Search PubMed⌕ Search

Biomedical subjects

P Groves

Publications and source records attributed to P Groves.

29 records · Page 2Linked to original sources
PubMed1995

Role of endogenous bradykinin in human coronary vasomotor control.

BACKGROUND: Bradykinin is a potent vasodilator that acts through B2 kinin receptors to stimulate the release of endothelium-derived nitric oxide, prostacyclin, and hyperpolarizing factor. In this study, we investigated the contribution of endogenous bradykinin to vasomotor control in the human coronary circulation. METHODS AND RESULTS: The selective bradykinin B2 receptor antagonist HOE 140 was infused into the left main coronary artery (200 micrograms/min for 15 minutes) in 15 patients without significant coronary stenoses. Epicardial responses were evaluated by quantitative coronary blood flow with a Doppler flow-velocity wire. Flow-dependent dilation (n = 10; intracoronary papaverine) and acetylcholine responses (n = 5) were assessed before and after HOE 140. After HOE 140, there was a reduction in luminal area in the proximal (P < .001), mid (P < .001), and distal (P < .05) coronary arteries. HOE 140 led to an increase in coronary vascular resistance (P < .001) and a decrease in coronary blood flow (P < .001). After bradykinin B2 receptor blockade, there was a reduction in flow-dependent dilation (23.4 +/- 6.9% to 3.9 +/- 6.0%, P < .001), the extent of which correlated with the degree of basal vasoconstriction after HOE 140 in the same vessel segment (P < .05). Acetylcholine responses were unchanged after HOE 140. CONCLUSIONS: The results of this study demonstrate for the first time a role for endogenous bradykinin in mediating normal vasomotor responses in resistance and epicardial coronary vessels under basal and flow-stimulated conditions in the human coronary circulation.

Animals↗
PubMed1995

Evidence for the stochastic acquisition of cytokine profile by CD4+ T cells activated in a T helper type 2-like response in vivo.

The diversity of cytokine production patterns displayed by T cells activated in vivo was investigated by analyzing short-term antigen-specific CD4+ T cell clones and single CD4+ T cells derived from draining lymph nodes of mice undergoing a T helper 2 (Th2)-like response to keyhole limpet hemocyanin (KLH). On average, 2.7% of CD4+ lymph node cells gave rise to clones in the presence of the immunizing antigen and, of these, about 90% secreted interleukin-4 (IL-4) and 20% secreted interferon-gamma (IFN-gamma) when restimulated after 2 weeks in vitro. Almost all IFN-gamma-producing clones co-produced IL-4. The definition of clones as positive or negative for cytokine synthesis depended on assay sensitivity, however, since their titers were distributed continuously from the threshold of detection over at least a 1000-fold range. Reverse-transcription polymerase chain reaction analysis of 59 clones revealed multiple patterns of co-expression of IL-2, IL-3, IL-4, IL-6, IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA. Although most clones contained detectable IL-4 and IL-6 mRNA and a minority contained IFN-gamma mRNA, only 1 clone expressed the canonical Th2 cytokine profile. The observed frequencies of mRNA co-expression for most of the six cytokines (including IL-4 with IFN-gamma), and the frequency of co-secretion of IL-4 and IFN-gamma, were not significantly different from those predicted for random association. Independent regulation of IL-4 and IFN-gamma mRNA expression was confirmed at the single-cell level in a polyclonal population of KLH-primed CD4+ cells, among which co-expression of these cytokines again occurred at the frequency predicted for a random event. The data suggest that the polarization of this immune response towards a Th2 cytokine profile is achieved by altering the probabilities of expression of the IL-4, IFN-gamma and other cytokine genes at the population level, rather than by selective expansion of a distinct T cell subset.

Animals↗
PubMed1994

The structure of an asymmetric dimer relevant to the mode of action of the glycopeptide antibiotics.

BACKGROUND: Glycopeptide antibiotics of the vancomycin group are of crucial clinical importance in the treatment of methicillin resistant Staphylococcus aureus (MRSA)--the often lethal 'super-bug'--characterized by its resistance to a wide range of antibiotics in common use. The antibiotics exert their physiological action by blocking cell wall synthesis through recognition of nascent cell wall mucopeptides terminating in the sequence -D-Ala-D-Ala. Evidence suggests that the antibiotics are able to enhance their biological activity by the formation of homodimers, and this is supported by the observation that dimerization and peptide binding in vitro are cooperative phenomena. The basis of this enhancement is not understood at the molecular level. RESULTS: The first detailed structure of a dimeric glycopeptide antibiotic, that of eremomycin, is presented based upon solution NMR data. The overall structure of the dimer complex is asymmetric. The source of this asymmetry--a parallel alignment and mutual interaction of the disaccharides--appears to promote dimerization through specific sugar-sugar recognition. CONCLUSIONS: A molecular basis for the observed cooperativity of cell wall peptide binding by eremomycin is evident from these studies of the dimer. The carboxylate anion of the cell wall component, which is crucial to binding, forms an amide-mediated ion-pair interaction to the alkylammonium ion of the ring 6 sugar in the other half of the dimer making the structure and positioning of this sugar important in mediating cooperativity.

