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R J Kemppainen

Publications and source records attributed to R J Kemppainen.

At least 19 recordsLinked to original sources
PubMed2004

Increased expression of MAIL, a cytokine-associated nuclear protein, in the prodromal stage of black walnut-induced laminitis.

REASONS FOR PERFORMING STUDY: The mediators and signalling cascades important in the initiation of laminitis remain unclear. We therefore wanted to explore the genes and overall signalling mechanisms that play an important role in the developmental stage of laminitis. OBJECTIVE: To use a broad genomic screening technique to identify novel genes that are differentially regulated in the equine lamellae during the developmental period of laminitis. METHODS: Differential mRNA display (DRD) was performed to discover regulated genes, and real-time quantitative polymerase chain reaction (RT-qPCR) was then used to evaluate lamellar mRNA levels of a regulated gene (MAIL) and mediators related to that gene (IL-1beta and IL-6) in control horses (n = 5) and horses administered black walnut extract (BWE; n = 5). RESULTS: Using DRD, MAIL was identified as a regulated gene. RT-qPCR indicated a 4-fold increase in expression of the MAIL mRNA in BWE lamellae compared to controls. A 30-fold increase in IL-1beta, and a 160-fold difference in IL-6 mRNA expression was present in BWE lamellae. Differences in MAIL, IL-1beta and IL-6 mRNA expression were statistically significant between groups (P < 0.05). CONCLUSIONS AND POTENTIAL RELEVANCE: The data strongly support a role for inflammatory cytokines in the developmental stages of laminitis, possibly inducing the vascular and metabolic alterations reported to occur in the affected digit. These results potentially support the use of anti-inflammatory drugs in horses at risk of laminitis, and warrant further investigation of the link between systemic disease processes associated with laminitis and the reported digital inflammation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Diagnosis of canine hypothyroidism. Perspectives from a testing laboratory.

The most common sample received by our endocrine testing laboratory is submitted for the diagnosis of hypothyroidism in a dog. The current tests most frequently employed in our laboratory for thyroid evaluation in dogs are total T4, free T4 by dialysis, and canine TSH measurement. Each test has strengths and weaknesses and suffers from the possibility of both false positive and false negative results. This article provides a working description of each test and an approach to interpretation of results. Other tests that are less commonly used are also discussed. Examples of interpretation of test results in individual hypothyroid-suspect dogs are presented for illustration.

Animals↗
PubMed2001

Diagnosis of canine hyperadrenocorticism.

Canine hyperadrenocorticism is one of the most common endocrinopathies in dogs. Diagnosis remains difficult in some cases due to factors such as the presence of non-adrenal illness and limitations in the tests. Differentiation between the pituitary and adrenal forms is important for providing accurate prognostic information and delineating treatment options and protocols. This article reviews the tests available for diagnosis (screening) and differentiation and evaluates their advantages and disadvantages. Recommendations for testing are made.

Abdomen↗
PubMed2001

Regulation of Dexras1 expression by endogenous steroids.

Dexras1, a newly identified member of the Ras superfamily of proteins, was discovered in AtT-20 corticotrope cells because its expression was induced in response to glucocorticoids (dexamethasone; Dex). As yet, the function of Dexras1 is unknown, but its rapid induction in response to glucocorticoids suggests the possibility that it may be involved in negative feedback regulation of corticotropin secretion. To better understand the control of Dexras1 expression, possible effects of other steroid hormones on its expression were studied in both AtT-20 cells and in mouse pituitaries. AtT-20 cells were treated with each of 6 steroids [aldosterone, corticosterone (Cort), Dex, beta-estradiol (E(2)), progesterone and testosterone] for 2 h. Dexras1 expression was assessed using both reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis. Expression of the gene was only induced in response to glucocorticoid treatment (Dex or Cort). The 6 steroids were also injected into mice, pituitaries were harvested and total RNA was obtained for RT-PCR analysis. Surprisingly, treatment with E(2), not only injection of glucocorticoids, induced Dexras1 expression in mouse pituitary. Other steroids were without effect. The results suggest that in AtT-20 corticotropes, Dexras1 expression is only induced by glucocorticoid-type steroids. In pituitary glands of mice, the gene's expression is also responsive to E(2). We conclude that either Dexras1 expression in corticotropes from normal mice is regulated differently from that in AtT-20 cells, or that Dexras1 is also expressed in other pituitary cells than corticotropes.

