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Biomedical subjects

D Bell

Publications and source records attributed to D Bell.

At least 127 records · Page 7Linked to original sources
PubMed1994

A reproducible method for identification of human genomic DNA autonomously replicating sequences.

We demonstrate a method for the isolation of autonomously replicating sequences from pools of clones obtained from genomic DNA libraries constructed using affinity purification of cruciform DNA. The selection of autonomously replicating sequences was based on their differential ability to replicate as episomes after transfection of pools of plasmid clones into human HeLa cells. Two separate libraries containing affinity-purified cruciform DNA were used, one prepared from DNA of log phase primary human genital fibroblasts and the other prepared from DNA of log phase SW48 colon adenocarcinoma cells. Representative samples of the entire phage libraries were converted to phagemid clones by filamentous helper phage-mediated mass excision to produce pBluescript libraries in Escherichia coli. Clones were grown up individually and the bacteria pooled into groups of 48 for recovery of plasmid DNA. Plasmid pools of 48 independent clones (120 micrograms total) were then transfected by calcium phosphate coprecipitation onto log phase HeLa cells, which were allowed to grow for 3 days before recovery of plasmid by Hirt lysis. The recovery of plasmid from each transfection was estimated to range from 10 to 60 ng. DpnI digestion was then used to digest plasmids which had not been replicated and therefore retained a bacterial methylation pattern which was sensitive to digestion. We estimated from agarose electrophoresis gels that 40-200 pg of recovered plasmid DNA per transfected pool of DNA was resistant to DpnI and therefore was capable of transforming competent E. coli cells. The DpnI-resistant fraction yielded from one to seven independent clones from each pool, with genomic DNA inserts ranging in size from 0.35 to 3.4 kb.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗
PubMed1994

Carotid body tumor associated with hyperparathyroidism.

Hyperparathyroidism in association with carotid body tumor is a rare combination. A common embryologic cellular origin was postulated previously to explain this unusual occurrence. We report a case of left carotid body tumor and left inferior parathyroid adenoma. We believe this to be the sixth reported case in the literature with this combination.

Adenoma↗
PubMed1994

Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man.

1. Oral creatine supplementation has been shown to increase muscle creatine and phosphocreatine concentrations with consequent benefits on performance during short-term maximal exercise. However, recently there have been anecdotal reports that creatine supplementation can also influence the pattern of substrate utilization and improve performance during more prolonged, submaximal exercise, which, based on recent experimental evidence, may have some scientific justification. 2. Eight men performed a continuous incremental exercise test running at 10 km/h on a motorized treadmill at predetermined workloads from 50% to 90% of maximal oxygen uptake, before and after 5 days of creatine supplementation (4 x 5 g daily). Exercise was performed for 6 min at each workload to achieve a steady state, and respiratory gas exchange and blood lactate concentrations were measured during the last 30 s at each workload. Measurements were also made at 5-min intervals for the first 15 min of recovery. 3. The results showed no measurable effect of creatine supplementation on respiratory gas exchange and blood lactate concentrations during either incremental submaximal exercise or recovery. This suggests that creatine supplementation does not influence substrate utilization during and after this type of exercise.

Adult↗
PubMed1994

Delayed presentation: dislocation of the proximal tibiofibular joint after knee dislocation.

Attention is brought to a unique case of an anterior dislocation of the proximal tibiofibular joint detected 1 month following closed reduction of a posterior knee dislocation. Open reduction and internal fixation were necessary to achieve a stable proximal tibiofibular joint. Additional attention should be paid to the proximal tibiofibular joint when evaluating acute or chronic knee dislocation.

Accidents, Traffic↗
PubMed1994

Secretin and vasoactive intestinal peptide are potent stimulants of cellular contraction and accumulation of cyclic AMP in rat ventricular cardiomyocytes.

