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Biomedical subjects

C A Walsh

Publications and source records attributed to C A Walsh.

85 records · Page 5Linked to original sources
PubMed1994

A novel bombesin receptor antagonist selectively blocks the satiety action of peripherally administered bombesin.

To investigate the effect of a new, specific antagonist for bombesin receptors on the satiating action of exogenous bombesin, adult male rats were adapted to a nondeprivation test regimen with daily access to a palatable liquid food. In a prefeeding paradigm, rats received intraperitoneal injections of the bombesin receptor antagonist, BW2258U89 (6.25, 25, 50, or 100 micrograms kg-1) or vehicle 20 min before, and then a second injection of either bombesin (4 micrograms kg-1), gastrin-releasing peptide (GRP; 16 micrograms kg-1), the C-terminal octapeptide of cholecystokinin (CCK-8; 4 micrograms kg-1), or vehicle 5 min before a 2-h feeding test. BW2258U89 pretreatment antagonized the satiating actions of bombesin and GRP18-27 in a very potent, dose-related manner, but did not antagonize the satiating action of CCK-8. These differential results with BW2258U89 are consistent with prior results showing the potency of this antagonist for bombesin receptor-mediated effects in visceral systems; in addition, they demonstrate the selectivity of the compound for the satiating actions of peripherally administered bombesin and bombesin-like peptides.

Animals↗
PubMed1994

Primary cultures of human bone-derived cells produce parathyroid hormone-related protein: a study of 40 patients of varying age and pathology.

Parathyroid hormone-related protein (PTHrP), a mediator of hypercalcemia of malignancy, has been detected in many tumours and in some normal foetal and adult tissues. PTHrP has potent effects on bone turnover in vivo and in vitro. In this study we cultured cells derived from explants of bone obtained from 40 subjects (age range 2-88 years). Immunoreactive PTHrP (iPTHrP) was detected by immunoradiometric assay (IRMA) in conditioned medium from 25 of 40 cultures of bone-derived cells. PTHrP mRNA was detected in bone-derived cells by reverse transcriptase-linked polymerase chain reaction (RT-PCR). The identity of PCR products was confirmed by Southern blotting. Local production of PTHrP in vivo may be important in the regulation of bone growth and remodelling.

Adolescent↗
PubMed1993

PCR detection of cytokines in normal human and pagetic osteoblast-like cells.

We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta, IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-alpha was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-alpha was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.

Base Sequence↗
PubMed1992

Evidence for P2-purinoceptors on human osteoblast-like cells.

ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions.

Adenosine Triphosphate↗
PubMed1991

Application of reflected light microscopy to identify and quantitate resorption by isolated osteoclasts.

A simple technique has been developed to identify the resorption lacunae excavated by avian osteoclasts in vitro. Briefly, devitalized bovine bone wafers, with cells in situ, are fixed, stained with toluidine blue, and then examined by reflected light microscopy. Resorption pits are clearly visible using a x 10 objective, even when the resorbed areas are covered by a confluent layer of cells. The technique can be used to quantify the plan area, depth, and volume of the excavations. Depth and volume are assessed using the x 50 objective lens. This technique has been used to investigate the effects of retinyl acetate and EHDP on bone resorption.

Animals↗
PubMed1991

Aerobic responses to walking training in sedentary adolescents.

Promotion of physical fitness and an active lifestyle is critical during the formative adolescent years. This study investigated the effect of a school-based, alternative physical education program of walking training on the aerobic fitness of sedentary, predominantly obese teenagers. The subjects trained three days a week for 11 weeks at an average pace of 3.9 mph and heart rate of 151 beats per minute (79.6% of maximum). Physiologic responses during maximal treadmill testing before and after walking training were compared to those during a 3-month control period preceding the program. Weight-relative maximal oxygen uptake improved 9.9 percent (p less than .05), while treadmill endurance time increased by two minutes (23 percent, p less than .05). These findings indicate that small but significant improvements in aerobic function can be expected from walking training in sedentary adolescents.

Adolescent↗
PubMed1990

The effects of extracellular pH on bone resorption by avian osteoclasts in vitro.

