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Biomedical subjects

C A Jones

Publications and source records attributed to C A Jones.

At least 55 records · Page 3Linked to original sources
PubMed2001

Rapid accumulation of phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate correlates with calcium mobilization in salt-stressed arabidopsis.

The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] is a key signaling molecule in animal cells. It can be hydrolyzed to release 1,2-diacyglycerol and inositol 1,4,5-trisphosphate (IP(3)), which in animal cells lead to protein kinase C activation and cellular calcium mobilization, respectively. In addition to its critical roles in constitutive and regulated secretion of proteins, PtdIns(4,5)P(2) binds to proteins that modify cytoskeletal architecture and phospholipid constituents. Herein, we report that Arabidopsis plants grown in liquid media rapidly increase PtdIns(4,5)P(2) synthesis in response to treatment with sodium chloride, potassium chloride, and sorbitol. These results demonstrate that when challenged with salinity and osmotic stress, terrestrial plants respond differently than algae, yeasts, and animal cells that accumulate different species of phosphoinositides. We also show data demonstrating that whole-plant IP(3) levels increase significantly within 1 min of stress initiation, and that IP(3) levels continue to increase for more than 30 min during stress application. Furthermore, using the calcium indicators Fura-2 and Fluo-3 we show that root intracellular calcium concentrations increase in response to stress treatments. Taken together, these results suggest that in response to salt and osmotic stress, Arabidopsis uses a signaling pathway in which a small but significant portion of PtdIns(4,5)P(2) is hydrolyzed to IP(3). The accumulation of IP(3) occurs during a time frame similar to that observed for stress-induced calcium mobilization. These data also suggest that the majority of the PtdIns(4,5)P(2) synthesized in response to salt and osmotic stress may be utilized for cellular signaling events distinct from the canonical IP(3) signaling pathway.

Arabidopsis↗
PubMed2001

Mast cell tryptase activates extracellular-regulated kinases (p44/p42) in airway smooth-muscle cells: importance of proteolytic events, time course, and role in mediating mitogenesis.

We previously reported that mast cell tryptase is a potent mitogen for cultured airway smooth-muscle cells, but the early intracellular signals mediating this response are not known. In many cells, proliferative effects are mediated by a mitogen-activated protein kinase signaling pathway involving Raf-1, MAP kinase kinases (MEKs), and extracellular signal-regulated protein kinases (ERKs) 1 and 2. Therefore, we tested for tryptase-induced activation of ERK1 and 2 in cultured dog tracheal smooth-muscle cells. Tryptase, in nanomolar concentrations which potently stimulated DNA synthesis, increased dual phosphorylation of ERKs in cellular lysates as well as ERK2 kinase activity in immunoprecipitates. Pretreatment of cells with the MEK inhibitor PD098059 abolished tryptase-induced increases in DNA synthesis and attenuated increases in ERK2 activity. Irreversible inhibition of tryptase's proteolytic activity, using p-amidino phenylmethanesulfonyl fluoride, attenuated tryptase-induced increases in DNA synthesis and dual phosphorylation of ERKs by 76% and 40 to 60%, respectively. Tryptase also increased c-fos transcription as quantified in polymerase chain reactions. In concentrations that caused similar increases in DNA synthesis, tryptase and platelet-derived growth factor (PDGF-BB) increased ERK activity (and c-fos transcription) with markedly different kinetics, the tryptase-induced responses being slower in onset and more sustained. We conclude that tryptase-induced mitogenesis in airway smooth-muscle cells requires activation of ERK1 and 2; that these responses depend partially, but not completely, upon tryptase's properties as a protease; and that they are slower in onset and more sustained than those induced by PDGF-BB.

Animals↗
PubMed2001

The production of novel sordarin analogues by biotransformation.

The biotransformation of the fungal protein synthesis inhibitor sordarin is reported. Nine taxonomically diverse organisms supported the isolation and identification of twelve modified products. The structural diversity of the biotransformation products observed and their value in supporting further chemistry is discussed.

Antifungal Agents↗
PubMed2001

Exercise combined with continuous passive motion or slider board therapy compared with exercise only: a randomized controlled trial of patients following total knee arthroplasty.

