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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 307 records · Page 17Linked to original sources
PubMed1993

Patterns of smoking during pregnancy in Canterbury.

AIMS: To examine the prevalence and patterns of smoking in pregnancy with the object of improving smokefree programmes in the region. METHODS: A postal questionnaire on smoking in pregnancy was sent to all 1916 mothers giving singleton births in the Canterbury region over a five month period. There was a 71.7% response rate, however, smokers were significantly under represented. Data from nonresponders was obtained from obstetric records. RESULTS: Of the total sample, 30% smoked during their last pregnancy. There were significant differences between responders and nonresponders. The responders contained only 60% of all smokers. Nonresponders had twice the incidence of smoking, were more likely to identify as Maori, were younger and had lower birth weights. Nonresponders contained 40% of all smokers. Of the responders, 333 mothers smoked during at least some part of pregnancy: 113 (34%) quit, 168 (50%) cut down, and 48 (15%) made no change. Most (90%) of those who did quit did so during the first trimester. Lighter smokers (less than 10 per day) were more likely to quit or cut down. But smoking rates subsequently increased after the birth. CONCLUSIONS: In Canterbury, 30% of pregnant women smoke. Although 64% indicated a wish to quit and 30% to cut down, this contrasted with what they actually achieved: 34% quit and 50% cut down. Pregnancy influences smoking patterns and is an opportune time for smokefree promotion.

Adult↗
PubMed1993

Dror, a potential neurotrophic receptor gene, encodes a Drosophila homolog of the vertebrate Ror family of Trk-related receptor tyrosine kinases.

We have identified a Drosophila gene, Dror, which encodes a putative receptor tyrosine kinase (RTK) and maps to cytological location 31B/C on the second chromosome. In embryos, this gene is expressed specifically in the developing nervous system. The Dror protein appears to be a homolog of two human RTKs, Ror1 and Ror2. Dror and Ror1 proteins share 36% amino acid identity in their extracellular domains and 61% identity in their catalytic tyrosine kinase (TK) domains. Ror1 and Ror2 were originally identified on the basis of the similarity of their TK domains to the TK domains of members of the Trk family of neurotrophin receptors. The Dror protein shows even greater similarity to the Trk proteins within this region than do the human Ror proteins. In light of its similarity to trk and its neural-specific expression pattern, we suggest that Dror may encode a neurotrophic receptor that functions during early stages of neural development in Drosophila.

Amino Acid Sequence↗
PubMed1993

Human T-cell leukemia virus type II infection frequently goes undetected in contemporary US blood donors.

Serologic screening for human T-cell leukemia virus type I (HTLV-I) infection was begun in US blood banks with the licensure of enzyme-linked immunosorbent assays (ELISA) in December 1988. We examined the donation histories of the first 60 Western blot (WB)-confirmed HTLV-I/II positive donors to one blood center and found 8 had made 16 previous donations that scored negative on the screening ELISA. All 16 donations had ELISA absorbance below the cutoff for a positive assay, but still well above that of the average donation (17.6% +/- 5.7% of the cutoff). In a more extensive study, 17 donations from a total of 61,752 at six blood centers were both ELISA-positive and WB-positive for HTLV-I (4) or HTLV-II (13), and 218 samples had ELISA absorbance greater than 50% of the ELISA cutoff. One hundred seventy-eight of the 218 were tested further by WB and 11 were found positive. All 11 positives were confirmed by polymerase chain reaction; 10 had HTLV-II and 1 had HTLV-I. Thus, the HTLV-I-based screening ELISA missed at least 10 of 23, or 43% (95% confidence interval, 23% to 66%), of HTLV-II infections, compared with 1 of 5, or 20%, of HTLV-I infections.

Blood Donors↗
PubMed1993

Modeling side-chain conformation for homologous proteins using an energy-based rotamer search.

