Altered response to adaptive signals in transplanted intestine.
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Adaptation, Physiological↗
Biomedical subjects
D C Ferguson
Publications and source records attributed to D C Ferguson.
Does pheromone biology of Lambdina athasaria and L. pellucidaria contribute to their reproductive isolation?
Recently, 7-methylheptadecane and 7,11-dimethylheptadecane have been reported as sex pheromone components of both spring hemlock looper (SHL), Lambdina athasaria, and pitch pine looper (PPL), Lambdina pellucidaria. Our objective was to test the hypothesis that SHL and PPL are reproductively isolated, in part, through species specificity in: (1) absolute configuration of pheromone components, (2) diel periodicity of pheromonal communication, and/or (3) seasonal flight period. In coupled gas chromatographic-electroantennographic detection (GC-EAD) analyses of stereoselectively synthesized (7S)- and (7R)-7-methylheptadecane [7S; 7R] as well as (7S,11S)-, (7R,11R)-, and (meso-7,11)-7,11-dimethylheptadecane [7S,11S; 7R,11R; meso-7,11], only 7S and meso-7,11 elicited responses by male SHL and PPL antennae. In field experiments, male SHL and PPL were attracted only to lures containing 7S plus meso-7,11. In hourly recordings of trap-captured males, SHL and PPL in their respective habitats were trapped between 24:00 and 03:00 hr. Capture of both SHL and PPL in pheromone-baited traps throughout June indicated overlapping seasonal flight periods. These findings of identical absolute configuration of pheromoal components, diel periodicity of pheromonal communication, and overlap of seasonal flight periods support synonymy of SHL and PPL. Finite taxonomic classification of PPL and SHL must await careful assessment of further criteria, such as morphometrics, molecular comparisons and ecological analyses.
Animals↗
Structural adaptation in intestinal transplants.
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Animals↗
Canine thyrotropin beta-subunit gene: cloning and expression in Escherichia coli, generation of monoclonal antibodies, and transient expression in the Chinese hamster ovary cells.
The gene encoding the mature beta subunit of canine thyroid stimulating hormone (cTSH beta) was cloned, sequenced and expressed in Escherichia coli and in Chinese hamster ovary (CHO) cells, and monoclonal antibodies against the recombinant cTSH beta purified from E. coli were generated. The gene fragment that encodes mature TSH beta was cloned from the canine genomic DNA by direct polymerase chain reaction (PCR) using primers that were designed based on the consensus sequences from other species. The resulting 891 basepairs (bp) of genomic DNA consisted of two coding exons of the canine TSH beta gene and an intron of 450 bp. The two exons, which encode the mature cTSH beta subunit, was joined together by an overlap PCR and was expressed in E. coli as 6xHis-tagged protein. The purified recombinant cTSH beta with a molecular weight of about 15 kDa was recognized by the polyclonal antibodies prepared against the native canine TSH in Western blot. Monoclonal antibodies were raised against the purified cTSH beta and subsequently characterized. For transient expression in CHO cells that are permanently transfected with the bovine common alpha gene, a 60-oligonucleotide signal peptide coding sequence was added to the 5' end of the cTSH beta gene before it was cloned into the mammalian expression vector pRSV and used to transfect CHO cells. The medium from these transfected cells, presumably containing the bovine alpha and canine TSH beta in heterodimeric confirmation, exhibited TSH bioactivity as indicated by the stimulation of cAMP production in the cultured FRTL-5 thyrocytes.
Amino Acid Sequence↗
cDNA cloning of canine common alpha gene and its co-expression with canine thyrotropin beta gene in baculovirus expression system.
The common alpha gene of the canine glycoprotein hormones was cloned, sequenced and co-expressed with the canine thyrotropin beta (TSH beta) gene in the baculovirus expression system, and a bioactive recombinant canine TSH was purified. The canine common alpha gene was cloned from the total RNA extracted from the canine pituitary gland by the reverse transcription polymerase chain reaction (RT-PCR) using primers that were designed based on the consensus sequences from other species. The resulting 476 bp PCR product is consisted of the full coding sequence for the 96 amino acid mature alpha subunit, and a sequence encoding a 24 amino acid signal peptide. Homology analysis with other species revealed that the canine common alpha subunit potentially contains five disulfide bonds and two oligosaccharide chains N-linked to Asn residues located at positions 56 and 82. For expression in the baculovirus expression system, the common alpha gene was cloned downstream of the p10 promoter of the pAcUW51 transfer vector, and the previously cloned canine TSH beta gene was inserted under the polyhedrin promoter of the same vector. The recombinant virus containing both alpha and beta genes was generated and propagated before being used to transfect the Sf9 insect cells for expression. The medium from the Sf9 cultures, presumably containing canine TSH alpha and beta in native heterodimer confirmation, exhibited TSH bioactivity as indicated in the cAMP stimulation assay in FRTL-5 cells. The expressed recombinant protein was purified from the culture medium with an affinity column that was coupled with IgG purified from the polyclonal antibodies generated against the partially purified native canine TSH.
