Biomedical subjects
Publications and source records attributed to M Jacobson.
The occurrence of Brachyspira species and Lawsonia intracellularis was investigated by PCR analyses of faeces from 60 children living on European pig farms. In addition, 60 other children were included as controls. Two samples were positive for B. aalborgi but B. pilosicoli and L. intracellularis were not demonstrated.
The development of intestinal lesions after inoculation with Brachyspira hyodysenteriae was followed by repeated endoscopy and biopsy sampling through a caecal cannula. Seven eight-week-old pigs were cannulated and inoculated, two were cannulated but not inoculated, and two pigs were inoculated but not cannulated. Endoscopy, biopsy, and blood sampling to determine SAA (serum amyloid A), haptoglobin, cortisol, and WBC counts were performed at scheduled time-points. At the third day of disease, endoscopy showed a hyperaemic, perturbed mucosa and excessive amount of mucus. Histologically, crypt hyperplasia, depletion of goblet cell mucus, and erosions were noted. Simultaneously, elevated acute phase proteins and circulating monocytes, and decreased number of intraepithelial CD3(+) cells were observed. After five days the pigs recovered. Intestinal lesions were demarcated and interspersed among apparently normal mucosa and blood parameters returned to initial values. Endoscopy through an intestinal cannula made it possible to follow the development of intestinal alterations in vivo and describe the sequential events during the course of swine dysentery. The number of animals used in a study could thus be minimised and the precision of the experiment increased.
1. Streptozotocin (STZ)-induced diabetic cardiomyopathy is frequently associated with depressed diastolic/systolic function and altered heart rhythm. 2. The effects of insulin treatment on heart rhythm, body temperature and physical activity in STZ-induced diabetic rats were investigated using biotelemetry techniques. 3. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar - Lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded with a telemetry system for 10 days before STZ treatment, for 20 days following administration of STZ (60 mg/kg) and thereafter, for 30 days while rats received daily insulin. 4. Heart rate, physical activity and body temperature declined rapidly 3-5 days after administration of STZ. Pre-STZ heart rate was 362 +/- 7 b.p.m., falling to 266 +/- 12 b.p.m. 5-15 days after STZ with significant recovery to 303 +/- 14 b.p.m. 10-20 days after commencement of insulin. Pre-STZ body temperature was 37.5 +/- 0.1C, falling to 37.2 +/- 0.2C 5-15 days after STZ with significant recovery to 37.5 +/- 0.1C 10-20 days after commencement of insulin. Physical activity and heart rate variability were also reduced after STZ but there was no significant recovery during insulin replacement. 5. Defective autonomic regulation and/or mechanisms of control that are intrinsic to the heart may underlie disturbances in heart rhythm in the STZ-induced diabetic rat.
The objective of this work was to evaluate the physiological and behavioural effects of opioid analgesic treatment in pigs subjected to abdominal surgery. Ten Swedish Landrace x Yorkshire pigs (20 +/- 4 kg b.w.) were submitted for intestinal cannulation. The pigs were allocated into two groups during one preoperative, one surgical and two postoperative days. All pigs were anaesthetized with medetomidine, tiletamine and zolazepam. One group was treated with epidural morphine (0.1 mg/kg) preoperatively, and transdermal fentanyl patches (50 microg/kg/h) were applied behind the ear immediately after surgery. The other group received epidural saline (equivalent volume) and placebo patches. All pigs were regularly weighed and clinically examined and repeated blood samples were analysed for serum concentrations of cortisol, beta-endorphin and fentanyl. Pre- and postoperative behaviours were evaluated by a swine specialist blinded to the treatment, three times a day, and were also videotape recorded for a total of 84 h per pig. No differences in behaviour were noted by the observer. During the first postoperative 12 h, treated pigs did not differ in activity compared with preoperative recordings, while untreated pigs were found to be less active. The treated group started to show interest in eating immediately after anaesthesia recovery, whereas the placebo group did not. During the 12-60 h postoperative period, the treated group had lower activity levels compared with the preoperative levels, which were similar to those in the placebo group. Treated pigs gained 0.5 +/- 0.2 kg during the subsequent two postoperative days, whereas the untreated pigs lost weight throughout the experiment. Cortisol concentration differed immediately after the surgery: Group P had 325 +/- 120 nmol/L and Group M 159 +/- 49 nmol/L. beta-endorphin concentration did not differ between groups. The highest serum fentanyl concentration (0.37 +/- 0.3 ng/mL) was measured 24 h postoperatively. Preoperative epidural morphine in combination with postoperative transdermal fentanyl resulted in earlier return to normal activity levels and an immediate weight gain after surgery.