We have developed a computational method for accurately predicting the conformation of side-chain atoms when building a protein structure from a known homologous structure. A library of rotamers is used to model the side-chains, allowing an average of five to six different conformations per residue. Local sites of adjacent side-chains are defined throughout the protein, and all combinations of side-chain rotamers are evaluated within each site using a molecular mechanics force field enhanced by the inclusion of a solvation term. At each site, the lowest energy combination of side-chains is identified and added onto the fixed protein backbone. A series of test cases using the refined X-ray structure of alpha-lytic protease has shown that: (1) the force field can correctly predict up to 90% of side-chain rotamers; (2) the assumption of side-chain rotamer geometry is usually a very good approximation; and (3) the complete combinatorial conformation search is able overcome local minima and identify the lowest energy rotamer set for the protein in the absence of a starting bias to the correct structure. Tests with several pairs of homologous proteins have shown that the algorithm is quite successful at predicting side-chain conformation even when the protein backbone used to generate side-chain positions deviates from the correct conformation. The root-mean-square (r.m.s.) deviation of predicted side-chain atoms rises from 1.31 A (average r.m.s.d. 0.73 A) in a test case with the correct backbone to only 2.68 A (1.95 A average r.m.s.d.) in a test case with < 35% homology. The high accuracy of this method suggests that it may be a useful automated tool for modeling protein structure.

Algorithms↗
PubMed1993

Isolation and characterization of a tobacco cDNA clone encoding a putative MAP kinase.

We have isolated and sequenced a MAP (mitogen-activated protein) kinase-type cDNA from a tobacco (Nicotiana tabacum L.) cell suspension cDNA library by screening with a PCR fragment amplified from the same library with oligonucleotide primers corresponding to two sequences conserved in yeast and animal MAP kinases. The tobacco sequence, ntf3, shows 45-54% identity to various members of the MAP kinase family at the protein level. Northern experiments showed that ntf3 is expressed in all tobacco tissues tested, including pollen isolated at different developmental stages. Southern analysis indicated that, as in other organisms, there is a family of MAP kinase genes in tobacco. In complementary tests, ntf3 could not substitute the yeast MAP kinase genes fus3 and kss1.

Amino Acid Sequence↗
PubMed1993

Purification and characterization of tripeptidylpeptidase-II from post-mortem human brain.

A soluble tripeptidylaminopeptidase has been isolated from human post-mortem cerebral cortex by anion exchange, hydrophobic interaction and size-exclusion chromatography. From gel filtration studies the active enzyme can exist in both high molecular weight (M(r) > 10(6) and smaller forms. The enzyme hydrolyses Ala-Ala-Phe-7-amido-4-methylcoumarin with a pH optimum of around 7.5 and Km of 148 microM. It did not hydrolyse N-succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin, aminoacyl- or dipeptidyl-7-amido-methylcoumarins and was not inhibited by bestatin. The enzyme was inhibited by phenylmethylsulphonyl-fluoride, 3,4-dichloroisocoumarin, N-hydroxymercuriphenyl-sulphonic acid and N-ethylmaleimide showing that its activity is serine and cysteine dependent. The purified enzyme released tripeptides from several naturally occurring neuropeptides with quite broad specificity. Cholecystokinin octapeptide, angiotensin III and neurokinin A were the most rapidly hydrolysed. Peptides with Pro residues around the point of cleavage were not hydrolysed.

Amino Acid Sequence↗
PubMed1993

Arrhythmogenic doses of epinephrine are similar during desflurane or isoflurane anesthesia in humans.

BACKGROUND: Inhaled anesthetics can alter the arrhythmogenicity of exogenously administered epinephrine. Although swine anesthetized with desflurane or isoflurane do not differ in their arrhythmic response to exogenous epinephrine, the relative effect of epinephrine in the presence of these anesthetics in humans is untested. METHODS: The authors compared the arrhythmogenicity of submucosally administered epinephrine in 36 ASA physical status 1 and 2 patients undergoing transsphenoidal resection of pituitary tumors who were randomly assigned to receive 1.0-1.3 MAC desflurane or isoflurane anesthesia. A surgeon, blinded to the administered anesthetic and the concentration of epinephrine, injected 1:50,000, 1:75,000, or 1:100,000 (20, 13.3, or 10 micrograms/ml) epinephrine in saline of volumes sufficient for surgical need. The authors defined a positive response as three or more premature ventricular contractions (PVCs) in the 5 min after starting the injection. RESULTS: No patient given either anesthetic developed any PVCs with epinephrine doses less than 7.0 micrograms/kg. Greater doses of epinephrine (7.0-13.0 micrograms/kg) produced positive responses at equal frequencies in the two anesthetic groups. CONCLUSIONS: The authors concluded that isoflurane and desflurane do not differ in their sensitization of human myocardium to the arrhythmogenic effects of exogenously administered epinephrine.