BACKGROUND AND PURPOSE: The primary purpose of this randomized controlled trial was to determine which method of mobilization - (1) standardized exercises (SE) and continuous passive motion (CPM), (2) SE and slider board (SB) therapy, using an inexpensive, nontechnical device that requires minimal knee active range of motion (ROM), or (3) SE alone-achieved the maximum degree of knee ROM in the fIrst 6 months following primary total knee arthroplasty (TKA). The secondary purpose was to compare health-related quality of life among these 3 groups. SUBJECTS: The subjects were 120 patients (n=40/group) who received a TEA at a teaching hospital between June 1997 and July 1998 and who agreed to participate in the study. METHODS: Subjects were examined preoperatively, at discharge, and at 3 and 6 months after surgery. The examination consisted of measurement of knee ROM and completion of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: The 3 treatment groups were similar with respect to age, sex, and diagnosis at the start of the study. There were no differences in knee ROM or in WOMAC Osteoarthritis Index or SF-36 scores at any of the measurement intervals. The rate of postoperative complications also was not different among the groups. DISCUSSION AND CONCLUSION: When postoperative rehabilitation regimens that focus on early mobilization of the patient are used, adjunct ROM therapies (CPM and SB) that are added to daily SE sessions are not required. Six months after TEA, patients attain a satisfactory level of knee ROM and function.

Activities of Daily Living↗
PubMed2001

Use of vitamins, minerals and herbs: a survey of patients attending family practice clinics.

OBJECTIVE: To examine the use of vitamin, mineral and herbal supplements in patients attending family practice clinics. DESIGN: A prospective 1-year cohort study. SETTING: Sixteen family practices in Calgary. PARTICIPANTS: One hundred and eighteen patients (more than 18 years of age) were initially interviewed; 12 patients were lost to follow-up. MAIN OUTCOME MEASURES: Number and type of supplements used, duration of use, sources of patient information, beliefs about supplement efficacy and safety, reporting use to physicians, costs and changes in pattern of use over 1 year. RESULTS: Supplement use was unrelated to age, but more women (73%) used supplements than men (44%). Relative to age, more patients younger than 50 years believed supplements were safer than prescription medications (82% v. 43%, p = 0.0005). Younger patients were less likely than those over 50 years old to have received supplement information from physicians (10% v. 37%, p = 0.0008) and were less compliant than older patients with manufacturers' recommended dosages (p = 0.02). Whereas 74% of those over the age of 50 years informed their physician that they used supplements, only 30% of younger patients did so (p = 0.0006). At 1-year follow-up, the number of supplements taken per patient increased (p < 0.05), and there was a tendency for more patients to take supplements (61% v. 70%, p = NS). CONCLUSIONS: The majority of patients attending family practices in Calgary use vitamin, mineral or herbal supplements, and monitoring of supplement use by health care professionals is minimal. Young patients, in particular, tend not to report their use of supplements. They also believe the supplements are safer and more effective than prescription medications and obtain information from nonmedical sources. Physicians should enhance patient understanding of these products and include supplement use in all medical histories. In particular, younger patients require more reliable information on supplements.

Alberta↗
PubMed2001

An update: women, hypertension and therapeutic efficacy.

One in five Canadians has high blood pressure. The prevalence is as high as 58% in women between the ages of 65 and 74 years. Approximately 40% of stroke cases, 39% of myocardial infarction cases and 28% of end stage renal diseases are attributable to hypertension. Despite the burden that hypertension places on women, the effect of antihypertensive therapy on cardiovascular complications has not been well established. To address this knowledge gap, two meta-analyses with sex-specific results, including the most current randomized, controlled trials to evaluate hypertension treatment, were reviewed. The Individual Data Analysis of Antihypertensive (INDANA) intervention trials group and Quan and colleagues analyzed treatment benefits in 23,000 women and 19,975 men according to subgroup meta-analyses from 12 randomized, controlled trials that compared antihypertensive drug therapy with placebo. The meta-analyses demonstrated a statistically significant treatment benefit for all of the reported clinical outcomes in men of all ages and in black women. In women over the age of 54 years, antihypertensive treatment was associated with a significant reduction of fatal and nonfatal stroke, cardiovascular events and cardiovascular mortality. Overall, there was no significant difference in the relative treatment benefit in women and men; however, the absolute treatment benefit was lower in women than in men. Thus, the number needed to treat for the end points of fatal stroke, nonfatal stroke and cardiovascular events was one- to threefold higher for women than for men. Furthermore, white women between the ages of 30 and 54 years showed no treatment benefit or harm. Data from the 6.7-year follow-up in the Hypertension Detection and Follow-up Program (HDFP) trial suggested that this group of younger women might benefit from a longer duration of treatment. Indications for pharmacological intervention seem quite clear for all subgroups, excluding these younger women. Until further evidence is available for this low risk subgroup, the current recommendations for lifestyle modification cannot be challenged.