Although secretin and vasoactive intestinal peptide (VIP) stimulate production of the second-messenger substance cyclic AMP and exert a positive inotropic action on rat ventricle in vitro, a direct action of these peptides on cardiomyocytes has not been established. In contrast to hearts of other mammalian species, which possess VIP-preferring receptors, rat heart is unique in that the existence of a "relatively nonselective receptor" at which both secretin and VIP may bind has been proposed. We wished to define the receptor(s) for secretin and VIP present on rat ventricular cardiomyocytes using a homogeneous suspension of viable cells. With adenosine deaminase 5 U/ml and the phosphodiesterase (PDE) inhibitor isobutyl methylxanthine (IBMX) 1 mM, both secretin and VIP increased intracellular levels of cyclic AMP maximally and concentration dependently after 5 min: EC50 values were 8 and 58 nM, respectively. At maximally effective concentrations, secretin 1 microM increased intracellular levels of cyclic AMP fourfold above basal levels, whereas a 1.6-fold increase was induced by VIP 10 microM. Maximum changes in cell length (dL) of isolated cardiomyocytes during electrically stimulated (0.5 Hz) contractions were determined in the presence of adenosine deaminase 2.5 U/ml. Under these conditions, both secretin and VIP produced a concentration-dependent positive contractile response that became maximal 5 min after addition of the peptide. Secretin 50 nM increased the amplitude of cellular contractions maximally to a value 37% greater than that obtained without peptide. VIP 20 nM increased the amplitude of cellular contractions maximally to a value 19% greater than that obtained without peptide. The EC50 values were 470 and 700 pM for VIP and secretin, respectively. The selective antagonist at VIP-preferring receptors, 4-Cl DPhe-6 Leu-17 VIP 10 microM did not antagonise the actions of VIP. In the presence of the selective antagonist at receptors for secretin, secretin 7-27 > or = 10 microM, the concentration dependence of the effect of secretin on accumulation of cellular cyclic AMP and contractile amplitude displayed a rightward parallel shift: the pA2 value for secretin 7-27 was 4.96. Secretin 7-27 also induced a rightward parallel shift of the concentration dependence of the actions of VIP. VIP 10 microM was additive with low concentrations of secretin (< 10 nM) in stimulating production of cyclic AMP but antagonised this response at higher concentrations of secretin (> 10 nM). Similarly, VIP 2 and 20 nM enhanced the contractile response to low concentrations of secretin (< 1 nM), but antagonised the response at higher concentrations of secretin (> 1 nM).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Calcitonin gene-related peptide stimulates a positive contractile response in rat ventricular cardiomyocytes.

Calcitonin gene-related peptide (CGRP) elicits marked positive inotropic and chronotropic actions in the atria of several mammals. The second-messenger substance cyclic AMP and activation of L-type calcium channels have been implicated in these actions, but CGRP failed consistently to stimulate a contractile response in ventricular tissue obtained from various mammals. We assessed the actions of CGRP using isolated ventricular cardiomyocytes obtained from adult rats. Maximum changes in cell length (dL) of isolated cardiomyocytes during electrically stimulated (0.5 Hz) contractions were determined with adenosine deaminase (2.5 U/ml). In these conditions, CGRP produced a potent concentration-dependent positive contractile response that became maximal 4 min after initial stimulation. CGRP increased amplitude of cellular contractions maximally at a 1-nM concentration to a value 21.4% greater than that obtained without peptide. The EC50 value for the response was 31 pM. At concentrations greater than 1 nM, amplitude of the cellular contractile response decreased rapidly. The CGRP2-selective agonist, [cys ACM2,7] CGRP, increased the amplitude of cellular contractions maximally at 500 nM to a value 19.8% greater than that obtained without peptide. EC50 for this response was 6 nM. Salmon calcitonin (< or = 100 nM) did not elicit a significant contractile response. The fragment, CGRP8-37, a selective antagonist at the CGRP1 receptor subtype, while devoid of agonist activity, was a potent competitive antagonist of the positive contractile action of CGRP (pA2 value = 7.95). CGRP, present at maximally effective concentration (1 nM), when combined with isoprenaline ISO 100 pM-1 microM, elicited a greater increase in contractile amplitude than that elicited by ISO 100 pM-1 microM without CGRP. CGRP 1 nM combined with low concentrations of extracellular calcium ion < or = 4 mM produced a greater increase in contractile amplitude than that elicited by calcium ion < or = 4 mM without CGRP, but this additive effect was abolished in the presence of higher concentrations of extracellular calcium ion (> 4 mM). The cyclic AMP antagonist, Rp-cyclic AMPS (< or = 200 microM), did not inhibit the contractile response to CGRP 1 nM, but inhibited the contractile responses to ISO 100 nM and secretin 20 nM significantly and in a concentration-dependent manner. Diltiazem < or = 1 microM, a selective antagonist of L-type calcium channels, also failed to inhibit the contractile response to CGRP 1 nM but inhibited the contractile responses to ISO 100 nM and secretin 20 nM significantly and in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

An evaluation of drug injection behaviors and HIV infection. National AIDS Research Consortium.