Amino Acid Sequence↗
Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats.
OBJECTIVE: To determine pharmacokinetics of troglitazone in healthy cats after i.v. and oral administration of a single dose of the drug. ANIMALS: 5 healthy ovariohysterectomized adult cats. PROCEDURE: Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight i.v. and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography. RESULTS: Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 +/- 0.1 hours. Steady-state volume of distribution was 0.23 +/- 0.15 L/kg. After i.v. administration, clearance was 0.33 +/- 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%. CONCLUSIONS AND CLINICAL RELEVANCE: The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans.
Administration, Oral↗
Comparison of ileal and jejunal transplantation after 50% proximal intestinal resection.
BACKGROUND: The ileum has a greater adaptive capacity than the jejunum after intestinal resection. Transposition studies suggest that this is, in part, related to increased exposure to nutrients. However, there may be regional differences in intestinal properties that contribute to this response as well. The aim of this study was to compare the outcome of replacing the jejunum with either ileal or jejunal transplants while preserving an intact ileum after 50% proximal resection. METHODS: Twenty-one Lewis rats were included in the study. One group (n = 7) served as transection controls (TC). The other two groups (n = 7) had 50% proximal resection with syngeneic transplantation of a similar length of ileum (ITX) or jejunum (JTX). Nutritional status and adaptation were studied at 14 days. RESULTS: JTX animals gained less weight than TC and ITX (104 +/- 2% vs 114 +/- 1 and 108 +/- 2% initial, P < 0.05). ITX and JTX groups had lower caloric intake and serum albumin levels compared with TC (7.4 +/- 0.4 and 7.2 +/- 0.8% vs 8.8 +/- 0.2% body weight and 2.6 +/- 0.1 and 2.4 +/- 0.9 g/dl vs 3.0 +/- 0.1 g/dl, P < 0.05). Mucosal thickness increased significantly in the ileal remnant of both ITX and JTX groups (9.2 +/- 2.1 and 8.8 +/- 0.6 micrometer vs 6.6 +/- 0.6 micrometer, P < 0.05). Transplanted ileum had mucosal thickness similar to that of jejunum. CONCLUSIONS: Transplanted ileum achieves an intestinal structure similar to that of the jejunum in the same environment. Modest adaptation of the remnant occurs with transplantation. Replacing jejunum with ileum rather than jejunum resulted in better weight gain, suggesting that intrinsic absorptive, motor, or hormonal rather than structural differences are responsible.
Animals↗
Diagnostic utility of glycosylated hemoglobin concentrations in the cat.
Changes in glycosylated hemoglobin (GHb) concentrations, K values (% disappearance of glucose/min after an intravenous injection of 1 g/kg dextrose), and blood glucose concentrations were examined in eight cats before and during the induction of diabetes, and in four of these cats after they were placed on insulin treatment. There was a statistically significant separation of GHb, K values, and fasting blood glucose concentrations between healthy and diabetic cats. Changes in GHb correlated best with the K value and single weekly fasting glucose concentrations averaged over eight periods for each cat while diabetes was induced (R = 0.80 and 0.78, respectively); however, fasting blood glucose concentrations obtained on the day of the GHb measurement were also highly correlated (R = 0.69; P < 0.001). The correlation between GHb and single weekly glucose concentrations obtained in insulin-treated cats at the time of insulin peak action and averaged over an 8-wk time period for each cat was less but still significant (R = 0.53; P < 0.001). It is concluded that GHb measurements are a simple and reliable way to monitor changes in glucose control in the diabetic cat over a prolonged period.
Animals↗
Pharmacokinetics of the antihyperglycemic agent metformin in cats.
OBJECTIVE: To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug. ANIMALS: 6 healthy adult ovariohysterectomized cats. PROCEDURE: In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography. RESULTS: Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean +/- SD) 11.5+/-4.2 hours. Metformin was distributed to a small central compartment of 0.057+/-0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12+/-0.02 and 0.37+/-0.38 L/kg. Steady-state volume of distribution was 0.55+/-0.38 L/kg. After IV administration, 84+/-14% of the dose was excreted unchanged in urine, with renal clearance of 0.13+/-0.03 L/h/kg; nonrenal clearance was negligible (0.02+/-0.02 L/kg). Mean bioavailability of orally administered metformin was 48%. CONCLUSIONS: The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction. CLINICAL RELEVANCE: On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans.