Adult↗
PubMed2000

Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model.

We used a mouse nasal model of herpes simplex virus 2 (HSV-2) infection to examine the biological properties of HSV-2 wild-type (wt), TK-negative, and replication-defective strains in vivo. Nasal septa tissue is the major site of wt viral replication post intranasal (i.n.) inoculation. The HSV-2 strain 186 syn(+)-1 wt virus caused lethal encephalitis at doses of 10(4) PFU and above per nostril, and at lower doses no neurons in the trigeminal ganglia were positive for the latency-associated transcript, indicating a lack of latent infection. The 186DeltaKpn TK-negative mutant virus replicated in nasal septa tissue but showed low-level replication in trigeminal ganglia at only one timepoint. In situ hybridization of trigeminal ganglia showed that the number of LAT-positive neurons was proportional to the inoculum dose from 10(3) to 10(6) PFU per nare. The replication-defective mutant virus 5BlacZ showed no replication in nasal septa tissue and no persistence of viral DNA at the inoculation site or the trigeminal ganglia. Nevertheless, inoculation of 5BlacZ or the double-mutant dl5-29 at distal sites reduced acute replication and latent infection of 186DeltaKpn following intranasal challenge. This infection model provides a biological system to test the properties of HSV-2 strains and shows that replication-defective mutant strains do not persist at sites of inoculation or in sensory ganglia but can induce immune protection that reduces the latent viral load of a challenge virus.

Animals↗
PubMed2000

Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood.

Mononuclear cells in umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs in utero is unknown. We investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (> or =37 weeks of gestation). Der p 1 was detectable in 24 of 43 amniotic fluid samples where it was also present in maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 in the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.

Amniotic Fluid↗
PubMed2000

Expression of a renin/GFP transgene in mouse embryonic, extra-embryonic, and adult tissues.

A reporter construct was assembled with 4-kb of renin 5'-flanking sequence fused to humanized green fluorescent protein (GFP) cDNA. Transgenic mice carrying this construct were produced and assayed for GFP expression. In the adult, expression was detected in juxtaglomerular (JG) cells of the kidney and granular convoluted tubular cells of the submandibular gland. Furthermore, treatment of mice with captopril induced GFP expression in renal vascular smooth muscle cells. During embryogenesis, GFP expression was first detected at embryonic day E13 in the adrenal gland and Wolffian duct. Expression was also seen in the developing renal vasculature as early as E14 and remained detectable through birth. Renal GFP expression became restricted to JG cells in adults. Fetal adrenal and gonadal arteries also expressed GFP. In the placenta, GFP was observed in giant cell trophoblasts, consistent with reports of renin expression in chorionic cells of both humans and mice. We conclude that 4 kb of renin 5' flank is sufficient to direct multiple known renin expression patterns. Furthermore, the renin-GFP construct characterized here will provide a useful vital reporter for renin expression.

Aging↗
PubMed2000

Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression.

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.

Animals↗
PubMed2000

Changes in REM sleep occurrence due to rhythmical auditory stimulation in the rat.

The effects of the rhythmical delivery of an auditory stimulus (1000 Hz, from 50 to 100 dB, 20 ms, every 20 s) on the pattern of rapid eye movement (REM) sleep occurrence was studied in the rat. The stimulation was simultaneously carried out on pairs of rats over 5 consecutive days (10-h recording sessions), during which a tone of increasing intensity (50, 63, 75, 88, 100 dB) was used. In each experimental session, auditory stimulation was triggered by the REM sleep occurrence of one rat (REMS-selective stimulation) whilst the other rat simultaneously received the same stimuli, but during any stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the total amount of REM sleep in the 10-h recording session was increased over the 5 days of stimulation in the REMS-unselective group. This effect was due to an increase in the mean duration of REM sleep episodes. However, no significant changes were observed in animals under REMS-selective stimulation, nor in a third group of animals in which the spontaneous evolution of REM sleep occurrence (REMS-spontaneous) was studied. Since 86% of the stimuli under the REMS-unselective auditory stimulation fell outside REM sleep, the result would suggest that REM sleep occurrence is affected when the stimuli are delivered during a time period (i.e. during wakefulness or non-REM sleep) in which it is well known that physiological regulations are fully operant.

