Search PubMed⌕ Search

Biomedical subjects

D Roberts

Publications and source records attributed to D Roberts.

At least 217 records · Page 12Linked to original sources

Evidence for age-associated reduction in acetylcholine release and smooth muscle response in the rat colon.

The effect of aging was examined on cholinergically mediated contractions and acetylcholine (ACh) release in isolated colonic segments from Fischer (F344 x BN) F1 rats, 4-8 mo (postpubertal) and 22-28 mo (senescent) of age. This species demonstrates age-dependent slowing of colonic transit. Muscle tension response to electrical stimulation of cholinergic neural pathways and application of ACh was significantly decreased in preparations from senescent compared with postpubertal animals. We focused on the hypothesis that aging was associated with reduced ACh release that resulted from decreased calcium influx through membrane calcium channels. Aging did not affect either the synthesis of [3H]ACh from [3H]choline or the percentage of 3H released in the form of [3H]ACh. However, elevated KCl-evoked release of [3H]ACh was significantly reduced in tissue from senescent compared with postpubertal animals. Treatment with the calcium ionophore ionomycin increased [3H]ACh release in tissue from senescent animals to near postpubertal levels. However, increasing extracellular calcium concentration ([Ca2+]o) from 1.2 to 5 mM did not increase the amount of transmitter release in tissue from senescent animals to the levels observed with 1.2 mM [Ca2+]o in postpubertal tissue. The neuronal calcium channel antagonist omega-conotoxin GVIA inhibited acetylcholine release in a concentration-dependent manner with half-maximal inhibitory values of 1.8 and 8.2 nM for senescent and postpubertal preparations, respectively. In summary, age-dependent reduction in ACh release was observed in the rat colon myenteric plexus that may, in part, be associated with decreased calcium influx via membrane calcium channels.

Acetylcholine↗

The effect of prolonged perfusion with a membrane oxygenator (PPMO) on white blood cells.

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% +/- 9, 72% +/- 2 and 76% +/- 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 +/- 1.5, 32.6 +/- 2.2 and 40.3 +/- 8.3 x 10(2)%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 +/- 1.5, 9.7 +/- 1.2 and 13.9 +/- 2.1 x 10(6)/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% +/- 0.3, 23% +/- 0.2 and 14% +/- 0.1 and 14% +/- 0.1 at 24, 48 and 72 hours respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation↗

Is the prescription of amphetamine justified as a harm reduction measure?

Although amphetamine is the most widely illicitly used drug in the United Kingdom after cannabis, relatively few problematic users present to treatment agencies. Injecting amphetamine users are a high risk group as far as HIV transmission is concerned. This paper reviews the first 3 years' operation of an oral amphetamine prescribing programme for injecting users. Over half the subjects ceased injecting, and there was a considerable reduction in injecting by the remainder. 85% had not used or shared injecting equipment during the programme. However, subjects reported still using street amphetamine and offending, although at a lower rate than previously. There was little change in sexual practices. There was an increase in primary amphetamine users presenting for treatment. There is a case to be made that closely controlled and monitored programmes such as this can be justified on harm reduction grounds. A number of issues concerned with amphetamine prescribing are discussed.

Administration, Oral↗

Antiemetic prophylaxis for strabismus surgery.

Droperidol can reduce the high incidence of vomiting after pediatric strabismus surgery; however, its use may be associated with sedation, delayed hospital discharge, dysphoria and extrapyramidal signs. Midazolam, a short-acting benzodiazepine with antiemetic properties, has few side effects and may be a suitable alternative. We prospectively compared the antiemetic effect of these two drugs in 393 healthy children aged 18 months to 14 years undergoing outpatient strabismus surgery. The children were randomly assigned to receive midazolam hydrochloride (50 micrograms/kg) (199 patients) or droperidol (50 micrograms/kg) (194 children). The incidence rates of vomiting in the two groups were 45% and 37% respectively, a nonsignificant difference. The incidence of vomiting was not affected by the duration of anesthesia, but the number of muscles repaired was a significant predictor of postoperative vomiting (p < 0.001).

Adolescent↗

Measurement of myosin light chain I and troponin T as markers of myocardial damage after cardiac surgery.

The purpose of the study was to test cardiac myosin light chain I (CMLCI) and troponin T (TNT) as markers on myocardial damage after heart surgery. Forty-three patients undergoing cardiac surgery were arbitrarily divided into two groups according to creatine kinase MB isoenzyme (CK-MB) levels and postoperative electrocardiogram (ECG) changes. Group 1: CK-MB > 100 micrograms/L or ECG changes (extensive myocardial damage, 42%); Group 2: CK-MB < 100 micrograms/L and no ECG changes (minimal myocardial damage, 58%). Group 1 was divided into 2 groups (Infarction and Injury groups). CMLCI levels showed strong correlations with TNT levels after the operation. The peak CMLCI and TNT levels in group 1 were significantly higher than in group 2. The peak CMLCI in the Infarction group was significantly higher than in the Injury group. TNT showed different patterns in the Infarction and Injury groups. This study showed that CMLCI and TNT estimation could evaluate myocardial damage over several postoperative days. TNT estimation could identify myocardial damage earlier than CMLCI, however CMLCI could discriminate perioperative infarction better than TNT.

Aged↗

Mixed germ cell malignancy of the ovary concurrent with pregnancy.

