Biomedical subjects

T A Niewold

Publications and source records attributed to T A Niewold.

At least 37 records · Page 2Linked to original sources

PubMed2001

Thirty minutes transport causes small intestinal acidosis in pigs.

Long duration (>10 hours) transport has been described as having either adverse or no effects on porcine health. However, the effect of short duration transport on porcine health is unknown. In the present paper, pigs fed ad libitum (n = 6) were transported for 30 minutes, anaesthetised, instrumented, and cardiovascular and gastrointestinal parameters were measured. Non-transported pigs (n = 6) served as controls. No significant differences between groups were found concerning blood flow in the arteria mesenterica cranialis, heart rate, cardiac output, pulmonal blood pressure, haemoglobin content and haematocrit value. Systolic systemic blood pressure was higher (though not significant), and diastolic systemic blood pressure was significantly higher in the transported pigs than in the controls. Small intestinal pH was significantly lower in transported pigs than in control pigs. We conclude that a 30-minute transport of fed pigs results in small intestinal acidosis. As small intestinal acidosis predisposes to bacterial translocation, even short duration transport should be avoided when possible.

Acidosis↗

PubMed2001

Oedema disease is associated with metabolic acidosis and small intestinal acidosis.

Limited information is available about the pathogenesis and pathophysiology of oedema disease (OD). Oedema disease is caused by specific enterotoxemic Escherichia coli (SLTIIv-toxin producing) strains; however, the same strains are also found in non-afflicted pigs. Furthermore, it is unclear how the 80 kDa SLTIIv-toxin can pass the intestinal barrier. In the present paper, piglets showing signs of acute OD were anaesthetised, instrumented and cardiovascular and intestinal parameters were determined at 0, 1, 2 and 3 hours. Healthy piglets from the same herd were used as a control. Cardiac output, blood pH and bicarbonate, small intestinal intramucosal pH, and (pulmonary) blood pressure were significantly lower in OD-pigs than in control pigs. It is concluded that OD is associated with metabolic and intestinal acidosis. Intestinal acidosis is known to increase macromolecular permeability. This suggests that once OD has developed, influx of SLTIIv-toxin into the blood stream is facilitated, thus perpetuating the disease. Since intestinal permeability appears to be central in OD, it is argued that post-weaning events increase intestinal permeability and predispose individuals to OD.

Acidosis↗

PubMed2001

Small intestinal morphology in weaned piglets fed a diet containing spray-dried porcine plasma.

The hypothesis tested in this study was that the reported beneficial effects of spray-dried porcine plasma (SDPP) on piglet post-weaning performance and health are associated with a trophic effect on small intestinal mucosa. At 24 days of age, the piglets of seven sows were assigned to one of three treatment groups. One group continued to be suckled. The other two groups were weaned and offered a diet containing either 15 per cent SDPP or casein. From each treatment group, one piglet was anaesthetised and samples were taken from the small intestinal wall at 26, 28 and 31 days of age. There were no significant effects of SDPP versus casein on villus length. On average, there was less mitotic activity in the SDPP -fed piglets than in those fed casein on days 4 and 7 after weaning. As less mitotic activity leads to less immature enterocytes, this may provide a mechanism for the reported beneficial effects of SDPP on performance and health.

Animal Feed↗

PubMed2000

Llama heavy-chain V regions consist of at least four distinct subfamilies revealing novel sequence features.

In addition to conventional antibodies (Abs), camelids possess Abs consisting of only heavy chains. The variable domain of such a heavy-chain Ab (VHH) is fully capable of antigen (Ag) binding. Earlier analysis of 47 VHHs showed sequence features unique to VHH domains. These include the presence of characteristic amino acid substitutions in positions which, in conventional VH domains are involved in interdomain interactions, and the presence of a long third complementarity-determining region (CDR3) which is frequently constrained by an interloop disulphide bond. Here, we describe a large (152) set of Lama glama VHH cDNAs. Based on amino acid sequence similarity, these and other published camelid VHHs were classified into four subfamilies. Three subfamilies are absent in dromedaries, which have been the primary source of VHHs thus far. Comparison of these subfamilies to conventional VH regions reveals new features characteristic of VHHs and shows that many features earlier regarded as characteristic of VHHs in general are actually subfamily specific. A long CDR3 with a concomitant putative additional disulphide bond is only observed in two VHH subfamilies. Furthermore, we identified new VHH-characteristic residues at positions forming interdomain sites in conventional VH domains. The VHH subfamilies also differ from each other and conventional VH domains in the canonical structure of CDR1 and CDR2, mean CDR3 length, and amino acid residue variability. Since different VHH-characteristic residues are observed in all four subfamilies, these subfamilies must have evolved independently from classical VH domains.

