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Biomedical subjects

B A Jackson

Publications and source records attributed to B A Jackson.

At least 19 recordsLinked to original sources
PubMed1997

Stimulus-secretion coupling in porcine adrenal chromaffin cells: effect of dexamethasone.

Recent studies from this laboratory established that dexamethasone (DEX) potentiates Ca2+ current via voltage-gated Ca2+ channels (VGCC), and as a consequence potentiates agonist-induced cytosolic Ca2+ transients in rat adrenal chromaffin cells. The present study examined whether DEX can also modulate VGCC activity and agonist-induced cytosolic Ca2+ transients in porcine adrenal medullary chromaffin (PAMC) cells, and if so whether this results in alterations in catecholamine secretion. Forty-eight-hr exposure to 1 microM DEX significantly increased peak Ca2+ current (delta + 138%; n = 6; P < 0.05) in PAMC cells. DEX treatment also significantly potentiated the increase in cytosolic Ca2+ in response to membrane depolarization with KCl (delta + 20%; n = 29; P < 0.05), but did not affect the amplitude of Ca2+ transients elicited by nicotine or acetylcholine. Despite the potentiation of intracellular Ca2+, DEX treatment had no effect on KCl-induced secretion of either norepinephrine or epinephrine. These data demonstrate that as in the rat chromaffin cell, DEX can also increase VGCC activity in PAMC cells. However, the subsequent potentiation of selected agonist-induced increases in intracellular Ca2+ does not appear to be sufficient to alter catecholamine secretion.

Acetylcholine↗
PubMed1997

Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors.

Replacing the G-protein-coupling domains of the beta 2-adrenergic receptor with homologous domains of putative olfactory receptors produced chimeric receptors which were able to stimulate pigment dispersion in Xenopus melanophores, a G-protein-mediated pathway. A multiple replacement chimera containing the second, third and C-terminal cytoplasmic domains of receptor OR5 elevated cyclic adenosine 3':5'-monophosphate (cAMP) and suppressed production of inositol phosphates. Co-expression of G alpha olf did not alter the strength of response of this chimera. A novel rat olfactory receptor cDNA (U131) was isolated and sequenced. Expression of U131 and OR5 constructs containing an N-terminal epitope-tag or C-terminal fusion to green fluorescent protein occurred in an intracellular network but not in the plasma membrane of heterologous cells. Similarly treated beta 2-adrenergic receptors were functional and were observed in the plasma membrane and the intracellular network. These results demonstrate that the putative cytoplasmic domains of olfactory receptors are capable of functional interaction with heterologous G-proteins of the G alpha s subtype. Instead, the absence of these receptors from the plasma membrane of heterologous cells appears to explain our inability to determine if odorants can activate the olfactory receptor clones. We hypothesize that the olfactory receptors have requirements for maturation and targeting to the plasma membrane that are different from most other G-protein-coupled receptors.

Adenylyl Cyclases↗
PubMed1997

Effect of pectin on satiety in healthy US Army adults.

OBJECTIVE: We tested the hypothesis that pectin, a source of dietary fiber that delays gastric emptying, increases satiety. METHODS: Male (n = 49) and female (n = 25) US Army employees within normal weight limits were fasted overnight then fed 448 mL of orange juice on 2 separate days followed 4 hours later by 0.473 L of ice cream. On 1 of the 2 days, 5, 10, 15 or 20 g of pectin was mixed with the orange juice. Satiety was measured on a visual analog scale before and at 0, 1, 2, 3 and 4 hours after orange juice and at 0, 30 and 60 minutes after ice cream. Multivariate ANOVA was used to examine satiety as a function of beverage (orange juice vs. orange juice plus pectin), time and pectin dose. RESULTS: There were significant differences in satiety as a function of beverage (p < 0.001) and time (p < 0.001) but not pectin dose (p = 0.121). The effect lasted up to 4 hours after ingesting pectin and orange juice and for 60 minutes after a second meal consisting of ice cream. CONCLUSIONS: Pectin in doses as small as 5 g mixed with orange juice increases satiety and can aid in a program to reduce weight by limiting food intake.