Acoustic Stimulation↗
PubMed2000

Prenatal origins of allergic disease.

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease.

Antibody Formation↗
PubMed2000

Body size, dose of hemodialysis, and mortality.

This study investigates the role of body size on the mortality risk associated with dialysis dose in chronic hemodialysis patients. A national US random sample from the US Renal Data System was used for this observational longitudinal study of 2-year mortality. Prevalent hemodialysis patients treated between 1990 and 1995 were included (n = 9,165). A Cox proportional hazards model, adjusting for patient characteristics, was used to calculate the relative risk (RR) for mortality. Both dialysis dose (equilibrated Kt/V [eKt/V]) and body size (body weight, body volume, and body mass index) were independently and significantly (P < 0.01 for each measure) inversely related to mortality when adjusted for age and diabetes. Mortality was less among larger patients and those receiving greater eKt/V. The overall association of mortality risk with eKt/V was negative and significant in all patient subgroups defined by body size and by race-sex categories in the range 0.6 < eKt/V < 1.6. The association was negative in the restricted range 0.9 < eKt/V < 1.6 (although not generally significant) for all body-size subgroups and for three of four race-by-sex subgroups, excepting black men (RR = 1. 003/0.1 eKt/V; P > 0.95). These findings suggest that dose of dialysis and several measures of body size are important and independent correlates of mortality. These results suggest that patient management protocols should attempt to ensure both good patient nutrition and adequate dose of dialysis, in addition to managing coexisting medical conditions.

Adult↗
PubMed2000

Pre-natal sensitization in humans.

Allergy has a very strong hereditary component but even in identical twins, concordance for the development of allergic disease can be as low as 50%. This suggests that there is a very strong environmental influence on manifestations of sensitization. To what extent environment might have an influence on the ontogeny of sensitization antenatally has hitherto not been a focus of much research. However, circumstantial evidence suggests that this may be important.

Allergens↗
PubMed2000

Functional characterization of the P2X(4) receptor orthologues.

1. The aim of this study was to functionally characterize the recombinant mouse P2X(4) receptor and to compare its pharmacological properties with those of the human and rat orthologues. 2. Whole cell recordings were made from rafts of HEK-293 cells stably expressing recombinant mouse, rat or human P2X(4) receptors, using Cs-aspartate containing electrodes (3 - 8 MOmega) in a HEPES-buffered extracellular medium. 3. The agonist potency of ATP at the three species orthologues was similar, with mean EC(50) values of 2.3 microM, 1.4 microM and 5.5 microM, respectively. 4. Adenosine-5'-tetraphosphate (AP4) acted as a partial agonist with respect to ATP at the mouse and human P2X(4) receptors (EC(50)=2.6 and 3.0 microM), but was significantly less potent at the rat orthologue (EC(50)=20.0 microM). alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) also acted as a partial agonist, producing 29% of the maximum response at the mouse P2X(4) and 24% at the human P2X(4) receptor. 5. In contrast to the other species orthologues, alpha,beta-meATP failed to elicit a significant agonist response at rat P2X(4) receptors, and was found to act as an antagonist, with an IC(50) of 4.6 microM, against 10 microM ATP. 6. Mouse P2X(4) receptors were found to be sensitive to the antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (IC(50)=10.5 microM), as were human P2X(4) receptors (IC(50)=9.6 microM). The rat receptor however, showed a low sensitivity to PPADS (IC(50)>100 microM). 7. All three orthologues were relatively suramin-insensitive (IC(50)>100 microM) and insensitive to 1-[N, O-Bis(5-isoquinoline sulphonyl)benzyl]-2-(4-phenylpiperazine)ethyl]-5-isoquinoline sulphonamide (KN-62; IC(50)>3 microM). 8. Our results suggest that the pharmacological properties of the mouse receptor are most similar to the human P2X(4) receptor, and differ markedly from the rat receptor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