Amino Acid Sequence↗

PubMed2000

A review of porcine pathophysiology: a different approach to disease.

Diseases are often thought to result from a single cause. Although this is sometimes the case, e.g. with a highly virulent infection such as Classical Swine Fever (CSF), more often clinical disease in swine herds results from multiple predisposing factors. This is especially true in modern intensive pig husbandry, in which the role of highly infectious diseases is limited to (nonetheless devastating) outbreaks. More important nowadays are diseases, although associated with an agent, without a clear pathogenesis. The emphasis in disease control thus far has been on treatment, eradication and prevention. This has been achieved by focusing attention on husbandry factors, such as climate, housing, hygiene, management, and nutrition. Although this approach has been successful for a number of diseases, several health problems are persistent. There are strong indications that in the latter, intrinsic animal factors are important. Successful handling of these problems requires knowledge of the (patho)physiology of the pig. In this article, several characteristics of pig physiology associated with the occurrence of disease are described. It appears that the modern (fattening) pig is exceptional among other animal species in that its cardiovascular system is mismatched to its body weight. It is argued that this particular disposition causes relatively minor disturbances to have major consequences in the pig. This concept of pig physiology is central to the understanding of the hitherto poorly understood pathogenesis of several diseases, such as oedema disease.

Animal Husbandry↗

PubMed1999

Effects of enrofloxacin on porcine phagocytic function.

The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 microg/ml. Enrofloxacin (0.5 microg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5x the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida, and similar intra- and extracellular reductions of P. multocida isolates by enrofloxacin were found. Intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin at 5x the MIC in both PMNs and AMs. AMs are very susceptible to the A. pleuropneumoniae cytotoxin. This suggests that in serologically naive pigs the enhancing effect of enrofloxacin on the bactericidal action of PMNs may have clinical relevance.

Actinobacillus pleuropneumoniae↗

PubMed1999

Familial amyloidosis in cats: Siamese and Abyssinian AA proteins differ in primary sequence and pattern of deposition.

Familial AA amyloidosis is a hereditary trait in Abyssinian cats, with the kidney as the main target organ. The amino acid sequence of the amyloid A protein of the Abyssinian cat has been described earlier. Recently, familial amyloidosis has been found in Siamese cats, with the liver as the main target organ. In the present paper, we describe the complete amino amid sequence of the major constituent protein, of two Siamese cats. Siamese hepatic protein AA showed homology with, but was different from all feline SAA and AA sequences hitherto reported. Two substitutions (46Q-R and 52A-V) from the Abyssinian protein sequence were identified, one of which (46Q-R) is a non-homologous substitution not found in mammalian SAA, but is present in two bird AA amyloid proteins. This shows the presence of an unique amyloidogenic SAA isotype in Siamese cats. Both the Siamese and the Abyssinian sequence are amyloidogenic, thus making identification of amyloidogenic residues difficult. Apart from the apparent inherent amyloidogenicity of SAA, it can not be excluded that certain amino acid substitutions could enhance its amyloidogenicity but also could contribute to tissue predilection in amyloidosis.

Amino Acid Sequence↗

PubMed1999

Casein related amyloid, characterization of a new and unique amyloid protein isolated from bovine corpora amylacea.

Amyloid bodies can be found in mammary secretory tissue of various species. These corpora amylacea (CA) have a lamellated structure, contain amyloid fibrils and are predominantly located in the alveolar lumina. The nature of the amyloid was not known, but CA were suggested to originate either from milk casein or mammary alveolar epithelial keratin. In the present report, bovine CA were analyzed histochemically. Furthermore, CA were isolated, analyzed and the amyloid was purified and characterized by amino acid sequencing. CA amyloid appeared to be potassium permanganate sensitive and tryptophan positive, and in this respect different from most other amyloid types except for AA and beta-2 microglobulin amyloid. Gel filtration of purified amyloid fibrils showed a HMW peak and a major 4 kD peak. N-terminal amino acid sequencing showed the amyloid to consist of tryptic-like peptides with an unusually high content of amino acids with bulky side chains. The amyloid protein was identified as derived from alpha-S2-casein. The fragments are of varying length (32, 33 and 45 amino acids), but all start at position 81 of alpha-S2-casein. We have identified a new and unique amyloid protein, and we propose to designate it as A alpha-S2C according to the guidelines for amyloid nomenclature.