In vivo biotelemetry studies have demonstrated that short-term streptozotocin (STZ)-induced diabetes is associated with a reduction in heart rate (HR) and heart rate variability (HRV) and prolongation of QT and QRS intervals. This study investigates the long-term effects of STZ-induced diabetes on the electrocardiogram (ECG), physical activity and body temperature. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. ECG, physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg(-1)) for a period of 22 weeks. HR, physical activity and body temperature declined rapidly 3-5 days after the administration of STZ. The effects became conspicuous with time reaching a new steady state approximately 1-2 weeks after STZ treatment. HR at 4 weeks was 268 +/- 5 beats min(-1) in diabetic rats compared to 347 +/- 12 beats min(-1) in age-matched controls. HRV at 4 weeks was also significantly reduced after STZ treatment (18 +/- 3 beats min(-1)) compared to controls (33 +/- 3 beats min(-1)). HR and HRV were not additionally altered in either diabetic rats (266 +/- 5 and 20 +/- 4 beats min(-1)) or age-matched controls (316 +/- 6 and 25 +/- 4 beats min(-1)) at 22 weeks. Reduced physical activity and/or body temperature may partly underlie the reductions in HR and HRV. In addition, the increased power spectral low frequency/high frequency ratio from 4 weeks after STZ treatment may indicate an accompanying disturbance in sympathovagal balance.
A variety of contractility defects have been reported in the streptozotocin (STZ)-induced diabetic rat heart including alterations to the amplitude and time course of cardiac muscle contraction. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram (ECG), physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg-1). Heart rate (HR), physical activity and body temperature declined rapidly 3-5 days after administration of STZ. The effects became more conspicuous with time and reached a new steady state approximately 10 days after STZ treatment when HR was 255+/-8 beats min-1 in diabetic rats compared to 348+/-17 beats min-1 in age-matched controls. Heart rate variability (HRV) was also significantly reduced after STZ treatment (18+/-3 beats min-1) compared to controls (36+/-3 beats min-1). Reduced physical activity and/or body temperature may partly underlie the reduction in HR and HRV. Reductions in power spectral density at higher frequencies (2.5-3.5 Hz) suggest that parasympathetic drive to the heart may be altered during the early stages of STZ-induced diabetes. Short-term diabetes-induced changes in vital signs can be effectively tracked by continuous recording using a telemetry system.
The aim of the present study was to survey the prevalences of the enteric pathogens Brachyspira hyodysenteriae, Brachyspira pilosicoli and Lawsonia intracellularis in Swedish growing pigs and in the Swedish wild boar population and to relate these findings to clinical signs. The study included 105 randomly selected herds, constituting approximately one third of Swedish herds with a herd size of >100 sows. The herds were located all over the country. In these herds, growth promoters were not used and pigs sampled were not subjected to any medication. From each herd, samples were taken from 10 growing pigs aged 8-12 weeks, corresponding to approximately 2.5% of all growing pigs present in the herd at the sampling occasion. If possible, the samples were taken from pigs with diarrhoea. Forty-eight faecal samples and 71 rectal swabs were also taken from free-living wild boars (31 piglets, 19 growers and 21 adult animals) at shooting. The samples were analysed by culture and biochemical tests for the presence of Brachyspira spp. and by nested PCR for the presence of L. intracellularis. Brachyspira hyodysenteriae was not demonstrated in any sample. Brachyspira intermedia was detected in 22 samples originating from 15 herds, Brachyspira innocens/Brachyspira murdochii was detected in 370 samples from 82 herds and B. pilosicoli was detected in 134 samples originating from 34 herds. In 21 herds and in 534 samples, no Brachyspira spp. were detected. Lawsonia intracellularis was demonstrated in 285 samples from 50 herds. Further, 418 samples from conventional herds were negative with respect to L. intracellularis and in 345 samples the PCR had been inhibited. All samples from the wild boars were negative for Brachyspira spp., 12 of 48 samples were negative for L. intracellularis, and in 36 wild boar samples, the PCR was inhibited.