Adolescent↗
PubMed1997

P450 arachidonate metabolites mediate bradykinin-dependent inhibition of NaCl transport in the rat thick ascending limb.

Recent studies from this laboratory demonstrated that bradykinin transiently elevates intracellular Ca2+ and inhibits Cl-reabsorption in the in vitro microperfused medullary thick ascending limb (mTAL) of the rat. The present study was designed to identify the intracellular signaling mechanism(s) that mediate this response. Preincubation with the intracellular calcium chelator BAPTA (10(-5) M) completely eliminated the bradykinin-dependent increase in intracellular Ca2+ and the suppression of Cl- transport. Preincubation with the cGMP-dependent protein kinase inhibitor H-89 (10(-5) M) had no effect on the transport response to bradykinin. In contrast, 17-octadecynoic acid (17-ODYA; 10(-5) M), a suicide-substrate inhibitor of renal cytochrome P450 omega-hydroxylase, completely blocked the transport response to bradykinin, while the cyclooxygenase inhibitor sodium meclofenamate (10(-5) M) had no effect. Finally, addition of the cytochrome P450 omega-hydroxylase metabolite 20-hydroxyeicosatetraenoic acid (20-HETE; 10(-8) M) to the bathing medium significantly inhibited Cl- transport in the mTAL (delta -39 +/- 6.0%; p < 0.05), while the epoxygenase metabolite 5,6-epoxyeicosatrienoic acid (5,6-EET; 10(-8) M) had no effect. These data suggest that the bradykinin-dependent inhibition of Cl- transport in the mTAL of the rat is mediated by cytochrome P450 dependent metabolite(s) of arachidonic acid.

8,11,14-Eicosatrienoic Acid↗
PubMed1996

Are all 585 nm pulsed dye lasers equivalent? A prospective, comparative, photometric, and histologic study.

BACKGROUND: Flashlamp-pumped pulsed dye lasers (585 nm) are used to treat port-wine stains and other cutaneous vascular lesions. Strikingly different tissue effects were seen after two apparently similar 585 nm pulsed dye lasers at equivalent fluences were used. OBJECTIVE: We compared the photometric and histologic effects of two apparently similar 585 nm flashlamp-pumped pulsed dye laser systems. METHODS: The burn pattern and beam profile analysis of two Candela SPTL-1 lasers and two Cynosure Photogenica V lasers were compared. Various fluences and spot sizes of the Cynosure laser were placed on normal skin and evaluated for histologic change. RESULTS: Variation between the stated area of the spot and the actual measured area of the spot was found in all lasers studied. The area of the 5 mm spot of the two Candela lasers studied was 35% and 31% larger, respectively, than the stated area. The Cynosure lasers had areas that were 8% and 4% smaller than the stated area. Neither beam profile was uniform. The Candela laser maintained a gaussian-like distribution of energy, whereas the Cynosure laser beam profile resembled a top hat with a more even distribution of energy. Histologic studies confirmed the maintenance of vascular specificity without nonspecific thermal damage. CONCLUSION: When changing from one 585 nm pulsed dye laser to another and using supposedly equivalent fluences, one cannot guarantee that clinical results will be equivalent. In an effort to achieve consistent treatments when moving between lasers manufactured by different companies, it would be prudent to place a single spot of energy onto burn paper and measure the diameter of the spot.

Blood Vessels↗
PubMed1996

Effects of thoracic volume expansion on cardiorenal function in the conscious rat.