Adolescent↗
PubMed1993

Mouse skin is particularly susceptible to tumor initiation during early anagen of the hair cycle: possible involvement of hair follicle stem cells.

Stem cells are believed to be a necessary target of chemical carcinogens. Based on autoradiographic, ultrastructural, and biologic criteria, we have recently proposed that hair follicle stem cells reside not in the bulb, but in the upper outer root sheath in an area called the bulge. Proliferating cells have been shown to be more susceptible to tumor initiation, and we have recently demonstrated that cells in the bulge undergo transient proliferation during early anagen. Therefore, we theorized that mouse skin should be particularly susceptible to carcinogen application during early anagen phase. In this paper, we show that early anagen Swiss and Sencar mouse skin is indeed particularly susceptible to one- and two-stage chemical carcinogenesis, resulting in tumor yields one to five times those obtained with telogen-timed carcinogen application. Our findings implicate a possible involvement of the bulge cells as precursors to some of the skin cancers, and support the concept that these are stem cells. These observations also raise important questions about the cellular origins and biologic behavior of chemically induced murine skin tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Plasma cell populations in labial salivary glands from patients with and without Sjögren's syndrome.

Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (n = 25) and compared with glands from patients with a variety of systemic diseases (n = 32) and normal individuals (n = 15). Based on qualitative and quantitative analysis, glands from the systemic disease group were divided into normal histology (n = 24) and non-specific inflammation (n = 8) groups. There were no significant differences in cell densities or Ig class proportions between histologically normal glands from patients and those from normal volunteers. Total immunocyte densities were significantly increased in sialadenitis (P < 0.025) and Sjögren's syndrome (P < 0.001) compared with normal histology glands. In both the sialadenitis and Sjögren's syndrome groups there were significant increases in IgG and IgM cell densities (IgG, P < 0.006; IgM, P < 0.001) and proportions (IgG, P < 0.05; IgM, P < 0.001). There were no significant differences in immunocyte densities or proportions between the sialadenitis and Sjögren's syndrome groups except for a lower percentage proportion of IgA cells in the latter (P < 0.038). In all groups the total and individual Ig-class cell densities showed significant positive correlations with extent of leucocyte infiltration (P < 0.01) and negative correlations between IgA and IgG and/or IgM cell proportions. Analysis of the plasma cell data alone and in combination with quantifiable histological parameters failed to yield specific or sensitive diagnostic information. The results suggest that changes in glandular plasma cell populations in Sjögren's syndrome are non-specific.

Adult↗
PubMed1993

Evaluation of ICI D7114, a putative stimulant of brown adipocytes, on histamine-contracted guinea-pig ileum.

1. Experiments were performed to characterize the effects of the novel brown adipocyte stimulant, ICI D7114, in the guinea-pig isolated ileum, right atrium and tracheal chain. In the ileum, agonist-induced inhibition of the contractile response to either histamine or prostaglandin E2 (PGE2) was assessed, along with effects on resting rate in the atrium and resting tone in the tracheal chain. In the latter two preparations, antagonism of isoprenaline-induced responses by ICI D7114 was also assessed. 2. Inhibitory responses were obtained in the ileum to ICI D7114, isoprenaline, BRL37344, and noradrenaline. The responses to ICI D7114, isoprenaline and BRL37344 were resistant to blockade with propranolol (5 microM), naloxone (1 microM), methysergide (0.1 microM), cimetidine, indomethacin and 8-phenyltheophylline (all 10 microM). These responses to isoprenaline, in the presence of propranolol (5 microM), were competitively antagonized by alprenolol (1-100 microM) with a pA2 value of 6.44. The responses to ICI D7114 and BRL37344 were antagonized by single concentrations of alprenolol (1 microM) with apparent pKB values of 6.53 and 6.57 respectively. These data indicate an effect of ICI D7114 at the atypical beta-adrenoceptor in the guinea-pig ileum. 3. The order and relative potency of agonists at the atypical beta-adrenoceptor was BRL37344 (4) < isoprenaline (1) = ICI D7114 (1.1) > noradrenaline (0.5). 4. ICI D7114 (1 nM - 10 microM) caused no significant change in the rate of beating or the resting tone of the guinea-pig right atrium or tracheal chain respectively. It did, however, cause selective blockade of the responses to isoprenaline in these tissues (apparent pKB values 7.63 and 5.85 in atrium and tracheal chain respectively). Responses to histamine (atrium) and aminophylline (tracheal chain) were not significantly affected by 10 microM ICI D7114.5. These results demonstrate that ICI D7114 possesses selective agonist activity at atypical beta-adrenoceptors in the guinea-pig ileum and its use as a tool may help to establish a role for the atypical beta-adrenoceptor in the control of gastrointestinal motility.