Administration, Oral↗
Synchronous intestinal transplantation inhibits post resection adaptation.
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Anastomosis, Surgical↗
Structure-based design of a constrained peptide mimic of the HIV-1 V3 loop neutralization site.
Antigenic variation among different HIV-1 isolates has been a major problem in the development of an effective vaccine against AIDS. Peptide vaccines incorporating structural elements common to groups of viral isolates, such as the clade subtypes of HIV-1, hold promise; however, the design of such immunogens has been hampered by the lack of specific structural information on the viral proteins to be targeted. As part of a structure-based approach to this problem, we report the design and characterization of a conformationally restricted peptide analog (Aib142) of a highly conserved HIV-1 clade-B sequence from the third variable loop of the membrane glycoprotein gp120. The design strategy incorporates peptide conformational data derived from crystal structure analysis of an MN-isolate peptide (RP142) in complex with the Fab fragment (Fab59.1) of a broadly neutralizing antibody. The synthetic peptide (Aib142) replaces an alanine residue within the V3 loop epitope sequence GPGRAF by the conformationally restricted helicogenic alpha-aminoisobutyryl residue. As expected, the crystal structure of the Fab 59.1-Aib142 complex at 2.8 A resolution shows that the peptide interacts very similarly with the neutralizing antibody. Proton nuclear magnetic resonance (NMR) studies indicate that the free Aib142 peptide is indeed more ordered in solution with a conformational preference that corresponds to the X-ray structure of its Fab-bound form. Aib142 thus represents the first step in the design of conformationally constrained peptide analogs built to mimic biologically relevant structural forms of HIV-1 neutralization sites.
AIDS Vaccines↗
Effects of parathyroidectomy on induced renal failure in dogs.
OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery). PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for a 24-month period of study and monitored for clinical, hematologic, blood biochemical, and organ function status. On development of uremia or after 24 months, dogs were euthanatized, and tissues were examined. RESULTS: Higher survival rate and smaller decrement in renal function (glomerular filtration rate) were observed in PTX dogs, compared with those that had sham surgery, but values did not reach statistical significance. The PTX dogs remained hypocalcemic during the study and had lower serum Ca2+ X P product values. Regardless of parathyroid state, survivors and fatalities could be separated on the basis of serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition of calcium, and renal lesions were poorly correlated with renal cortical calcium concentration. Abnormalities reported in dogs with renal failure, which were attributed to PTH (glucose intolerance, pulmonary hypertension), were not observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL RELEVANCE: PTX had beneficial effects, but these were mediated via changes in mineral homeostasis rather than via direct effects of PTH. Results attributable to PTX were similar to those previously obtained by dietary restriction of phosphate intake.
Acidosis↗
On-line veterinary communities: the time is now or I've got a modem: what should I do with it? Where should I point it?
Veterinary medicine has until recently existed as a small and geographically diffuse group of professionals. Communicating with significant numbers of colleagues to confer on cases or business related issues on a regular basis has been limited primarily to those in academia. Isolation has prevented the individual practice from significantly affecting the policies of national suppliers or the politics of organized veterinary medicine through a large unified voice. Although only a small percentage of the profession is on-line, the building of on-line communities of veterinarians is currently changing the rules in these areas. Considering when, why, and how to venture into the world of on-line veterinary medicine is only part of the issue we face as a profession. Choosing to keep a sense of community as the centerpiece of on-line veterinary interactions is critical to ensuring that on-line veterinary medicine, above all, serves the best interests of the practicing veterinarian.
Humans↗
Relationship between plasma creatinine concentration and glomerular filtration rate in dogs.
Glomerula filtration rate (GFR), plasma creatinine concentration (CR), and plasma urea nitrogen concentration (BUN) were measured in 129 adult dogs with reduced renal mass. A preliminary examination of the relationship between CR and GFR was conducted, and the inverse model (GFR vs. 1/CR) was chosen for further evaluation. The slope of the regression of GFR on 1/CR which was computed from actual data was not statistically different from a theoretical regression line generated from the clearance equation. Evaluation of subsets of the population revealed no significant difference between male (n = 69) and female (n = 60) dogs on the slope of the regression equations. Diets differing in protein concentration (16% protein, n = 35: 21% protein, n = 75: 32% protein, n = 19) did not cause a significant difference in the slope of the regression equations. The regression equation and the confidence intervals generated in this study may be used to predict a probable range of GFR values from CR in individual dogs. Such values may be useful in adjusting drug dosages in dogs with renal disease. However, since the derived equation did not differ significantly from the theoretical inverse relationship between GFR and CR, it remains to be established whether the equation is advantageous.