BACKGROUND: Exposure to microgravity results in the loss of fluid and electrolytes. HYPOTHESIS: This study was designed to determine whether loss of fluid and electrolyte by the kidney occur by increased filtration or decreased tubular reabsorption and to investigate the mechanisms involved. METHODS: Vascular and bladder catheters were implanted and the effects of preferential thoracic volume expansion were studied in conscious rats using a new hindlimb supported head-down tilt model designed to simulate the effects of microgravity. Control rats maintained at 0 degree tilt (NT) were compared to rats at 40 degrees head-down tilt (HDT). RESULTS: HDT immediately increased central venous pressure from 1.4 +/- 0.3 to 2.7 +/- 0.3 mm Hg (p < 0.01); which peaked after 8 h. Compared to NT, cumulative sodium excretion significantly increased within 6 h of HDT and remained increased at 24 h (198.8 +/- 40.3 vs. 72.8 +/- 18.4 microEq; p < 0.01). HDT also significantly increased glomerular filtration rate (GFR) at both 6 (p < 0.05) and 24 h (p < 0.01). In contrast, fractional proximal reabsorption (assessed by lithium clearance) was unchanged over the period of HDT, indicating an appropriate proximal tubule response to increased filtered sodium. HDT had no significant effect on plasma catecholamine or atrial natriuretic peptide concentration nor on plasma renin, while plasma aldosterone concentration was increased after 24 h (72.8 +/- 24.0 vs. 32.4 +/- 8.7 ng/dl; p < 0.05); presumably in response to sodium loss during HDT. CONCLUSION: HDT-induced thoracic volume expansion significantly increases sodium excretion, primarily as a result of an increase in GFR.

Analysis of Variance↗
PubMed1994

Modulation of cyclic AMP metabolism by protein kinase C in PC18 cells.

The present study examined the effect of protein kinase C (PKC) on cyclic AMP metabolism in PC18 cells, a recently developed model of the adrenal medullary chromaffin cell. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) significantly potentiated cAMP accumulation in response to the adenosine analog N6-R-phenyl-isopropyl adenosine (PIA) and to forskolin. The degree of potentiation of both PIA and forskolin-stimulated cAMP levels was significantly reduced but not completely eliminated when cells were incubated in the presence of the cAMP-phosphodiesterase (cAMP-PDE) inhibitor Ro20-1724. PMA pretreatment had no detectable effect on either cytosolic or membrane-bound low Km cAMP-PDE activity, but did significantly potentiate PIA-dependent adenylate cyclase activity. We conclude that the potentiation of agonist-dependent cAMP accumulation by PKC in intact PC18 cells is due to both an enhancement of cAMP biosynthetic capacity, as well as a suppression of cAMP catabolic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Acute effects of gentamicin on thick ascending limb function in the rat.

It is well established that the aminoglycoside antibiotics can adversely affect proximal tubule function. Predominantly indirect evidence suggests that aminoglycosides may also affect function of more distal nephron segments. The present study utilized whole kidney clearance, in vivo micropuncture and in vitro microperfusion to directly determine whether acute gentamicin treatment affects sodium chloride transport in the thick ascending limb of the loop of Henle. Gentamicin (25 mg/kg) significantly increased urine flow, as well as sodium, potassium and chloride excretion within 15 min of intravenous injection. Glomerular filtration rate and proximal tubule fluid reabsorption were not altered by acute gentamicin treatment. In contrast, both fractional and absolute loop chloride transport was significantly decreased. In the in vitro microperfused medullary thick ascending limb, luminal but not basolateral administration of gentamicin (1 mM) significantly decreased chloride reabsorption when compared to time controls. These data suggest that the increased urine and electrolyte excretion associated with acute gentamicin treatment is, at least in part, a consequence of decreased transport in the thick ascending limb of Henle's loop.

Animals↗
PubMed1994

Two approaches for assessing human safety of disperse blue 1.