Adipose Tissue, Brown↗
PubMed1993

Zeneca ZD7114 acts as an antagonist at beta 3-adrenoceptors in rat isolated ileum.

1. The relaxant effects of Zeneca ZD7114, BRL37344 (putative beta 3-adrenoceptor agonists) and various phenylethylamine-based agonists were studied in isolated ileum of the rat where tone was increased with carbachol (0.5 microM). Agonist-induced relaxation.was measured under equilibrium conditions with alpha-, beta 1- and beta 2-adrenoceptors inhibited. 2. Relaxant responses were obtained to isoprenaline, noradrenaline, and BRL37344, although, the efficacy of this latter agent was significantly.lower than that of isoprenaline. Salbutamol caused weak relaxation (< 20%) at high concentrations (10 microM) and ZD7114 was without significant relaxant effect even at high concentrations (10 microM). 3. Relaxant responses to isoprenaline and BRL37344 were weakly antagonized by high concentrations of (+/-)-propranolol (10 and 100 microM) yielding pKB values of 5.7 with isoprenaline as the agonist and 5.5 with BRL37344 as the agonist. 4. The non-selective beta-adrenoceptor antagonist, (+/-)-alprenolol (1-100 microM) caused competitive antagonism of the relaxant responses to isoprenaline (pA2 value = 6.5). A similar pKB value was obtained when BRL37344 was used as the agonist (6.4). 5. Relaxant effects of isoprenaline and BRL37344 were also antagonized by ZD7114 (1-100 microM) yielding pA2 and pKB values of 6.3 and 6.7 respectively. 6. The low potencies of (+/-)-propranolol and (+/-)-alprenolol as antagonists of the relaxant responses to isoprenaline and BRL37344 indicate that both the agonists and antagonists employed in the current study may interact with beta 3-adrenoceptors in the rat isolated ileum. Contrary to the previous findings in guinea-pig ileum, where BRL37344 and ZD7114 were full agonists, in the current study, BRL37344 was a partial agonist and ZD7114 an antagonist at the beta 3-adrenoceptor in rat ileum.

Adrenergic beta-Agonists↗
PubMed1993

A comparison of transoesophageal atrial pacing and direct current cardioversion for the termination of atrial flutter: a prospective, randomised clinical trial.

OBJECTIVE: To compare the safety and efficacy of transoesophageal atrial pacing (TAP) with an easily swallowed pill electrode and direct current cardioversion (DCC) in patients with atrial flutter that was refractory to appropriate medical treatment. DESIGN: Prospective, randomised clinical trial. SETTING: Community based United States naval hospital. SUBJECTS: Twenty one consecutive patients with refractory atrial flutter selected consecutively from the inpatient cardiology consultation service. All patients were haemodynamically stable and medical treatment with a class IA or IC antiarrhythmic agent had failed. Eleven patients were treated with TAP and 10 patients were treated with DCC. INTERVENTIONS: Digoxin was given to all patients to control the ventricular rate to < 100/minute. MAIN OUTCOME MEASURE: Conversion to normal sinus rhythm and arrhythmias after cardioversion. RESULTS: Conversion to normal sinus rhythm was similar in both groups (TAP 8/11, DCC 9/10, p = 0.31). Arrhythmias after cardioversion including third degree heart block and non-sustained ventricular tachycardia were more frequent in the DCC group (TAP 0/11, DCC 6/10, p = 0.02). CONCLUSION: Transoesophageal atrial pacing with an easily swallowed pill electrode is safe, well tolerated, and is as efficacious as DCC for refractory atrial flutter.