This paper investigates domains of drug injection behavior and the association of derived factors to HIV serostatus. Two sets of data were randomly selected and matched from a national data set of over 40,000 drug injectors. One set was HIV seropositive and the other HIV seronegative heterosexual injectors. Samples were matched to control for the effects of race/ethnicity, gender, and age on serostatus. Factor analysis was used to investigate relationships among drug injection behaviors. Four independent factors were found. Two factors were found to be statistically related to HIV serostatus in high seroprevalence areas. None of the needle use factors was found to be significantly associated with serostatus in low seroprevalence areas.

Adult↗
PubMed1994

The value of serum C-reactive protein levels as a marker of sepsis in intensive care unit patients.

A one-year prospective study was carried out to assess the value of routine serum C-reactive protein (CRP) measurement in the early diagnosis of infection in ICU patients of a District General Hospital. Ninety-one patients were included in the study. Sixty-eight patients yielded 28 proved and 77 suspected episodes of infection. Control data were drawn from 23 uninfected ICU patients. Both absolute values and percentage rates of change were examined for the following variables: serum CRP, maximum daily temperature and peripheral white blood cell count. Neither absolute CRP levels nor rates of change in CRP were found to relate significantly to proved infection. In the group in whom infection was suspected but not proved, absolute CRP levels were higher than controls on the day before the suspected infection (p = 0.019), but were not significantly raised on the day of infection nor the day after. The only significant rises in CRP (> 25%) were found in the suspected infection group from the day before to the day of infection, when compared with controls (p = 0.04). Traditional markers of infection--maximum temperature and peripheral white blood cell count--were significantly associated with infection. Maximum temperature was significantly higher in both proved and suspected infection on the day before infection (p = 0.000 and 0.001), and on the day of infection (p = 0.025 and 0.03), compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1994

Quality of life at three months following admission to intensive and coronary care units.

OBJECTIVE: Measurement of quality of life three months following critical illness, to assess impact on health expectations. DESIGN: Continuous quantitative study of patients admitted to a combined intensive and coronary care unit during a nine-month period. Questionnaires giving baseline information were completed soon after admission, and postal questionnaires incorporating the Nottingham Health Profile were sent to surviving patients three months following discharge from the unit. SETTING: District General Hospital. SUBJECTS: ICU sample included 60 patients, male n = 31, female n = 29. Twenty-nine patients received surgical treatment, 31 patients received medical treatment. Coronary Care Unit (CCU) sample included 112 patients, male n = 74, female n = 38. Fifty-four patients admitted following acute myocardial infarction (MI), 58 patients non-MI admission. MEASUREMENTS AND MAIN RESULTS: Hospital mortality for ICU patients was 31%, increasing to 34% at three months. Hospital mortality for CCU patients was 14%, increasing to 19% at three months. Significant differences in mean NHP scores between ICU and CCU patients were noted with higher CCU scores in the areas of sleep (p = 0.04), and social isolation (p = 0.01). Within the ICU group surgical patients had a higher mean NHP score in the area of pain (p = 0.02). There were no significant differences in the scores of male and female ICU patients. Within the CCU group non-MI patients had significantly higher mean scores than MI patients in the areas of energy (p = 0.007), pain (p = 0.04), emotion (p = 0.05), social isolation (p = 0.01) and physical ability (p = 0.003). Female CCU patients had higher mean NHP scores than male patients with significant differences in the areas of pain (p = 0.04), sleep (p = 0.009) and physical ability (p = 0.006). CONCLUSION: ICU patient quality of life three months after admission compares favourably with a corresponding group of CCU patients, particularly in areas of sleep and social isolation. CCU patients' general functional status deteriorated significantly compared to their pre-admission status. Critical illness is a costly area of medicine, but the results suggest that outcomes are beneficial in terms of quality of life for those surviving acute illness.

Activities of Daily Living↗
PubMed1994

A phase II study of carboplatin and cisplatin in advanced ovarian cancer.