Amino Acid Sequence↗

PubMed1997

Generalized AA-amyloidosis in Siamese and Oriental cats.

During a 7 year period (1987-1994), 194 Siamese cats including a colour variant designated Oriental cat, were presented for post-mortem examination. Twelve of these animals (6.2%) were diagnosed with amyloidosis. Major gross pathological findings included enlarged pale livers with haemorrhages, pale and swollen spleens, and dilated intestines. Deposits of amyloid were found in these tissues. The amyloid was found to cross-react with anti dog AA-antiserum when examined with peroxidase antiperoxidase (PAP) staining (four cases). Amyloid fibrils were purified by the water extraction method and its major constituting protein (AA) was isolated by gel filtration. Amino acid sequence analysis of this protein from a Siamese cat and an Abyssinian cat revealed a significant difference between these breeds. In the Siamese protein AA two amino acid substitutions (46 R for Q and 52 V for A) were encountered. This finding indicates the existence of a new feline amyloid A protein occurring in the Siamese breed which differs from presently known (apoS)AA-proteins. Additionally, the pedigree analysis of affected cats suggests a familial trait.

Amino Acid Sequence↗

PubMed1996

Characterization of a light chain product of the human JC lambda 7 gene complex.

The human light chain JC lambda locus is comprised of seven distinct segments, designated JC lambda 1, JC lambda 2, JC lambda 3, JC lambda 4, JC lambda 5, JC lambda 6, and JC lambda 7. Whereas three of these seven represent pseudogenes (psi Clambda 4, psi C lambda 5, and psi C lambda 6), the JC lambda 1, JC lambda 2, and JC lambda 3 complexes are functional, as demonstrated by the finding of their protein products through sequence analyses of lambda-type Bence Jones proteins and light chains derived from monoclonal Igs. Although the JC lambda 7 segment also appears functional, as evidenced through analysis of lymphocyte-derived mRNA, heretofore no monoclonal JC lambda 7-containing lambda-chains have been identified. Serologically, two distinct isotypic markers, Mcg and Oz, are associated, respectively, with JC lambda 1 and JC lambda 3 proteins, in contrast to JC lambda2 components, which do not express these determinants and represent a third isotype. Although another serologic marker, Ke (Kern), considered a fourth isotype, has been assigned to the JC lambda 7 complex, this relationship has been questioned. We now report the primary structural features of a lambda-type Bence Jones protein that include the four distinctive residues encoded by the JC lambda 7 gene segment. This protein, obtained from a patient with multiple myeloma and designated MCP, represents the first example of such a molecule and provides definitive evidence that the JC lambda 7 gene complex is functional. Additionally, comparison of the C lambda sequences of Mcg-/Oz- Bence Jones proteins MCP and KERN supports the contention that the Ke-associated one-residue amino acid variation at position 152 reflects a C lambda A2 polymorphism and that yet another isotypic marker, provisionally designated Mcp, is encoded by the JC lambda 7 gene segment. Thus, we posit that there are four human JC lambda isotypes, Mcg, Ke-Oz-/Ke+Oz-, Ke-Oz+, and Mcp, that represent, respectively, products of the JC lambda 1, JC lambda 2, JC lambda 3, and JC lambda 7 gene complexes.

Adult↗

PubMed1995

Influence of physical stress on the plasma concentration of serum amyloid-A (SAA) and haptoglobin (Hp) in calves.

The influence of physical stress on the plasma concentration of the acute-phase proteins serum amyloid-A (SAA) and haptoglobin (Hp) was studied in 10 calves. Two different stress levels were created by housing two groups of five calves, each on different types of floor. The stress level was assessed by studying videotapes of the animals, and, subsequently, by quantifying the problems related with moving across the pens and the time the calves spent lying down and standing. Plasma concentrations of Hp, SAA, aldolase, and cortisol were measured in blood samples obtained by jugular venepuncture. Plasma SAA concentrations were significantly (p < 0.001) elevated in animals housed on the floor type associated with the highest level of physical stress, although the concentrations were within the normal range for healthy adult cattle. Hp concentrations were not elevated. The floor type did not alter the stress related biochemical variables aldolase and cortisol. It is concluded that plasma SAA concentrations rise upon physical stress, whereas Hp concentrations do not change. The absence of a significant difference in aldolase or cortisol concentrations indicates that the difference in the level of neuro-endocrine stress between the animals housed on the two floor types is only minimal. Consequently, SAA is suggested to be a sensitive variable to assess physical welfare in calves.