Animals↗
PubMed2000

Reduced growth of calves and its reversal by use of anabolic agents.

Disease has profound effects on the immune system, endocrine system, and on the growth process. Since diseases are catabolic to the animal, there is current interest in the possible role of anabolic hormones to counter the effects of disease in general and minimize the effects of a disease process on growth and development. A number of anabolic hormones, such as growth hormone (GH) and estradiol + progesterone (EP), have been studied for their role in enhancing growth and stimulating immune function and are thus candidates for hormonal intervention in disease processes. GH has been shown to be effective in countering some of the deleterious effects of endotoxemia but was ineffective in a parasitic disease model. Studies with EP have shown similar success with both endotoxemia and a parasitic disease model. Moreover, GH and EP do not share a common mechanism of action, suggesting that the effects are not simply due to anabolic actions. While the mechanism of action of GH in endotoxemia has been examined, the effects of EP are via an unknown mechanism, possibly by inhibition of IL-I action or inhibition of nitric oxide overproduction.

Animals↗
PubMed1999

Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.

Adrenal Cortex Function Tests↗
PubMed1999

Regulation of alpha-melanocyte-stimulating hormone secretion from the pars intermedia of domestic cats.

OBJECTIVE: To identify factors regulating secretion of alpha-melanocyte-stimulating hormone (alpha-MSH) from the pars intermedia (PI) of the pituitary gland of cats. ANIMALS: 28 healthy adult cats. PROCEDURE: Indwelling catheters were placed in 1 jugular vein of each of 7 to 10 cats, depending on treatment group. Sixteen hours later, 3 blood samples were collected for determination of baseline plasma hormone concentrations, and saline solution or a test substance (haloperidol, corticotropin-releasing hormone, bromocriptine, isoproterenol, insulin, or dexamethasone) was administered via the catheter. Subsequent blood samples were collected at regular intervals for up to 240 minutes after injection. Concentrations of ACTH, cortisol, and alpha-MSH were measured in plasma by use of specific radioimmunoassays. Cats were rested for at least 3 weeks between experiments. RESULTS: Administration of haloperidol and isoproterenol resulted in increased, and bromocriptine and insulin in decreased, circulating concentrations of alpha-MSH from baseline. ACTH and plasma cortisol concentrations increased after administration of all test substances except dexamethasone. Dexamethasone injection resulted in decreased plasma concentrations of ACTH and cortisol. CONCLUSIONS: Secretion of alpha-MSH from the PI of cats appears to be inhibited by dopaminergic activity and stimulated by beta-adrenergic influences. Activation of secretion of alpha-MSH from the PI can be dissociated from activation of secretion of other pro-opiomelanocortin-derived peptides, such as ACTH, arising from the pars distalis. Regulation of secretory activity of the PI of cats resembles that of rats.

Adrenergic beta-Agonists↗
PubMed1999

Effect of alternate-day prednisolone administration on hypophyseal-adrenocortical activity in dogs.

OBJECTIVE: To evaluate effect of alternate-day oral administration of prednisolone on endogenous plasma ACTH concentration and adrenocortical response to exogenous ACTH in dogs. ANIMALS: 12 Beagles. PROCEDURE: Dogs were allotted to 2 groups (group 1, 8 dogs treated with 1 mg of prednisolone/kg of body weight; group 2, 4 dogs given excipient only). During a 30-day period, blood samples were collected for determination of plasma ACTH and cortisol concentrations before, during, and after treatment with prednisolone. From day 7 to 23, prednisolone or excipient was given on alternate days. Sample collection (48-hour period with 6-hour intervals) was performed on days 1, 7, 15, 21, and 28; on other days, sample collection was performed at 24-hour intervals. Pre- and post-ACTH plasma cortisol concentrations were determined on days 3, 9, 17, 23, and 30. RESULTS: A significant difference was detected between treatment and time for group 1. Plasma ACTH concentrations significantly decreased for 18 to 24 hours after prednisolone treatment in group-1 dogs. At 24 to 48 hours, ACTH concentrations were numerically higher but not significantly different in group-1 dogs. Post-ACTH plasma cortisol concentration significantly decreased after 1 dose of prednisolone and became more profound during the treatment period. However, post-ACTH cortisol concentration returned to the reference range 1 week after prednisolone administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Single oral administration of 1 mg of prednisolone/kg significantly suppressed plasma ACTH concentration in dogs for 18 to 24 hours after treatment. Alternate-day treatment did not prevent suppression, as documented by the response to ACTH.