BACKGROUND: A rare malignant germ cell tumor of the ovary during pregnancy was detected by screening of maternal serum alpha-fetoprotein (MSAFP). Treatment of this uncommon tumor during pregnancy incorporated combination chemotherapy including etoposide. CASE: An 18-year-old primiparous woman undergoing antenatal genetic screening was found to have an extremely elevated MSAFP of 477.8 IU/mL, or 12.46 multiples of the median. Oophorectomy and staging laparotomy at 20.5 weeks' gestation resulted in the diagnosis of mixed germ cell tumor of the ovary, with both endodermal sinus tumor and grade 3 immature teratoma. The patient received three courses of cis-platinum, etoposide, and bleomycin. Maternal serum AFP titers had returned to normal pregnancy levels by the start of the second course. A healthy female infant was delivered at 39 weeks' gestation following induction of labor for pregnancy-induced hypertension. CONCLUSION: Elevated MSAFP levels may be a presenting sign of malignant ovarian germ cell neoplasms. This report describes both surgical and chemotherapeutic treatment of a germ cell malignancy during pregnancy, with delivery at term. To date, major fetal toxicity from chemotherapy has not been identified.

Adolescent↗

Antibody as a surrogate receptor in the screening of a phage display library.

Polyclonal antibody (Ab) against biotin (anti-biotin Ab) was evaluated as a source of shape mimics for the biotin-binding pocket of streptavidin (Sv). A 6-mer phage display library was panned with anti-biotin and the selected peptide sequences compared to those obtained by panning directly with Sv. The consensus XXYYLH was identified with the anti-biotin Ab probe, while GDWVFI and PWPWLG were the major motifs identified by Sv panning. Although some similarities were observed between sequences of the products from both pannings, only phage displaying the GDWVFI and PWPWLG peptides demonstrated biotin-sensitive Sv binding in ELISA and micropanning assays. Phage displaying GDWVFI could be eluted from Sv with either acid or biotin, but not phosphate-buffered saline (PBS), whereas phage displaying PWPWLG eluted with acid, biotin and PBS.

Amino Acid Sequence↗

DSS4-1 is a dominant suppressor of sec4-8 that encodes a nucleotide exchange protein that aids Sec4p function.

The protein Sec4p plays an essential role at the final stage of the yeast secretory pathway and belongs to the ras superfamily of GTP-binding proteins, more specifically to a branch that includes Ypt1p in Saccharomyces cerevisiae and rab proteins in mammalian cells. GTP-binding proteins change conformation depending on whether GTP or GDP is bound and can thus act as a regulatory switch. The protein remains in its inactive, GDP-bound form until exchange of GTP for GDP allows it to stimulate a downstream effector. This interaction is curtailed by GTP hydrolysis. The rates of nucleotide exchange and GTP hydrolysis can be regulated by interaction with accessory proteins. Although GDP dissociation stimulators (GDS) have been identified that act on members of the ras and rho branches of the superfamily, less is known regarding GDSs that act on members of the Sec4/Ypt1/Rab subgroup. A preliminary characterization of a Rab3A GDP dissociation stimulating activity has been presented. We report here the use of suppressor analysis to clone a gene, dss4, encoding a 17K protein that aids Sec4p action in vivo by functioning as a GDP dissociation stimulator.

Amino Acid Sequence↗

A mammalian guanine-nucleotide-releasing protein enhances function of yeast secretory protein Sec4.

Small GTP-binding proteins of the ras superfamily are important for exocytosis from eukaryotic cells. GTP-binding proteins can exist in two different conformations depending on whether they are bound to GDP or GTP, and are thought to function as molecular switches that regulate a variety of cellular processes. The GTP-GDP cycle is controlled by accessory proteins that promote the exchange of bound GDP or the hydrolysis of GTP. The protein Sec4, a member of the Sec4/Ypt1/Rab branch of the Ras superfamily, is involved in a late stage of the secretory pathway in yeast. Here we report the isolation of a mammalian complementary DNA, mss4, encoding a GDP-releasing protein that enhances Sec4 function. The Mss4 protein also stimulates GDP release from Ypt1 and from the mammalian protein Rab3a, but not from Ras2. Mss4 shows sequence similarity to Dss4, a yeast protein with similar biochemical properties.

ATP-Binding Cassette Transporters↗

Staphylococcal food poisoning in the United Kingdom, 1969-90.

Between 1969 and 1990 strains of Staphylococcus aureus from 359 outbreaks and sporadic cases of staphylococcal food poisoning in the United Kingdom were examined in the PHLS Food Hygiene Laboratory for the production of enterotoxin. In a number of instances the incriminated foods were also examined for the presence of enterotoxin. Strains from 79% of incidents produced enterotoxin A alone or together with another enterotoxin. The level of S. aureus present in the foods ranged from no viable S. aureus detected to 1.5 x 10(10) c.f.u./g with a median of 3.0 x 10(7) c.f.u./g. Enterotoxin was detected in foods in the absence of viable S. aureus in only two outbreaks and in both cheese was the implicated food. Meat, poultry or their products were the vehicle in 75% of incidents with ham and chicken most frequently implicated. Other foods included fish and shellfish (7%) and milk and milk products (8%). Most contamination took place in the home followed by restaurants and shops. Seventy-one percent of the incident strains were lysed by phages of group III or I/III.

Bacterial Toxins↗