Disperse Blue 1 is an anthraquinone dye used at low levels in semipermanent hair color formulations. Dietary administration of Disperse Blue 1 in a National Toxicology Program (NTP) carcinogenesis bioassay produced transitional- and squamous-cell tumors, leiomyomas, and leiomyosarcomas of the urinary bladders of male and female F344/N rats. The occurrence of tumors in the urinary bladder of rats was associated with urothelial hyperplasia and the presence of urinary calculi. Despite the occurrence of urinary bladder calculi and other nonneoplastic changes, there was no evidence of urinary bladder carcinogenesis in B6C3F1 mice fed Disperse Blue in the diet for up to 2 years. A study conducted in rats of the same strain by Burnett and Squire confirmed the occurrence of calculi and transitional-cell neoplasms in the rat bladder. However, no mesenchymal-cell tumors were detected at a comparable dietary level. Further, Burnett and Squire found evidence of reversibility of the proliferative changes in the rat urinary bladder following cessation of treatment at 6 months. Disperse Blue 1 has been tested in a variety of in vivo and in vitro genotoxicity assays and was negative in vivo but produced a weak and mixed pattern of genotoxic responses in vitro which may be attributable to a constituent of the commercial preparations. Evaluation of the available data for Disperse Blue 1 and comparison with the responses observed in the urinary bladders of rats administered other rodent bladder carcinogens considered to act through a secondary mechanism indicate that a threshold approach is appropriate for assessing risk. With this approach, an uncertainty factor of 1000 applied to the no-observed-adverse-effect level in the NTP bioassay yielded a safe exposure level of 45-56 micrograms/kg/day. In contrast, with a conventional quantitative risk assessment approach, the exposure level corresponding to an upper limit on lifetime risk of 10(-6) to 10(-5) was 0.39 to 3.9 micrograms/kg/day, respectively. The safe level of Disperse Blue 1 derived using the threshold approach is approximately 20 times greater than the maximum average daily applied dose of 2.7 micrograms/kg/day associated with its use in semipermanent hair color formulations, while the exposure associated with the 10(-5) risk level using the linearized multistage model in the conventional approach was determined to be 1.5 times greater. Because oral absorption is substantially more than dermal absorption, the actual margin of safety is most likely much greater than either of these comparisons suggests.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Modulation of cyclic AMP metabolism by glucocorticoids in PC18 cells.

Glucocorticoids modulate signal transduction mechanisms in a number of cell systems. As the adrenal medulla is exposed to relatively high levels of adrenal cortical glucocorticoids in vivo, particularly during periods of stress, the aim of the present study was to determine whether glucocorticoids modulate cyclic AMP (cAMP) metabolism in an in vitro model of this system, the PC18 cell line. Dexamethasone significantly potentiated cAMP accumulation in response to the adenosine analogue N6-R-phenylisopropyl adenosine (PIA), and in response to forskolin. This effect was both time- and concentration-dependent. Maximal potentiation was observed after 48 h of exposure to 1 microM dexamethasone. Corticosterone and to a lesser extent aldosterone also significantly potentiated PIA-dependent cAMP accumulation. In contrast, estradiol, testosterone, and triiodothyronine had no potentiative effect. Potentiation could be eliminated by coincubation with the protein synthesis inhibitor cycloheximide. In the presence of Ro 20-1724, a cAMP-phosphodiesterase inhibitor, the degree of potentiation of both PIA- and forskolin-dependent cAMP accumulation was significantly decreased by 50-60%. These data suggested that altered cAMP-phosphodiesterase activity may be involved in this response. However, cytosolic and membrane-bound low Km cAMP-phosphodiesterase activity was unchanged in dexamethasone-treated cells compared with controls. Similarly, there were no significant differences in basal, PIA-, forskolin-, or GTP gamma S-stimulated adenylate cyclase activities between groups. These studies indicate that glucocorticoids can potentiate cAMP accumulation in intact PC18 cells. The mechanism underlying this potentiation is likely to be multifactorial, but may be due in part to decreased cAMP catabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Papulonodular dermal mucinosis in systemic lupus erythematosus.

A 38-year-old woman with systemic lupus erythematosus presented to the dermatology department with diffuse nodules and plaques on her face, trunk and extremities. A lesional biopsy revealed large dermal mucin deposits. Papulonodular dermal mucinosis is characterized histologically by diffuse dermal mucin without the classic epidermal or inflammatory changes seen in lupus erythematosus (LE). This rare variant of LE should be distinguished from other cutaneous mucinoses.

Adult↗
PubMed1993

Effects of transforming growth factor beta and interleukin-1 beta on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture.

