood through cDNA cloning of a PP-activated receptor (PPAR). PPAR, a member of the steroid/thyroid/vitamin superfamily of nuclear receptors, has isoforms and differentially heterodimerizes with other nuclear receptors, providing potential mechanisms not only for species- and tissue-specific actions but also for diverse actions of PPs. Recent findings related to PPAR are summarized, and its possible role in lipid metabolism and involvement in PP-induced hepatocarcinogenesis are discussed.     

Biogenesis, cellular localization, and functional activation of the heat-stable enterotoxin receptor (guanylyl cyclase C)

Enterotoxigenic Escherichia coli elaborate a peptide called heat-stable enterotoxin (ST), which binds to and activates the intestinal ST receptor (STaR). STaR, also known as guanylyl cyclase C (GC-C), is a member of the transmembrane guanylyl cyclase receptor family. The mRNA for STaR encodes an approximately 120 kDa protein with the N-terminal ligand binding domain on the cell surface. Ligand affinity cross-linking studies have previously demonstrated several species of potential ST binding proteins, ranging in size from approximately 50 to 160 kDa. Although these smaller forms of STaR (50-80 kDa) have been proposed to act in vivo as toxin binding proteins, their biogenesis and localization have not previously been examined. Using pulse labeling in vivo and synchronized translation in vitro, we demonstrate that these smaller forms represent incomplete translational products and are not formed through limited proteolysis of the full-length receptor, as had previously been believed. We determined, using fluorescence confocal microscopy and surface labeling, that only approximately 25% of cellular receptors are expressed at the surface, while the remaining population is retained within the endoplasmic reticulum. Only full-length receptor is found at the surface of the cell, indicating this to be the biologically active form of STaR responsible for interacting with the heat-stable enterotoxin and other luminal intestinal peptides. The large intracellular receptor population, and potential for function before translocation to the cell surface, may impact on how pharmacologic modulators of this clinically important receptor are designed.     

Functional expression of a recombinant unitary glutamate receptor from Xenopus, which contains N-methyl-D-aspartate (NMDA) and non-NMDA receptor subunits

A cDNA encoding a 100-kDa subunit (XenNR1) of the N-methyl-D-aspartate (NMDA) glutamate receptor type has been cloned from Xenopus central nervous system. When XenNR1 is coexpressed in a mammalian cell line with a recently cloned 51-kDa non-NMDA receptor subunit (XenU1), also from Xenopus, it forms a functional unitary receptor exhibiting the pharmacological properties characteristic of both NMDA and non-NMDA receptors. Firstly, XenU1 can replace NR2 subunits, in complementing XenNR1 to introduce the ligand binding properties of a complete NMDA receptor. Second, responses to both NMDA and non-NMDA receptor agonists and antagonists were obtained in patch-clamp recordings from the cotransfected cells, but no significant responses were recorded when the cells were singly transfected. Third, from solubilized cell membranes from the cotransfected cells, an antibody to the NR1 subunit coprecipitated the binding sites of the non-NMDA receptor subunit. The unitary glutamate receptor has a unique set of properties that denote intersubunit interaction, including a glycine requirement for the responses to non-NMDA as well as to NMDA receptor agonists and voltage-dependent block by Mg2+ of the non-NMDA agonist responses.     

Free, autologous, skin transplantation in the horse

Seven pieces of autologous skin were transplanted onto freshly created, full thickness skin defects on the limbs and back of a one-year-old, male, piebald, Shetland pony. The transplantations were completed in two operative sessions, the transplants on the left side were done in the first session and the right side in the second. The sizes of the transplants varied from 20 sq cm to 2 sq cm and their thicknesses from whole skin to very thin, split skin. Donor sites were both rumps and the right side of the neck. Six of the seven grafts and two thirds of the remaining graft, were accepted. Both whole thickness transplants grew hair, whereas no hair growth was detected at the 26th and 16th week following surgery on the split thickness transplants placed on the left and right sides respectively. The full thickness donor sites healed by granulation, contraction and epithelialisation. Healing at the split skin donor sites was rapid and uneventfull, epithelialisation being completed within one week and hair growth manifest by one month.     

CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review)

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.     

Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo

There has been considerable interest in the potential role of growth factors in the initiation and development of cutaneous malignant melanoma (CMM). Platelet-derived growth factor (PDGF) has been shown to be secreted by melanoma cell lines and by metastatic melanoma in vivo. PDGF also has been reported to stimulate the development of tumour stroma and new blood vessels. We studied the expression of PDGF and its receptors by both immunohistochemistry (IHC) and in situ hybridization (ISH) in primary and metastatic melanoma and in normal skin specimens. Cryostat sections were incubated with 35S-labelled riboprobes and antibodies for PDGF-AA, PDGF-alpha receptor, PDGF-BB and PDGF-beta receptor. Both primary and metastatic melanoma exhibited significant expression of PDGF-AA, PDGF-BB and PDGF-alpha receptor by both IHC and ISH, compared with only background expression in normal skin. We did not observe expression of PDGF-beta receptor in melanoma. Our results suggest that PDGF may function as an autocrine growth factor, as well as an angiogenesis factor, in CMM tumour development. This expression of the PDGF-alpha receptor rather than the beta receptor may be unique among solid tumours.