Fine mapping of a quantitative trait locus for osteochondrosis on horse chromosome 2.

In this study, we refine a quantitative trait locus for equine osteochondrosis (OC) on horse chromosome (ECA) 2 to a genome-wide significant interval at 20.08-30.94 Mb. The marker set contained 27 newly developed microsatellites equidistantly distributed over ECA2 and 44 nucleotide polymorphisms, located in 16 positional candidate genes for OC. Genotyping was performed in 211 Hanoverian horses from 14 paternal half-sib groups. A NCDN-associated SNP and haplotype were significantly associated with OC in fetlock and/or hock joints. This study is a further step towards the identification of genes responsible for OC in horses.

Refinement of a quantitative trait locus on equine chromosome 5 responsible for fetlock osteochondrosis in Hanoverian warmblood horses.

In this report, we provide 29 new informative microsatellites distributed over a region of 21 Mb on horse chromosome (ECA) 5 and refine a quantitative trait locus (QTL) for fetlock osteochondrosis dissecans (OCD) to a genome-wide significant interval between 78.03 and 90.23 Mb on ECA5. Genotyping was performed in 211 Hanoverian warmblood horses from 14 paternal half-sib groups. Within this OCD-QTL, collagen type XXIV alpha 1 was identified as a potential functional candidate gene for equine osteochondrosis. This report is a further step towards unravelling the genes that cause equine osteochondrosis.

Monoclonal antibody-defined human pancreatic cancer-associated antigens.

Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

Body weight distribution and organ size in newborn swine (sus scrofa domestica) -- a study describing an animal model for asymmetrical intrauterine growth retardation.

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

[Iodine and thyroid hormone status of mother pigs and their offspring]. / Zum Jod- und Schilddrüsenhormonstatus von Mutterschweinen und ihren Nachkommen.

The iodine concentration in the chain sow feed-->blood serum of dams-->milk-->blood serum of piglets (2 per litter) was determined in 36 litters in two experiments with different dietary iodine levels and in 16 litters in the framework of field studies in two piglet production farms in each case at weaning after four weeks lactation. In the blood serum also the concentration of thyroxine (T4) and triiodothyronine was determined. The serum concentration of iodine and T4 did not indicate dietary iodine administration (sows) or showed only a weak response (piglets). The iodine concentration of milk was very strongly affected by iodine administration and by the iodine status of sows prior to the experiments. The highest milk iodine concentration was found in the sows of piglet production farms, corresponding to the level of iodine administered. For diagnosis of the iodine supply status the iodine concentration of sow milk should be analyzed. The lower limit of milk iodine concentration is presently defined as 50 micrograms/l, and the mean of 5 random samples per sow herd should not fall below this limit. Serum concentrations of iodine and T4 may remain moderate even in case of a low iodine supply (sow serum: 30 micrograms iodine/l, 25 nmol T4/l; piglet's serum: 50 micrograms iodine/l, 55 nmol T4/l), and are unsuited for diagnosis of iodine status.

Refinement of a quantitative gene locus on equine chromosome 16 responsible for osteochondrosis in Hanoverian warmblood horses.

Osteochondrosis (OC) is an inherited developmental disease in young horses most frequently observed in thoroughbreds, trotters, warmblood and coldblood horses. Quantitative trait loci (QTL) for equine OC have been identified in Hanoverian warmblood horses employing a whole genome scan with microsatellites. A QTL on ECA16 reached the genome-wide significance level for hock osteochondrosis dissecans (OCD). The aim of this study was to refine this QTL on ECA16 using an extended marker set of 34 newly developed microsatellites and 15 single nucleotide polymorphisms (SNPs). We used the same 14 paternal half-sib groups as in the above-mentioned whole genome scan. The QTL for OCD in hock joints on ECA16 could be delimited at an interval between 17.60 and 45.18 Mb using multipoint non-parametric linkage analyses. In addition, six microsatellites and one SNP were significantly associated with hock OCD in the QTL region between 24.26 and 42.41 Mb. Furthermore, our analysis revealed a second QTL for fetlock OC between 6.55 and 24.26 Mb on ECA16. This report is a further step towards unravelling the genes underlying QTL for equine OC and towards the development of a marker test for OC in Hanoverian warmblood horses.

Identification of a new quantitative trait locus on equine chromosome 18 responsible for osteochondrosis in Hanoverian warmblood horses.