The aim of this study was to find suitable and reliable tools for demonstrating Lawsonia intracellularis in routine clinical diagnosis. Firstly, a method to prepare tissue samples before a polymerase chain reaction (PCR) was evaluated in pigs submitted for necropsy. Secondly, seven different faecal preparation methods and four different DNA polymerases were tested in single or nested PCR, with co-amplification of a mimic molecule. Thirdly, in selected pigs submitted for necropsy, tissue and faecal samples were examined histopathologically and by PCR, and blood samples were analysed serologically. Detection of L. intracellularis in tissue preparations by PCR showed good specificity and correlated to lesions found at necropsy. The sensitivity in spiked tissue samples was 10(1)-10(2) mimic molecules per tube. In faecal samples, nested PCR on boiled lysate gave the best result with a sensitivity of 10(2)-10(3) mimic molecules per reaction tube. However, because of the time-consuming procedure and the increased risk for contamination, a commercially available kit was preferred for routine diagnoses, despite a somewhat lower detection rate in subclinically infected pigs. In a few cases, the serological results differed from those obtained by PCR and by necropsy but the reason for this is not clear. This study indicates that the best method for diagnosis of acute enteritis in growers is PCR on faecal or tissue samples. To determine the presence of the bacteria in a herd, serology or repeated faecal sampling for PCR from target animals, or both, should be used.
Diarrhoea among growing pigs (8-13 weeks old) is a significant problem in many herds. Nine herds with poor performance and diarrhoea among growing pigs were selected on the basis of their piglet mean age at a body weight of 25 kg, compared to the overall mean age in Swedish herds. In addition, four herds with good average performance and no problems with diarrhoea were selected. Pigs were necropsied and samples for histology and microbiology were collected. Based on the necropsy findings, the pigs from the good performing herds were all judged to be healthy. The presence of Brachyspira pilosicoli and Lawsonia intracellularis was significantly correlated to poor performing herds and the results indicate that these microbes are main pathogens involved in enteric diseases among Swedish grower pigs. In addition, concomitant infections with other presumptive pathogens were commonly found.
BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. RESULTS: There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. CONCLUSION: Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.
The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.
Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), amylin and calcitonin (CT) are structurally and functionally related neuropeptides. It has recently been shown that the molecular pharmacology of CGRP and ADM is determined by coexpression of one of three receptor activity-modifying proteins (RAMPs) with calcitonin receptor-like receptor (CRLR). Furthermore, RAMP proteins have also been shown to govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. In this study, we have cloned the rat RAMP family and characterized the pharmacology of rat CGRP and ADM receptors. Rat RAMP1, RAMP2 and RAMP3 shared 72%, 69% and 85% homology with their respective human homologues. As expected CRLR-RAMP1 coexpression conferred sensitivity to CGRP, whilst association of RAMP2 or RAMP3 with CRLR conferred high affinity ADM binding. Using specific oligonucleotides we have determined the expression of RAMP1, RAMP2 and RAMP3 mRNAs in the rat central nervous system by in situ hybridization. The localization of RAMP mRNAs was heterogeneous. RAMP1 mRNA was predominantly expressed in cortex, caudate putamen and olfactory tubercles; RAMP2 mRNA was most abundant in hypothalamus; and RAMP3 was restrictively expressed in thalamic nuclei. Interestingly, in specific brain areas only a single RAMP mRNA was often detected, suggesting mutual exclusivity in expression. These data allow predictions to be made of where each RAMP protein may heterodimerize with its partner G-protein-coupled receptor(s) at the cellular level and consequently advance current understanding of cellular sites of action of CGRP, ADM, amylin and CT. Furthermore, these localization data suggest that the RAMP family may associate and modify the behaviour of other, as yet unidentified neurotransmitter receptors.
Several studies have reported asymmetric cognitive profiles in patients with Alzheimer's disease (AD), but these results have almost exclusively been found using non-memory cognitive instruments. The present study investigated whether AD patients who display lateralized profiles on non-memory cognitive instruments also exhibit asymmetric deficits on verbal versus spatial memory tests. Sixty-eight AD patients participated in the study: 36 with a "High Verbal" cognitive profile, and 32 with a "High Spatial" profile. The results indicated that the High Verbal AD patients performed significantly better than the High Spatial AD patients on verbal memory tests, but the two subgroups failed to differ on spatial memory tests. Implications of these findings for understanding the heterogeneous nature of cognitive profiles in AD patients are discussed.