Adrenal Cortex↗
PubMed1998

Effect of storage conditions on cortisol, total thyroxine, and free thyroxine concentrations in serum and plasma of dogs.

OBJECTIVE: To determine for dogs stability of cortisol, thyroxine (T4), and free thyroxine (fT4) in plasma and serum stored in glass or plastic tubes at -20, 4, 25, and 37 C. DESIGN: Prospective study. ANIMALS: Phase I, 7 Greyhounds; Phase II, 6 mixed-breed dogs. PROCEDURE: Phase I: blood was obtained after administration of thyroid-stimulating hormone and adrenocorticotropin. Serum and plasma samples from each dog were divided into 8 aliquots, 4 in glass and 4 in plastic tubes. A pair of aliquots, 1 in plastic and 1 in glass, were stored at -20, 4, 25, or 37 C for 5 days and then assayed for hormones. Phase II: blood was obtained without prior stimulation. For fT4 determination, serum from each dog was placed in plastic or glass tubes, assayed immediately, stored at -20 C for 5 days, and reassayed. Aliquots from each dog were also stored for 1 day at 4 or 25 C and then assayed. Samples for cortisol determination were handled as in phase I. RESULTS: Phase I: there was no effect of tube type (glass vs plastic) on cortisol. Cortisol concentrations decreased after storage in serum at 4, 25, and 37 C, and in plasma at 37 C, compared with storage at -20 C. There was no effect of sample type (serum or plasma) on T4. Thyroxine concentrations increased after storage at 37 C in glass, compared with storage at -20 C. The fT4 concentrations were lower in serum than plasma after storage at -20 C. Concentrations of fT4 increased after storage at 37 C in glass, compared with storage at -20 C. Phase II: the fT4 concentrations did not change after storage in any condition. There was no effect of tube type on cortisol concentrations. Serum cortisol concentrations decreased after storage at 37 C, compared with storage at -20 C. CLINICAL IMPLICATIONS: For cortisol, cooling of plasma is not necessary, but serum should be shipped cold. For T4 and fT4, serum is sufficient; contained within plastic tubes, samples can be shipped without cooling if assayed within 5 days.

Analysis of Variance↗
PubMed1998

Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells.

Differential display was used to identify a new Ras superfamily gene (Dexras1) induced by dexamethasone (Dex) in AtT-20 cells. Treatment of AtT-20 cells with Dex for 30 min resulted in increased mRNA for Dexras1; the highest concentrations appeared after 2 h of treatment. The gene was also identified in mouse heart, brain, liver, and kidney and furthermore was induced in these tissues after Dex treatment. The deduced protein shows regions of homology characteristic of members of the Ras superfamily of small GTPases. Highest homology (36% identity, 57% positives) was found with human Rap-2b, followed closely by a number of other Ras subfamily members, suggesting that Dexras1 is probably a member of the Ras subfamily of GTPases (members include Ras and Rap). Dexras1 is the first Ras superfamily member identified that is induced in response to steroids. The function of this gene is unknown; however, its wide distribution and rapid induction by Dex suggests the possibility of a role in glucocorticoid action in a variety of tissues.

Amino Acid Sequence↗
PubMed1998

Enhancement of secretagogue-induced adrenocorticotropic hormone release from cultured sheep anterior pituitary cells by recombinant ovine interleukin 1.