In this study we present a newly detected QTL associated with osteochondrosis in Hanoverian warmblood horses on equine chromosome 18 (ECA18). We developed a highly polymorphic and evenly distributed marker set on ECA18 employing the horse genome assembly EquCab2. The marker set included 11 newly developed microsatellites. Average polymorphism information content was 62.1% at an average spacing of 3 Mb. For genotyping of this marker set comprising a total of 27 highly polymorphic microsatellites, we used the same 14 paternal half-sib families as in the previous whole genome scan. The chromosome-wide linkage analysis revealed a QTL for osteochondrosis in fetlock, hock, or both joints, as well as for osteochondrosis dissecans in hock joints between 74.94 and 82.25 Mb. Within this QTL for equine osteochondrosis, the parathyroid hormone 2 receptor gene could be identified as a positional candidate gene. This report is a further step toward the identification of genes responsible for osteochondrosis in horses.

Altered renal function in growth-restricted newborn piglets.

The effect of intrauterine growth restriction (IUGR) on renal hemodynamics and excretory functions was studied in 76 newborn piglets 12-27 h old. The experiments were performed on anesthetized animals divided into normal-weight piglets and IUGR piglets according to their birth weight. The "normal-weight" category included animals with a birth weight >40th percentile (piglets heavier than 1,220 g); the IUGR category included animals with a birth weight >5th and <10th percentiles (piglets with a birth weight between 733 g and 853 g). Cardiac output and renal blood flow were measured by the colored microsphere technique. Urine was collected from catheters placed in the ureters. This animal model of naturally occurring growth retardation in swine gives asymmetric growth with an increase in the mean ratio of brain weight to liver weight from 1.02 to 1.85 (P<0.01). Thus there was only a small reduction in brain weight (11%). In contrast, the reduction in the weight of liver (50%) and kidney (46%) was proportional to that in body weight (46%). Heart rate, cardiac output, arterial blood gases, and pH were similar in normal-weight and IUGR piglets, but arterial blood pressure and arterial glucose content were significantly reduced in IUGR piglets (P<0.01). Moreover, IUGR piglets had higher plasma catecholamine levels (P<0.05). Renal blood flow and renal vascular resistance were similar in the normal-weight and in the IUGR groups. However, in IUGR animals, glomerular filtration rate was significantly less than in the controls (P<0.05). Normal-weight and IUGR newborn piglets reabsorbed sodium very efficiently, the fractional sodium excretion was less than 1% in both groups. We conclude that renal blood flow is maintained in relation to kidney and body weight in IUGR newborns, but that important renal excretory functions are compromised due to IUGR.

Restricted cardiovascular and cerebral performance of intra-uterine growth retarded newborn piglets during severe hypoxia.

In 7 term born two-day-old intra-uterine growth retarded (IUGR) piglets cardio- and cerebrovascular, metabolic and EEG reactions were studied at rest and during severe hypoxia in comparison to 17 normal-weight piglets. In IUGR piglets even in control conditions a distinct cerebral blood flow (CBF) elevation, lower cerebrovascular resistance and oxygen consumption in the higher perfused brain regions at diminished arterial blood pressure were observed. Also the arterial glucose concentration was in the borderline hypoglycemic range, however, cerebral glucose delivery was nearly maintained. IUGR piglets survived a 1-h hypoxic period (paO2 = 25-30 mmHg) less frequently. The main reason was the distinctly restricted emergency reaction with a lack of arterial blood pressure increase and blood glucose elevation as well as a reduced (higher perfused brain regions) or absent CBF increase (lower perfused brain regions). Thereby, even in the early stage of hypoxia cerebral oxygen delivery in both brain compartments and oxygen consumption in the latter were decreased followed by a further decrease of the arterial blood pressure. The latter factor was essential for acute cardio-vascular-cerebral insufficiency.

Interaction between systemic circulation and brain injuries in newborns.

In several studies different pathogenetic mechanisms of metabolic and/or cardiovascular origin were shown depending on the type of hypoxic or hypoxic/hypercapnic stress and conditions of animals (normal developed or intrauterine growth retarded newborn piglets). Thus, in normal-weight piglets the prevention of compensatory hyperventilation owing to severe hypoxia (artificially ventilated animals) leads to critical, i.e. lethal acidosis. In intrauterine growth retarded piglets, a severe hypoxia cannot be vitally compensated because of the restricted circulatory centralization. Moreover, a limited cerebrovascular dilatation during moderate hypoxia/hypercapnia produces a critical state of the metabolic supply in those animals.