Experiments were conducted to determine the roles of the rate limiting enzymes, cyclooxygenase 1 and 2 (COX1 and COX2) and cytoplasmic phospholipase A2 (PLA2), in transforming growth factor beta (TGF-beta) and interleukin-1 (IL-1 beta) activated prostaglandin synthesis. Results show that TGF-beta increases steady state levels of COX1 mRNA in both human embryo lung fibroblasts (IMR90) and calf pulmonary artery endothelial cells (BPAEC). Temporal experiments show that TGF-beta increases, within 2hrs, a 5.5kb COX1 in IMR90 and the 2.7kb COX1 mRNA in BPAEC. IL-1 beta increases COX1 mRNA only in IMR-90, not BPAEC. COX2 mRNA, under basal conditions, is not detected in BPAEC and is expressed only marginally in IMR90. TGF-beta or IL-1 beta have no effect on expression of COX2 gene in either cell type. IL-1 beta increases steady state levels of PLA2 mRNA in both IMR90 and BPAEC while TGF-beta increases expression of the PLA2 gene only in BPAEC. Time experiments with TGF-beta show induction of PLA2 mRNA within 1hr, peaking at 4hrs. PG synthesis in response to the cytokines was determined in IMR90 and BPAEC to further assess the significance of the above results. TGF-beta increases the synthesis of prostacyclin in BPAEC in a time related fashion peaking at 8hrs at 13 fold above basal. To focus on the action of COX1 and bypass the action of PLA2, exogenous arachidonic acid was used as substrate for PG synthesis. In these experiments IL-1 beta increases PGE2 synthesis 8 fold in IMR90 while IL-1 beta and TGF-beta added simultaneously increases PGE2 synthesis 25 fold. These results in sum illustrate that the cytokines, TGF-beta and IL-1 beta, regulate both COX1 and PLA2 mRNA levels. Furthermore, this regulation appears coordinated to bring about elevation of prostaglandin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Functional expression of the bradykinin-B2 receptor cDNA in Chinese hamster lung CCL39 fibroblasts.

The bradykinin (BK) B2 receptor cDNA was synthesized by rt-PCR and transfected into the Chinese hamster lung fibroblasts, CCL39. The CCL39 do not contain the mRNA for this receptor and do not bind BK. Clones of transfected cells were screened for BK receptor mRNA, binding of BK, and for [Ca2+]i response to BK. The clones showed various levels of receptor mRNA. Scatchard analysis of three clones, B6, B5 and B1, each gave a Kd of approximately 1.0nM while the Bmax for each clone differed at 320, 38.7, and 5.39 fmoles per 10(6) cells respectively. The [Ca2+]i response of the three clones to BK decreased with the receptor number/cell. Thus, levels of mRNA, BK binding and [Ca2+]i response proved proportionally related in the transfected clones. The actions of BK and alpha-thrombin, which has an endogenous receptor in these cells, were assessed in clone B6. BK proved active but also distinct from thrombin. BK at 10nM and thrombin at 2units/ml both effectively increased cytosolic [Ca2+]i. BK at 10nM stimulated PGE2 production three fold over basal, while thrombin only marginally elevated PGE2 levels. Alone, BK stimulated a small increase in 3H-thymidine incorporation into DNA. However, in combination with insulin, BK stimulated DNA synthesis to 76% of thrombin, a potent mitogen in these cells. These results illustrate that the BK-B2 receptor cDNA can be stably transfected into a mammalian cell and can activate transmembrane signalling pathways.

Animals↗
PubMed1992

In-situ hybridization of tropoelastin mRNA during the development of the multilayered neonatal rat aortic smooth muscle cell culture.

Cultured neonatal rat aortic smooth muscle cells are active in synthesizing and depositing large amounts of elastin in their extracellular matrix, making this an ideal system for studying elastogenesis. In this study, the ability of individual cells to synthesize tropoelastin was examined by in-situ hybridization methods. One-micron semi-thin epoxy resin-embedded transverse sections of cells cultured 1, 2, 3 and 4 weeks showed an increase with time in both the number of cells with hybridization signal and the signal intensity; tropoelastin mRNA hybridization signal intensity decreased thereafter up to 8 weeks in culture. In longitudinal sections through the early cultures (1-week), we observed mitotic cells with no detectable hybridization signal, and non-mitotic cells with either no, little or high signal intensity. These data suggest that mitotic cells do not synthesize tropoelastin, and that there is a strong correlation between the hybridization signal intensity and the rate of tropoelastin synthesis. These data also suggest in-situ hybridization methods can detect which cell(s) contain tropoelastin mRNA, their location in the multilayer, and variations in signal intensity. We conclude it is possible to correlate hybridization signal intensity with variations of tropoelastin mRNA levels within individual cells of the cultured smooth muscle cell multilayer.