It has previously been reported that low extracellular pH stimulates the excavation of resorption lacunae by rodent osteoclasts in vitro. Using avian bone cells in a similar in vitro assay we have demonstrated that osteoclast activity is optimal at pH 7.20-7.40 and is inhibited at extremes of pH (less than 7.10 and greater than 7.60). Over the first 24 h of incubation at low pH there may be an increase in osteoclastic resorption but to a lesser extent than that reported for rodent cells. However, after 24-30 h in culture there is little or no further increase in bone resorption, presumably due to a cytotoxic effect of low pH acting either on the osteoclast directly or via nonosteoclastic bone cells. In contrast to a previous report, in which preincubation of wafers for 24 h had no effect on bone resorption, we found that preincubation of bone substrates at pH 6.50 for longer periods enhances subsequent resorption at pH 7.20.

Animals↗
PubMed1990

Differentiation of sinus rhythms from supraventricular tachydysrhythmias by activation sequence and timing.

Implantable device detection of tachydysrhythmias remains unreliable and inexact. False responses may occur because of misinterpretation of sinus tachycardia (ST) as a supraventricular tachydysrhythmia (SVTD). Timing of atrioventricular (AV) activation and ventricular dispersion identified and discriminated between ST and SVTDs in 11 dogs. Three bipolar epicardial electrodes recorded left atrial and left and right ventricular depolarizations simultaneously during normal sinus rhythm (NSR) (mean of 5 beats in 11/11 dogs), ST produced by phlebotomy (50 beats in 10 episodes in 6/11) or isoproterenol infusion (105 beats in 21 episodes in 10/11), sinus bradycardia (SB) produced by vagal stimulation (140 beats in 29 episodes in 10/11), and during atrial flutter (AFL) (15 beats in 3 episodes in 3/11) and atrial fibrillation (AF) (152 beats in 31 episodes in 9/11) induced by programmed electrical stimulation. During lidocaine infusion, NSR (55 beats in 11 episodes in 10/11 dogs), SB (84 beats in 17 episodes in 7/11), AFL (10 beats in 2 episodes in 1/11), and AF (103 beats in 21 episodes in 7/11) were recorded. During isoproterenol infusion, SB (45 beats in 9 episodes in 5/11), AFL (15 beats in 3 episodes in 2/11), and AF (64 beats in 13 episodes in 5/11) were recorded in addition to ST. The interval between the left atrial and left ventricular intrinsic deflections (A-V1) and between the left and right ventricular intrinsic deflections (V1-V2) of each beat was measured. The mean value (msec) of A-V1 and V1-V2 in each episode was compared to NSR in the same dogs. A difference of greater than or equal to 16 ms was used for differentiation. In all cases except SB with first-degree AV block, V1-V2 in each episode was insignificant (0-14 msec), categorizing the rhythms as supraventricular. During NSR, ST and SB without AV block, delta A-V1 was small (0-15 msec). In contrast delta A-V1 was greater than or equal to 16 ms in 6/8 episodes of AFL. The remaining two episodes could be differentiated by the greater number of atrial versus ventricular beats. AF could be detected by the variability of A-V1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Differentiation of arrhythmias in the dog by measurement of activation sequence using an atrial and two ventricular electrodes.

Timing of atrioventricular activation and ventricular dispersion identifies and discriminates between beats of different origin. In eight dogs, three bipolar epicardial electrodes recorded left atrial and left and right ventricular depolarizations simultaneously during arrhythmias induced by programmed electrical stimulation and coronary artery occlusion and release. The interval between the left atrial and left ventricular intrinsic deflections (A-V1) and between the left ventricular and right ventricular intrinsic deflections (V1-V2) of each beat was measured. Recordings were of normal sinus rhythm (NSR) (mean of five beats in 8/8 dogs), atrial flutter (AFL) (five beats of one episode), atrial fibrillation (AF) (144 beats in 29 episodes in 7/8), monomorphic ventricular tachycardia (MVT) (24 beats with six morphologies in 2/8), polymorphic ventricular tachycardia (PVT) (63 beats in 15 episodes in 5/8) and premature ventricular contractions (PVC) (29 beats with 29 morphologies in 5/8). Supraventricular rhythms can be differentiated from ventricular rhythms by V1-V2 timing. The mean difference in V1-V2 during AFL and AF vs NSR was 1 ms (range of 0-3 ms). The change from sinus during MVT ranged from 18 to 43 ms (m 31 ms) and during PVC 10 to 75 ms (m 38 ms). Thirty-five of 35 of these ectopic ventricular morphologies exhibited 10 ms or more timing difference compared to corresponding beats of NSR. PVT was consistently distinguished from supraventricular rhythms and MVT by the variability of V1-V2. A-V1 intervals can be used to distinguish supraventricular arrhythmias from sinus rhythm; a 32 ms difference existed for AFL. AF could be detected by the variability in AV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Pacemaker implantation in children: a 21-year experience.