OBJECTIVE: To determine whether recombinant ovine interleukin (oIL)-1 or oIL-2 alters basal or hypothalamic peptide-induced secretion of ACTH from cultured sheep pituitary cells. ANIMALS: The pituitary gland was collected from castrated male sheep ranging from 0.5 to 1 year old. PROCEDURE: Cells were cultured for 3 to 5 days, then were treated with oIL for variable periods. Cells were washed and treated with the hypothalamic peptides corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) or both. Medium bathing the cells was collected and assayed for ACTH concentration. RESULTS: Ovine IL-1 alpha and oIL-1 beta, but not oIL-2, increased the amount of ACTH released in response to CRH, AVP, and CRH and AVP combined. Both oIL were effective after 3, but not 18 or 24 hours of exposure. Treatment with oIL-1 did not affect basal release of ACTH. Exposure of cells to phorbol 12-myristate 13-acetate or calphostin C before treatment with oIL-1 beta inhibited the ability of the cytokine to augment ACTH release, suggesting a role for protein kinase C in the process. CONCLUSIONS: Local concentration of oIL-1 in the sheep pituitary gland may have an important role in determining secretion of ACTH in response to CRH or AVP or both from the hypothalamus. CLINICAL RELEVANCE: The hypothalamic-pituitary-adrenocortical axis may be activated after immune challenge. The cytokine oIL-1 has been implicated as an important mediator in this process. The pituitary gland may be an important target for this effect.

Adrenocorticotropic Hormone↗
PubMed1998

Effect of endotoxin on hormonal responses to thyrotropin and thyrotropin-releasing hormone in dogs.

OBJECTIVE: To determine whether administration of endotoxin affects thyroid gland function in dogs. ANIMALS: 24 Beagles. PROCEDURE: Dogs were given thyrotropin (TSH) or thyrotropin-releasing hormone (TRH) on 2 occasions. Twenty-four hours before the second challenge with TSH or TRH, all dogs were given 5 micrograms of endotoxin/kg of body weight. Serum concentrations of thyroxine (T4), free T4 (fT4), 3,3',5-triiodothyronine (T3), reverse T3, autoantibodies to T3, and plasma concentrations of ACTH and cortisol were determined. RESULTS: Treatment with endotoxin was associated with reduced baseline concentration of serum T3 and increased baseline concentration of reverse T3 and free T4. Endotoxin treatment resulted in reduced peak serum concentration of T4 after TSH and TRH. However, peak serum concentration of fT4 after TSH and TRH were not affected by endotoxin. CONCLUSIONS: A single dose of endotoxin affects several aspects of thyroid gland function in dogs, including T4 binding, deiodinase activity, and the thyroidal response to TSH and TRH. CLINICAL RELEVANCE: Acute or chronic nonthyroidal illness may affect thyroid gland function in dogs. Determination of fT4 concentration may provide a means of differentiating the effects of nonthyroidal illness from those of thyroid dysfunction, because endotoxin treatment was associated with increased baseline serum free T4 concentration and unchanged peak serum fT4 concentration after administration of TSH or TRH.

Adrenocorticotropic Hormone↗
PubMed1997

Adrenal physiology.

The adrenal glands contain elements of three distinct functional units: (1) the medulla, which secretes catecholamines; (2) the zona glomerulosa, which is responsible for mineralocorticoids (aldosterone); and (3) the zonae fasiculata and reticularis, which are the sources of glucocorticoids (cortisol). The medulla is a part of the sympathetic nervous system and releases epinephrine and norepinephrine in response to stressful stimuli. Aldosterone secretion is regulated mainly by changes in extracellular fluid-water volume and pressure, and sodium and potassium concentrations in blood. Through its actions in the kidney, aldosterone acts to retain sodium and water and enhance excretion of potassium. Glucocorticoid secretion is regulated by adrenocorticotropin from the pituitary. Cortisol has diverse actions on virtually all body tissues. One important effect of this steroid is to provide a negative feedback signal, inhibiting adrenocorticotropic hormone release.

Adrenal Cortex↗
PubMed1997

Glucocorticoid therapy. Pharmacology, indications, and complications.

Glucocorticoids are one of the most commonly prescribed classes of medication in veterinary medicine, with numerous applications ranging from physiologic replacement therapy to immunosuppression. Due to the presence of glucocorticoid receptors in almost all cells, both the desired and undesired effects of glucocorticoid therapy are manifold. This article discusses the physiologic alterations possible with glucocorticoid therapy, glucocorticoid pharmacology, nonendocrine indications, and different therapeutic strategies. The adverse reactions potentially associated with glucocorticoid therapy also are examined.

Animals↗
PubMed1996

Domestic cats show episodic variation in plasma concentrations of adrenocorticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), cortisol and thyroxine with circadian variation in plasma alpha-MSH concentrations.