Animals↗
PubMed1991

Effect of ultrasound therapy on the repair of Achilles tendon injuries in rats.

The purpose was to determine the effects of selected regimens of ultrasound therapy on the rates of repair of injured Achilles tendons of rats. Specific dependent variables examined were tendon breaking strength and rate of collagen formation. A puncture technique was used to induce injuries to both Achilles tendons of rats. Continuous ultrasound was administered to the left tendon for 4 min per treatment session at an intensity of 1.5 W.cm-2. Rats were sacrificed 2, 5, 9, 15, and 21 d following injury for measurement of tendon breaking strength and 3 and 5 d postinjury for analysis of collagen synthesis. Breaking strength was defined as the minimum force required to completely rupture the tendon. Collagen synthesis was indicated by the conversion of labeled proline to hydroxyproline. The breaking strengths of the treated tendons were significantly greater than strengths of the untreated tendons 5, 9, 15, and 21 d postinjury. Collagen synthesis was increased in the treated tendons compared with the untreated tendons 5 d postinjury. The results indicate that ultrasound treatment increases the rate of repair of injured Achilles tendons of rats. The results are also consistent with an association between increased collagen synthesis and greater breaking strength during tendon repair.

Achilles Tendon↗
PubMed1990

Experience with a physiology workshop for high school and college teachers.

Science education in the United States at all academic levels is widely perceived to need direct assistance from professional scientists. The current dearth of quality applicants from this country to medical and graduate schools suggests that our existing undergraduate and high school science curriculum is failing to provide the necessary stimulus for gifted students to seek careers in the health sciences. Recognizing the need to become more directly helpful to high school and college science teachers, members of the faculty of the Department of Physiology and Biophysics at the University of Kentucky College of Medicine held a 5.5-day Physiology Summer Workshop during June, 1989. Participants included 25 college teachers from Kentucky and 5 other states plus 22 Kentucky high school teachers. The presence of the two levels of educators provided communication about curricular concerns that would be best addressed by mutual action and/or interaction. Each day's activities included morning lectures on selected aspects of organ system and cellular physiology, a series on integrative physiology, and afternoon laboratory sessions. The laboratory setting allowed the instructor to expand on principles covered in lecture as well as provided the opportunity for in-depth discussion. A selection of evening sessions was presented on 1) grants available for research projects, 2) obtaining funds for laboratory equipment, and 3) graduate education in physiology.

Capital Financing↗
PubMed1988

Modulation of vasopressin-sensitive cyclic AMP levels by calcium in papillary collecting tubules.

The present study was designed to examine the extent to which calcium modulates vasopressin (AVP)-stimulated cyclic AMP (cAMP) accumulation in microdissected rat papillary collecting ducts (PCD), and to identify the mechanism(s) involved. Using a submaximal concentration of vasopressin (1 nM), ionophore A23187-mediated increases in intracellular calcium inhibited AVP-dependent cAMP levels by 69% (P less than 0.001) in the absence of the cAMP-phosphodiesterase inhibitor 1-methyl-3-isobutyl xanthine (MIX). The degree of inhibition was significantly reduced (-47%; P less than 0.01) in the presence of MIX. Compared to controls (1.2 mM calcium), AVP-sensitive cAMP accumulation was significantly reduced (-34%; P less than 0.05) when PCD were incubated in a medium containing an increased (5.0 mM) calcium concentration. In the presence of MIX 5.0 mM calcium had no effect on cAMP levels. Conversely, compared to controls, a calcium-free medium increased AVP-dependent cAMP accumulation by 89% (P less than 0.01) in the absence of MIX, and similarly by 82% (P less than 0.05) in the presence of MIX. These data demonstrate that calcium can modulate AVP-dependent cAMP accumulation in PCD as a result of effects on both adenylate cyclase and cAMP phosphodiesterase activities.

3',5'-Cyclic-AMP Phosphodiesterases↗