In view of the single agent activity of both cisplatin and carboplatin in epithelial ovarian cancer, and their different toxicity profiles, we carried out a phase II study of low dose cisplatin (50 mg/m2) in combination with moderate dose carboplatin (300 mg/m2) in patients with advanced ovarian cancer. Fourteen patients, all of whom had bulky disease and over half of whom had Stage IV disease, were eligible for assessment of response and toxicity. An overall response rate of 71% was demonstrated (57% complete response, 14% partial response), which is at least equivalent to other regimens used in first line treatment of ovarian cancer. Toxicities encountered were nausea/vomiting and myelosuppression, however no serious renal neuro or ototoxicity was observed and the regimen does not cause significant alopecia. This combination may be a practical alternative to regimens which use high dose cisplatin to achieve similar efficacy.

Aged↗
PubMed1993

Structural determinants of quaternary ammonium blockers for batrachotoxin-modified Na+ channels.

Amphipathic quaternary ammonium (QA) compounds are potent blockers of batrachotoxin (BTX)-modified Na+ channels incorporated into planar lipid bilayers. To examine the topology of the QA binding site, we selected two series of QA compounds as structural probes. One series contains two separate hydrophobic moieties but with a common hydrophilic dimethyl QA ion. Most of the QAs within this group bind to BTX-modified Na+ channels with relatively high affinities. For example, benzyldimethyldodecyl ammonium ions, when applied internally, block single, muscle, BTX-modified Na+ channels in bilayers with a one-to-one relationship and display an equilibrium dissociation constant (Kd) of 0.2 microM at +50 mV. Furthermore, the QA dwell times appear to correlate with QA hydrophobic interactions with the channel. These results indicate that there are two large hydrophobic binding domains within the QA binding site. The QAs in the second series contain a hydrophilic head group (trialkylammonium) of variable size but with a common dodecyl hydrophobic tail. Tripropyldodecyl QAs block BTX-modified Na+ channels more effectively (Kd = 0.4 microM at +50 mV) than do trimethyl- and triethyldodecyl QAs, suggesting that the internal Na+ permeation pathway is at least 9 A wide. However, tributyl- and tripentyldodecyl QAs show much lower affinities for BTX-modified Na+ channels at comparable concentrations. These drugs are cut off from binding, probably as a result of the size of their hydrophilic heads (> 10 A), which may be too large to fit in the QA binding site and too bulky to travel freely within the internal permeation pathway. Under whole-cell voltage-clamp conditions, we have further found that BTX-modified Na+ currents in clonal GH3 cells can be blocked by these two series of QA ions, albeit only when the activation gate is open. Closed channels at rest do not bind appreciably with these QA ions. Binding of QA ions is reduced by external Na+ ions in GH3 cells in a manner indicating that external Na+ ions can clear the bound QA ions from the Na+ pore. These results from GH3 cells mirror those obtained with QA blockers in K+ channels of squid axons and suggest that the QA binding domains in BTX-modified Na+ channels and K+ channels may be structurally conserved.

Animals↗
PubMed1993

Arthritis in hemochromatosis.

We reviewed the clinical and radiographic features of arthropathy in 25 subjects with hemochromatosis, 16 probands and 9 discovered homozygous relatives. Clinical arthritis was present in 15/16 probands and 1/9 discovered homozygotes (p < 0.005). Radiologic evidence of arthropathy was seen additionally in 2 asymptomatic discovered homozygotes. The metacarpophalangeal joints and wrists were most commonly involved; severe hip disease occurred in 6. Patients with clinical or radiologic arthropathy were older than patients without. Arthropathy occurred in all 4 female probands, but in none of the 3 female discovered homozygotes. Chondrocalcinosis was seen in 9 subjects but was usually asymptomatic. The arthritis of hemochromatosis may be difficult to differentiate from several other joint diseases, especially calcium pyrophosphate dihydrate deposition disease.

Adult↗
PubMed1992

A calcium model with random absorption: a stochastic approach.

Absorption of calcium, or any mineral, by the body is subject to the random fluctuations typical of diffusion through membranes. In this paper we consider the absorption of calcium from the gut as a white noise process added to the deterministic model of Sen & Mohr (1990, J. theor. Biol. 142, 179-188). The first two moments for the amount of calcium in the extracellular fluid (ECF) have been derived using the Ito Calculus. A confidence interval for the total amount of calcium in the ECF is constructed. The equations for the first two moments of the fraction of dose calcium in the ECF are also given. Suggestions are made for the collection of experimental data in a form which should be helpful in investigating the magnitude of the stochastic effect.

Calcium↗