Animal Husbandry↗

PubMed1995

First evidence for the existence of multiple isoforms of bovine serum amyloid-A (apoSAA).

Bovine serum amyloid-A (SAA) was purified from acute-phase high density lipoprotein (HDL) by affinity chromatography and subsequent gel filtration chromatography. The identity of the isolated protein was checked by Western blotting following SDS-urea-PAGE using antisera raised against the purified protein fraction (SAA) and Amyloid A (AA). The antiserum raised against the purified SAA stained Congo red positive regions in the kidney of an AA-amyloidotic cow and reacted on Western blot with an AA-related protein of approximately 14 kDa. Moreover, it immunostained two to three bands, of approximately 14 kDa, present in serum from diseased cows, proportionally to the serum SAA concentration as measured by ELISA. Isoelectric focusing of the purified bovine SAA fraction revealed three major (pI 5.5, 6.0, 6.4) and three minor (pI 4.8, 5.0, 7.3) isoforms and two-dimensional SDS-urea-PAGE confirmed the identity of the major isoforms. Isoelectric focusing of SAA isolated from sera, obtained from cows affected with different diseases, showed a variable ratio of the isoforms. In SAA isolated from serum obtained from a cow suffering from spontaneous AA-amyloidosis only one isoform (pI 4.8) was detectable. It is concluded that the results give first evidence for the existence of multiple isoforms of bovine SAA, occurring in different plasma concentration ratios during different diseases.

Animals↗

PubMed1995

Effect of exercise and food restriction on selected markers of the acute phase response in hamsters.

Acute aerobic exercise has been shown to elicit physiological changes characteristic of the acute phase response (APR), a nonspecific host defense response. Regular evocation of these changes may prime the immune system to improve resistance to disease. Because food deprivation is associated with an impaired APR, food restriction may prevent these beneficial changes. We tested the hypotheses that voluntary exercise elicits an APR and that food restriction modifies this response in four groups of hamsters: ad libitum-fed sedentary, ad libitum-fed exercised, food-restricted sedentary, and food-restricted exercised. Five variables altered during an APR were examined: core temperature, serum iron, serum interleukin-6, serum amyloid A, and serum glucocorticoids measured by biotelemetry, colorimetric analysis, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, and radioimmunoassay, respectively. Blood was drawn during the hamsters' inactive period after 19-20 days of access to running wheels. Resting core temperature was elevated by exercise and depressed by food restriction (P < 0.01). Iron was depressed by food restriction (P < 0.01). Cortisol, but not corticosterone, was elevated by food restriction (P < 0.001). There were no significant differences among groups in interleukin-6 (P > 0.49) or serum amyloid A (P > 0.29). We conclude that there is little evidence that voluntary exercise or exercise combined with food restriction causes an APR in hamsters.

Acute-Phase Reaction↗

PubMed1994

Hamster hepatic amyloid A (AA) protein is derived from a novel member of the SAA gene family.

The nearly complete amino acid sequence of casein-induced hepatic hamster AA is described. Hamster AA appeared to be C-terminally ragged as found in other species. Furthermore, the N-terminus was (partially) truncated. Hamster hepatic AA sequence showed high homology with, but was not identical to hamster SAA-isotype sequences deduced earlier from mRNA in hepatic and extra-hepatic tissue. Therefore, hamster hepatic AA is derived from a novel member of the SAA gene family. However, the origin of hepatic AA-amyloid remains unclear.

Amino Acid Sequence↗

PubMed1993

Gastrointestinal AAPOAII and systemic AA-amyloidosis in aged C57BL/Ka mice. Amyloid-type dependent effect of long-term immunosuppressive treatment.