Animals↗
Thyroid hormone metabolism. A comparative evaluation.
Knowledge of thyroid hormone and iodide metabolism is derived from a combination of in vivo and in vitro studies in a variety of mammalian species including cats, dogs, and humans. Each species provides a unique opportunity to investigate various aspects of normal or altered thyroid hormone physiology. Availability of sensitive and specific human TSH assays has allowed detailed studies of the human hypothalamic-pituitary-thyroid axis which have not been possible in cats and dogs to date. Similarities and differences of thyroid hormone metabolism in dogs, cats, and humans provide the basis for a better understanding of normal physiology as well as shedding light on the significance of changes induced by spontaneous or induced thyroidal and nonthyroidal disorders.
Animals↗
Update on diagnosis of canine hypothyroidism.
Until a clinically useful canine TSH assay is available, a valid test of thyroid hypofunction should (1) take into consideration valid (or at least predictive) measurement of the free T4 concentration in order to factor out the binding effects of drugs and nonthyroidal illness, and (2) should assess thyroid functional reserve. A validated equilibrium dialysis measurement of free T4 and the TSH stimulation test, provide the most useful diagnostic combination of tests now available. A therapeutic trial with L-thyroxine, despite being relatively safe, should be reserved once other diagnoses have been ruled out, and should be reevaluated to assure a clinical response which can be attributable to the medication.
Animals↗
Etiopathology of feline toxic nodular goiter.
We have discussed the etiopathology of feline toxic nodular goiter in the context of human nodular goiter pathogenesis. We have reviewed thyroid heterogeneity, growth regulation, functional and growth autonomy, nodule and tumor formation, and the evolution of toxic nodular goiter in the human being. By addressing toxic nodular goiter of the cat, the history, morphologic findings, xenotransplantation and cell culture studies, evidence for and against circulating thyroid stimulators and epizootiological studies of the feline disease have been summarized. Due to its structure, the thyroid gland offers some unique possibilities to study the mechanisms that are responsible for cellular heterogeneity, the emergence of autonomous nodular growth and function, and, ultimately, the development of tumors. The demonstration of naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of the thyroid has fostered promising new concepts on the genesis of nodular growth of benign and possibly malignant endocrine tumors. Hyperthyroid cat goiters contain single or multiple, autonomously (i.e., TSH-independently) functioning and growing nodules. Neither hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells. The factors enhancing the transformation of a normal thyroid into a nodular hyperfunctioning goiter over many years are still unknown. Immunological, environmental, and nutritional factors are the focus of ongoing studies, but an infectious agent can not yet be excluded.
Animals↗
Experimental use of high-frequency ultrasound to image bowel wall after porcine intestinal transplantation.
A means to monitor intestinal allografts will be crucial for the future success of small bowel transplantation. We have previously demonstrated the ability of high-frequency ultrasound (US) to diagnose porcine intestinal ischemia in vitro. The aim of this study was to compare the histologic appearance of normal porcine small bowel versus bowel undergoing acute rejection, using 8.5-MHz US images. We allowed porcine heterotopic small bowel allograft transplants to reject and then removed, at scheduled intervals from postoperative day 0 to 12, specimens of both the transplanted bowel and the native bowel. We examined the tissues in vitro with an 8.5-MHz linear array US system then studied them histologically. Histologically, the earliest changes of rejection occurred at days 4 to 5, with mild submucosal edema, endotheliitis, and vasculitis affecting the small vessels; the mucosa remained normal. By days 7 to 8, the submucosal endotheliitis became more prominent, with focal thrombosed small vessels; the mucosa now appeared abnormal with flattened villi, erosions, and necrosis. By days 10 to 12, marked submucosal edema, vasculitis, endotheliitis, and necrotic mucosa were present. Ultrasonically, normal intestinal wall has five wall layers, corresponding to mucosa, submucosa, muscularis propria, and subserosal fat. The US criteria for abnormality were loss of folds, decreased numbers of echo layers, discontinuity of layers, and a homogeneous appearance. Using these US criteria, blinded observers differentiated normal from abnormal bowel wall after transplantation with a sensitivity of 84% and a specificity of 81%. Most of the errors occurred with the day 4 and 5 specimens, which appeared nearly normal on US.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