Aged↗
PubMed1993

Rat tail flick reflex: magnitude measurement of stimulus-response function, suppression by morphine and habituation.

1. To quantitatively investigate a nocifensive behavioral response, we developed a method to measure the magnitude of the rat's tail flick reflex and its modulation. A radial array of force transducers measured forces of tail flicks (in rostral, horizontal, and vertical planes) elicited by graded noxious radiant thermal stimulation of the conscious rat's tail, from which the overall movement vector was calculated. 2. The rostrally directed component of tail flicks was always larger than dorsal or horizontal components; the latter was usually in a preferred (left or right) direction regardless of which side of the tail was heated. Tail flick force vectors increased from 40 to 46-52 degrees C and then leveled off. Stimulus-response functions were reproducible within and across rats and were fitted by second-order polynomial functions, whose correlation coefficients were similar when the left or right side of the tail was stimulated in separate sessions (r2 = 0.408 and 0.451, respectively). The inverse latency of tail flicks also increased with temperature in a manner fitted by a second-order polynomial (r2 = 0.707, 0.553 for left and right side, respectively). 3. Systemic administration of morphine (1 or 2 mg/kg ip) usually suppressed tail flicks in an all-or-none manner; i.e., flicks at all stimulus temperatures were either totally abolished (n = 7) or unaffected (n = 5) after morphine. In three rats, 1 mg/kg morphine suppressed tail flick magnitude subtotally, reducing the slope of the linear portion of the stimulus-response function. Morphine effects were reversed by the opiate antagonist naloxone. 4. Tail flick magnitude decreased over repeated trials of 44 degrees C heat stimuli delivered to one tail site, recovered after a 15-min rest period, and decremented more quickly with subsequent stimulus repetition. The decrement was less at long (2 or 4 min) than at short (1 min) interstimulus intervals, and high (50 degrees C) than at low (44 degrees C) stimulus intensities. The reflex decrement transferred to a nearby stimulus site in some rats, and was "dishabituated" after a noxious tail pinch. These observations are consistent with habituation of the tail flick reflex. 5. This method, therefore, provides a quantitative and reproducible measure of tail flick reflex magnitude that is sensitive to morphine. The underlying neural circuitry of the tail flick reflex is discussed in relation to limb withdrawal reflexes.

Afferent Pathways↗
PubMed1993

Increasing the dose intensity of chemotherapy in poor-prognosis metastatic non-seminoma.

The overall cure rate of patients with metastatic non-seminoma of the testis is high and a recent survey of 795 patients by the Medical Research Council indicated that 85% were alive 3 years after the start of chemotherapy. Two major categories of patients can be identified with a poorer prognosis. First are those with adverse prognostic factors at presentation defined by presence of one of the following factors: high tumour markers, more than 20 lung metastases, liver bone or brain metastases, mediastinal mass more than 5 cm. In these patients, the RMH is investigating accelerated chemotherapy employing a 7 day cycle, combined carboplatin and cisplatin and infusional bleomycin (C-BOP regimen). Of 21 patients followed for a median of 18 months, 18 (85%) have remained continuously disease free. The second adverse group are patients who have already failed first line chemotherapy. A multivariate prognostic factor analysis on 105 patients treated at the Royal Marsden Hospital indicates that adverse factors for salvage chemotherapy are the disease-free interval and the extent of disease at relapse. Our approach to patients with disseminated relapse includes high dose carboplatin and etoposide with autologous bone marrow support. With follow-up from 3-24 months, 7 of 11 patients treated with high dose chemotherapy remain continuously free from progressive disease. The need for an alkylating agent in the high dose combination is questionable.

Analysis of Variance↗