Blood samples were collected from 31 healthy domestic cats to characterize possible episodic and/or circadian variation in plasma concentrations of adrenocorticotropin (ACTH), cortisol, thyroxine and alpha-melanocyte-stimulating hormone (alpha-MSH). Samples were collected with minimal disturbance through indwelling jugular cannulae at two frequencies: at 20-min intervals for 3 h for evaluation of episodic variation, and at 2-h intervals for 48 or 72 h to identify possible circadian changes. Episodic peaks in profiles of all hormones were found in the majority of cats. When data were compared across four bleed periods (each of 3 h duration), no differences were detected in average hormone concentrations or characteristics of episodic pulses. Correlation analyses showed a significant (p < 0.001) relationship between concentrations of ACTH and cortisol (r = 0.44) when these hormones were measured in the same plasma sample. A weaker but significant correlation (r = 0.13, p < 0.05) was also detected between concentrations of ACTH and alpha-MSH, suggesting that proopiomelanocortin peptide secretion from the pars distalis and pars intermedia occurs at least on occasion in synchrony. No differences in hormonal profiles were noted when comparing data across sexes. Data from the studies designed to evaluate circadian change (48 and 72-h bleed periods) indicated that, of the four hormones, only concentrations of alpha-MSH changed with a significant circadian periodicity. A significant circadian component of period length 24-25 h was detected in 37% (seven of 19) of cats examined. Concentrations of alpha-MSH were greatest coincident with or shortly after the onset of darkness. These findings indicate that pituitary-adrenocortical hormones are secreted episodically in domestic cats and that, in contrast to the patterns shown by ACTH and cortisol, secretion of the pars intermedia product alpha-MSH occurs with a circadian rhythm in about one-third of cats.

Adrenocorticotropic Hormone↗
PubMed1995

Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs.

The purpose of the study reported here was to assess 3 commonly used screening tests for hyperadrenocorticism (low-dose dexamethasone suppression test, ACTH stimulation test, and urinary cortisol:creatinine ratio) in dogs with various diseases other than those of the adrenal glands (nonadrenal diseases). A group of 100 dogs was studied: 59 dogs with nonadrenal disease, 21 clinically normal dogs, and 20 dogs with pituitary-dependent hyperadrenocorticism. Of 59 dogs with nonadrenal disease, 20 (34%) had high baseline cortisol concentration (greater than reference range limits), and 22 (38%) and 33 (56%) had inadequate serum cortisol suppression at 4 and 8 hours, respectively, after administration of a low dose of dexamethasone. Compared with clinically normal dogs, dogs with nonadrenal disease had significantly (P < 0.05) higher mean serum cortisol concentration at 4 and 8 hours after administration of a low dose of dexamethasone; however, significant differences were not detected between the mean cortisol concentration at 8 hours after administration for dogs with nonadrenal disease and for dogs with hyperadrenocorticism. After ACTH stimulation, only 8 of 59 (14%) dogs with nonadrenal disease had high serum cortisol concentrations. Significant differences did not exist after ACTH stimulation between mean cortisol concentration of clinically normal dogs and that of dogs with nonadrenal disease. Of 59 dogs with nonadrenal disease, 45 (76%) had a high urinary cortisol:creatinine ratio. When compared with clinically normal dogs, dogs with nonadrenal disease had a significantly higher mean urinary cortisol:creatinine ratio, but significant differences did not exist between the mean urinary cortisol:creatinine ratio of dogs with nonadrenal disease and that of dogs with hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocortical Hyperfunction↗
PubMed1995

Evidence for a single glucocorticoid regulated pool of adrenocorticotropin in sheep anterior pituitary.

The goal of this study was to determine whether separate glucocorticoid-sensitive releasable pools of adrenocorticotropic hormone (ACTH) could be distinguished in sheep anterior pituitary cells. Isolated cells were cultured in serum-free medium containing 0-10 nM cortisol (F) for 7-11 days to determine whether variation in the glucocorticoid environment selectively affected ACTH release stimulated by corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP). Secretion was studied using a microperifusion system. The results indicated that while the concentration of F in the medium bathing the cells profoundly influenced the magnitude of ACTH released in response to either peptide, the fractional release of total ACTH was unchanged. F concentration in culture medium similarly did not alter the negative-feedback effectiveness of a larger dose of F applied to cells 45 min before treatment with CRH or AVP. These results support the existence of a single glucocorticoid-sensitive pool of ACTH in corticotrophs.

Adrenocorticotropic Hormone↗