Forty-one children, 20 boys and 21 girls, aged 11 days to 19 years (mean 9.9 years) at initial pacemaker implant, were followed 1 to 248 months (mean 90 months). Ten (mean age 8.2 years) were implanted between 1966 and 1972 (Group I), 14 (mean age 9.9 years) between 1973 and 1980 (Group II) and 17 (mean age 10.9 years) from 1981 through April 1988 (Group III). Arrhythmias were congenital complete heart block in 19, postoperative heart block in 15, acquired heart block in 3, sick sinus syndrome in 3, and bradycardia-induced ventricular fibrillation in 1. Twenty-eight of 41 children had a transvenous implant: 40% of Group I, 71% of Group II and 82% of Group III. Thirteen were cephalic, four subclavian and 11 jugular. Generator site was pectoral in 19, abdominal in 12, intrathoracic in one, and retromammary in nine of 12 girls aged 10 years or more at implant. In Groups I, II and III, 5, 14 and 6 had VOO or VVI units; 5, 0 and 8 dual chamber (VAT, VDD and DDD) pacemakers; 0, 0 and 1 AAI; and 0, 0 and 2 rate-modulated (VVIR) units at initial implant. The average interval between pacer-related hospitalizations in Groups I, II and III was 20, 42, and 39 months. Complications included infection in six, hemothorax in one, and impending pacemaker erosion in one. Six patients died, one of pacer infection, four from primary cardiac disease, and one suddenly without apparent reason. Follow-up continues in 31: 14 are employed full-time, three are homemakers, eight are full-time students, and six are active pre-schoolers.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1986

Male-female responses in various body temperatures during and following exercise in cold air.

During cold exposure women have lower skin temperatures on the trunk and legs. This study evaluated whether these colder temperatures were also manifested in peripheral sites (nose, chin, and finger) where frost bite often occurs. In addition, the core temperature responses to passive rewarming were studied to evaluate whether women experience greater afterdrop as a result of colder shell temperatures. The subjects, eight males (M) and eight females (F), were tested on four occasions, once each at +10, +3.5, -3.5, and -10 degrees C. Each day the subject, clothed in sweat clothes and coveralls, performed 6 bouts of intermittent exercise (20 min. exercise (60W), 10 min. rest) for 3 h in the designated temperature and then rested in +21 degrees C for 1 h. The F had lower Tsk in every test, but finger, nose, and chin temperatures were never lower in F. There were no M-F differences in core temperature during cold exposure or during recovery, even though the Tsk would predict that F had a colder shell. Furthermore, there was no apparent relationship between Tsk rewarming and changes in T core. The data demonstrated no M-F differences in potential for either frost bite or for afterdrop in core temperature.

Adult↗
PubMedDate not supplied

Syncope in childhood.

The records of 108 children, ages 2 to 19 years (mean age 11.3 years), who were referred to the pediatric neurology and pediatric cardiology clinics for syncope, were reviewed. Sixty-six cases were identified retrospectively, and 42 prospectively. Syncope was defined as transient and complete loss of consciousness with no etiology determined at the time of presentation. The mean follow-up was 2.0 years. In 27 cases (25%), an etiology for syncope was found, including migraines in 12 cases (11%), seizures in 9 cases (8%), and cardiac arrhythmias in 6 cases (6%). All other cases were classified as vasovagal (neurocardiogenic). The past medical history, family history, clinical features of each syncopal episode, and diagnostic tests of each subject were correlated to final diagnosis. No clinical or historical features reliably distinguished children with vasovagal syncope from those with other etiologies. Children referred for the evaluation of syncope have a significant incidence of serious but treatable disorders, which should be actively sought.

Adolescent↗