The objective of this study was to determine whether endogenous nitric oxide (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or amplifies lung injury in mice breathing at a high oxygen tension. Previous studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced lung injury, and that endogenous NO derived from iNOS inhibits leukocyte recruitment and protects against lung injury induced by lipopolysaccharide. In the present study, hyperoxia (> 98% O(2) for 72 h) induced acute lung injury in both wild-type and iNOS-deficient mice as determined by elevated albumin and lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by increased extravascular lung water. Lung injury was greater in iNOS-deficient mice than in wild-type mice and was associated with an increased number of polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of reactive NO species, was expressed in both wild-type and iNOS-deficient mice in hyperoxia, indicating an iNOS-independent pathway for protein nitration. We conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and lung injury. The data indicate that iNOS induction serves as a protective mechanism to minimize the effects of acute exposure to hyperoxia.
PURPOSE: To develop a pig model that would enable repeated biopsy specimen collection and endoscopic monitoring of the gut. This would increase precision of the experiment and reduce the number of experimental animals required. METHODS: Six 10-week-old Yorkshire pigs underwent surgery, and a cannula was inserted in the cecum. Two pigs served as non-operated controls. The health status of the animals was monitored by clinical, hematologic, and biochemical examinations and by studies of gut motility and microbial flora. The experimental period lasted for eight weeks and approximately 45 biopsy specimens were obtained from each animal. RESULTS: Repeated endoscopy was performed and biopsy specimens were taken. Adverse effects on the animal's health were not apparent, and differences were not evident in transit time of digesta or in diversity of the gut microbial flora. After surgery there was a transient increase in the concentrations of haptoglobin, serum amyloid A, and plasma cortisol, and in body temperature and white blood cell count. CONCLUSIONS: It is possible to use an intestinal cannula in the cecum both for endoscopy and biopsy specimen collection. The procedures did not influence health status of the pigs, nor alter gut function. The method will be useful in experimental infection studies as well as in other physiologic investigations.
delta-catenin is a member of the Armadillo repeat family and component of the adherens junction discovered in a two-hybrid assay as a bona fide interactor with presenilin-1 (Zhou et al., [1997], NeuroReport 8:2085-2090), a protein which carries mutations that cause familial Alzheimer's disease. The expression pattern of delta-catenin was mapped between embryonic day 10 (E10) and adulthood by Northern blots, in situ hybridization and immunohistochemistry in the mouse. In development, delta-catenin is dynamically regulated with respect to its site of expression. It is first expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the mouse, delta-catenin mRNA is expressed by E10, increases and peaks at postnatal day (P)7, with lower levels in adulthood. In the developing neocortex, delta-catenin mRNA is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, delta-catenin protein forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By E18, delta-catenin expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood. The dynamic relocalization of delta-catenin expression during development, taken together with previously published data which described a role for delta-catenin in cell motility (Lu et al., [1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that delta-catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil.
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The present study further analyzes the growth and reorganization of the vessels adjacent to capillaries in the hyperoxia-adapted lung in response to a lower ambient oxygen tension. The aim of the study was to determine the source of the new smooth muscle cells known to develop in these segments on return to breathing air. To accomplish this we determined the reorganization of vessel walls by quantitative light-microscopy techniques, and vascular cell phenotype(s) by high-resolution microscopy, in the lungs of rats that breathed a high oxygen tension (87% O2 for 4 weeks), followed by weaning to a lower oxygen tension (87-20% O2 over 1 week) and return to breathing air (for 1, 2 or 4 weeks). Return to breathing air initially triggered wall growth in a subset of vessels and wall thinning in others before wall thinning predominated throughout the vessel population. Interstitial fibroblasts were identified as the source of new perivascular cells. The recruitment of these cells was accompanied by loss of elastic laminae from vessel walls. Subsequently, most perivascular cells expressed a smooth muscle phenotype and elastic laminae were restored. Arteriography demonstrated an increase in the number of patent vessels on return to air, and light- and high-resolution microscopy restitution of the capillary network. We propose that in the hyperoxia-adapted lung return to breathing air represents a relative hypoxia that triggers differential patterns of vessel and capillary growth to meet new functional demands set by the lower ambient oxygen tension.