Amino Acid Sequence↗
PubMed1994

Rapid establishment of a stable IL-4/IFN-gamma production profile in the antigen-specific CD4+ T cell response to protein immunization.

Development of the antigen-specific murine T cell response to immunization with keyhole limpet hemocyanin (KLH) in adjuvant has been monitored with direct limiting dilution analysis of CD4+ cells in draining lymph nodes (LN) and measurement of the cytokines produced by their clonal progeny. In vivo, the response to immunization suggested a major role for IL-4 and a minor role for IFN-gamma since IL-4 mRNA levels increased and IFN-gamma mRNA levels declined in LN over the first 3 days, and KLH-specific serum antibodies were mainly of IgG1 class with lower levels of IgE and IgG2a. Antigen-specific clonogenic cells were first detected in LN at day 4, at which time they comprised approximately 8% of the total CD4+ LN cell pool, declining to 1-2% from day 7 until at least 6 weeks after immunization. These clonogenic cells expressed high levels of surface CD44 (Pgp-1) both early and late in the in vivo response. Over the whole of the time span from day 4 to 6 weeks after immunization, most antigen-specific cells gave rise to clones that secreted IL-4 and a smaller proportion gave rise to IFN-gamma-secreting clones. By contrast, polyclonally activated CD4+ cells from untreated mice preferentially gave rise to clones with the converse cytokine profile. We conclude that a stable ratio of antigen-specific CD4+ cells committed to IL-4 or IFN-gamma synthesis is established within the first 4 days after KLH immunization and, contrary to prediction, does not evolve towards a more restricted cytokine profile during the primary response.

Animals↗
PubMed1993

Assessing long term backache after childbirth.

OBJECTIVES: To investigate the factors associated with long term backache after childbirth, to assess all women reporting new onset long term backache, and to investigate any relation with pain relief in labour. DESIGN: Data collected from obstetric records and postal questionnaires or telephone interviews on morbidity after childbirth from all women delivering their first baby between March 1990 and February 1991, followed by analysis of data collected from outpatient consultations. SETTING: St Thomas's Hospital, London. SUBJECTS: Questionnaires were sent to 1615 women who had delivered their first baby in the defined period; 1015 either replied by post or were contacted by telephone. RESULTS: 299 women (29.5% of responders) reported backache lasting more than six months and of these 156 (15.4%) said they had had no back problems previously. Those women who had received epidural analgesia in labour were significantly more likely to report new onset backache (17.8%; 95% confidence interval 14.8% to 20.8%) than those who did not (11.7%; 8.6% to 14.8%). Younger women, unmarried women, and those reporting other antenatal symptoms were significantly more likely to report new long term backache. The 156 women reporting new backache were asked to attend an outpatient clinic and 36 (23%) did so. The majority had a postural backache which was not severe. Psychological factors were present in 14 women. CONCLUSIONS: Though new long term backache is reported more commonly after epidural analgesia in labour, it tends to be postural and not severe. There were no differences in the nature of the backache between those who had or had not received epidural analgesia in labour.

Adult↗
PubMed1993

Is opioid loading necessary before opioid/local anaesthetic epidural infusion? A randomized double-blind study in labour.

The effects of two different epidural loading doses administered before starting an opioid/low dose local anaesthetic infusion were examined in a randomized double-blind study during labour. Forty mothers were given either 10 ml 0.25% plain bupivacaine or 10 ml 0.125% plain bupivacaine containing 5 mcg of sufentanil followed in all cases by epidural infusion of 0.08% plain bupivacaine containing 0.2 mcg/ml of sufentanil, which was continued into the second stage. The quality of analgesia did not differ significantly between the groups in either the first or the second stage of labour: in each group 75% of women required 0 or 1 top-up during labour and verbal numerical pain scores were similar. Over 80% of women in each group reported a pain free second stage of labour. There were no differences in the mode of delivery between the groups with 60% of women in each group having a spontaneous vaginal delivery. The proportion of women with motor block increased with the duration of the epidural infusion, with no difference between the groups. There was no difference in the degree of maternal satisfaction assessed 24 hours after delivery, with 80% of women in each group awarding the maximum verbal numerical score for their satisfaction with epidural analgesia. The incidence of maternal side effects (nausea, vomiting, drowsiness and pruritus) was similar in the 2 groups as was neonatal outcome, assessed by Apgar and neurological and adaptive capacity scores and umbilical artery and vein pH. We conclude that opioid loading before opioid/low-dose bupivacaine epidural infusions is unnecessary.

Journal Article↗
PubMed1993

Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease.

OBJECTIVE: To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN: 40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING: Tertiary referral centre. SUBJECTS: Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES: Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS: Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS: The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral vascular surgery.

Aged↗
PubMed1967

Evoked cortical potentials: relation to visual field and handedness.

The amplitiude of evoked responses of occipital cortex in man depends on the visual field in which the stimulus appears. Greater responses occurred repeatedly for two of three subjects, both left-handed. when the stimululs appeared in the left field than in the right. Subsequent tests of 13 right- and 13 left-handed males indicted that the magnitude of the response of the right lobe, relative to that of the left, was greater for left-handed individuals. We conclude that the difference in amplitude between the two lobes is related to handedness.

Cerebral Cortex↗