The light microscopic and immunohistochemical features of a novel localized senile amyloidosis in the gastrointestinal tract of C57BL/Ka mice are described. Senile gastrointestinal amyloidosis was predominantly found in the lamina propria of the ileum, cecum and stomach and infrequently in other segments of the gastrointestinal tract. The Congo red affinity of the senile amyloid was sensitive to potassium permanganate pretreatment. The amyloid did not react with anti-AA and anti-immunoglobulin antisera, but stained positively for apoAII, a major apolipoprotein of high density lipoproteins. A similar type of amyloid, termed AApoAII, has recently been described in a systemic form of senile amyloidosis in mice. In the present study, we investigated the effect of long-term immunosuppressive treatment on the incidence of systemic AA-amyloidosis and gastrointestinal AApoAII-amyloidosis in aged C57BL/Ka mice. Gastrointestinal amyloidosis occurred in 60% of the control mice, but significantly less in mice of the immunosuppressed groups. In contrast, systemic AA-immunoreactive amyloidosis was only found in mice that were given immunosuppressive treatment. There was no codeposition of AA and AApoAII-amyloid. These findings indicate that immunosuppressive drugs have a profound effect on the incidence as well as the type of amyloidosis in C57BL/Ka mice.

Aging↗

PubMed1993

Recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and rhTNF-alpha analogue enhance amyloid deposition in the Syrian hamster.

Tumour necrosis factor-alpha (TNF-alpha) is one of the cytokines that stimulate the production of serum amyloid A (SAA), the precursor of AA amyloid. The role of TNF-alpha in amyloidogenesis was investigated in experimental hamsters using purified recombinant human TNF-alpha (rhTNF-alpha) and rhTNF-alpha analogue different from the normal molecule by two amino acid substitutions. Daily injections of 1 microgram rhTNF-alpha resulted in elevated SAA levels but even in the presence of amyloid enhancing factor (AEF) no amyloid was deposited, indicating that apart from the AEF and one particular SAA stimulating factor an additional factor is needed to result in amyloid deposition. This factor is generated by repeated injections of E. coli lipopolysaccharide (LPS). A single intraperitoneal injection of 12.5 micrograms or more of rhTNF-alpha followed by seven daily subcutaneous injections of LPS resulted in enhanced amyloid deposition. Heat denaturation of rhTNF-alpha did abolish its AEF activity. The rhTNF-alpha analogue, having one-fifth of the cytotoxic activity of the normal rhTNF-alpha, showed a similar reduction in its SAA-inducing capacity and its amyloidogenicity. This suggests the AEF activity to be closely related to TNF-alpha activity. However, poly(I)-poly(C) (a potent inducer of IL-6) also showed AEF activity, suggesting that not a single cytokine but rather a certain combination of different cytokines could be decisive in AA amyloidogenesis.

Amyloid↗

PubMed1992

Failure of adrenocorticotrophic hormone to release serum amyloid A in cattle.

The objective of this study was to determine whether adrenocorticotrophic hormone plays a direct role in the secretion of serum amyloid A (SAA) in cattle. Seven lactating Holstein-Friesian cows were given either saline or 25 iu adrenocorticotrophic hormone (ACTH) intravenously at 09.00 in a two factor crossover design. Plasma cortisol concentrations had increased significantly by one hour after the injection of ACTH, whereas the SAA level had not increased by 24 hours after injection. It is concluded that in cattle adrenocorticotrophic hormone has no direct influence on the release of SAA by the hepatocyte.

Adrenocorticotropic Hormone↗

PubMed1991

Characterization of proteoglycans and glycosaminoglycans in bovine renal AA-type amyloidosis.

Highly sulfated glycosaminoglycans (GAG) or proteoglycans (PG), especially heparan sulfate (HS) and heparan sulfate proteoglycan (HSPG), are considered to be intimately associated with amyloid deposits in different types of amyloidosis. Based on this relationship an important role for HS has been suggested in amyloidogenesis. The present immunohistological and ultrastructural study shows that in bovine renal AA-amyloidosis, sulfated GAG/PG was not restricted to amyloid deposits proper and that areas without GAP/PG were also present within the amyloid. Both glomerular and papillary amyloid contained HS (PG), and the latter also contained chondroitin sulfate (CS) and dermatan sulfate (DS), suggesting a correlation between the location of the amyloid and the type of GAG/PG deposited. Amyloid P component (AP) had a distribution similar to that of HSPG, confirming their affinity-based relationship. The GAG types found ultrastructurally in amyloid fibril preparations of glomerular and papillary amyloid isolated from the same kidney, reflected the immunohistological findings. HS was shown to be the predominant GAG in all papillary amyloid fibril extracts. Taking into account the chemico-physical properties of HS, it cannot be excluded that this predominance is introduced by the purification procedure. These results suggest that the association of GAG/PG and amyloid is not necessarily mutually obligatory and that the proposed importance of GAG in amyloidogenesis is disputable.

Amyloidosis↗