Search PubMed⌕ Search

Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 127 records · Page 7Linked to original sources
PubMed1995

Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum.

A gene encoding a novel cdc2-related protein kinase has been identified in Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to regions that are conserved in members of the cdc2 gene family. This gene, called Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA gene family, members of which are negative regulators of cell growth in vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific accumulation of mRNA in gametocytes.

Amino Acid Sequence↗
PubMed1995

COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies.

We report the deduced protein sequence and preliminary characterization of Pfg377, a novel sexual stage antigen of Plasmodium falciparum. An initial cDNA clone (Pfg377-1) encoding the N-terminal 755 amino acids of Pfg377 was isolated by transfecting a 3D7 gametocyte cDNA library into COS7 cells and selecting using a pool of anti-Pfs230 monoclonal antibodies. The protein encoded by Pfg377-1 included an N-terminal hydrophobic signal sequence, but no apparent transmembrane anchor. Instead, the particular cDNA clone selected was fused in-frame at its 3' end with the coding sequence for the human decay acceleration factor membrane anchor, which had been deliberately placed downstream of the vector polylinker in order to attach potential fusion proteins onto the COS cell surface. Northern blots probed with the Pfg377-1 cDNA demonstrated cross-hybridization to a single approximately 9.5-kb transcript, which was present only in sexual stages, and not in a sexual stages. DNA hybridization was used to obtain a series of overlapping genomic clones which collectively yielded the complete DNA sequence for Pfg377. There are no introns within the gene, which contains a 9360-bp open reading frame and encodes a 377-kDa protein. The Pfg377 protein is highly hydrophilic, and has an essentially non-repetitive structure, with only four very limited regions of tandem repeats. The Pfg377 gene resides on chromosome 12, and immunoelectron microscopy with two different anti-Pfg377 polyclonal antisera raised against two separate recombinant sub-fragments of the protein both indicated that the antigen is located in electron-dense organelles of the gametocytes--the osmiophilic bodies--which are proposed to play a role in parasite emergence from the erythrocyte during gametocyte maturation in the Anopheles mosquito midgut. Although it was selected with anti-Pfs230 antibodies, comparison of the sub-cellular locations and protein sequences of Pfg377 and Pfs2 show them to be completely distinct antigens. We hypothesize that Pfg377-1 was initially isolated because it expresses an epitope which is recognized by (i.e., cross-reacts with) one of the anti-Pfs230 monoclonal antibodies used to select the original transfected COS cells.

Amino Acid Sequence↗
PubMed1995

Clinical disease and pathogenesis in malaria.

This is the report of a meeting held in Ahungalla, Sri Lanka, 16-19 January 1994, under the sponsorship of the Rockefeller Foundation, Health Sciences Division. The meeting was initiated jointly by the Rockefeller Foundation and the TDR Special Programme of the World Health Organization in order to bring together scientists with a wide spectrum of experience relating to malarial disease and pathogenesis. The objective was to generate interdisciplinary discussion ranging from the clinical pictures of malarial infections and their impact in different parts of the world, to current investigations on mechanisms of pathogenesis and clinical immunity and the genetic determinants in human and parasite populations affecting the nature of the disease.

Journal Article↗
PubMed1995

Randomized cross-over study of a 21-day versus a 28-day hormone replacement therapy (HRT).

OBJECTIVE: To compare the occurrence of climacteric symptoms at two points in the cycle, identified as minE (phase of minimum estrogen effect) and MaxP (phase of maximum progesterone effect). METHODS: Prospective randomized cross-over study in postmenopausal women currently on HRT comparing two opposed, sequential formulations: a regimen of 21 tablets containing estradiol valerate (EV) opposed with cyproterone acetate (CPA) in the last 10 tablets, versus a regimen of 28 tablets of conjugated equine estrogens (CEE), the last 12 tablets of which were taken together with norgestrel (NG). OUTCOME MEASURES: Incidence of 24 climacteric complaints assessed at the specified days of the cycle corresponding to minE (day 6 or 7) and MaxP (day 27 or 28) RESULTS: Contrary to the hypothesis that estrogen-dependent symptoms will recur at minE of the 21-day regimen, no significant differences were noted with the regimen containing 28 days of CEE, which served as the control. There were more complaints with the CEE+NG formulation at both minE and MaxP. Of the 38 patients, 63% preferred the EV+CPA regimen, 18.4% the CEE+NG regimen and 18.4% rated both preparations as equal. CONCLUSIONS: The 7-day pause in the 21-day formulation containing EV+CPA did not affect efficacy; it was as effective in relieving climacteric symptoms as the regimen containing 28 days of estrogen. Based on the frequency of complaints both at minE and MaxP, the EV+CPA formulation induced a more acceptable symptom and mood profile.

Adult↗
PubMed1995

Activation and inhibition of the endogenous opioid system in human heart failure.

BACKGROUND: In a canine model of congestive heart failure beta endorphin concentrations were high and opioid receptor antagonists exerted beneficial haemodynamic effects. In humans previous studies have suggested that opioid peptides may modify the perception of breathlessness and fatigue in heart failure. METHODS: Plasma concentrations of beta endorphin were measured in patients with acute and chronic heart failure and cardiogenic shock. A subgroup of eight patients with New York Heart Association (NYHA) class III-IV heart failure was assessed for acute haemodynamic effects of naloxone, an opioid receptor antagonist. A separate group of 10 patients with class II-III heart failure, was randomised to a double blind placebo controlled study of the effects of intravenous naloxone on cardiopulmonary exercise performance. RESULTS: Plasma concentrations of beta endorphin were usually normal in patients with chronic heart failure and did not correlate with severity as assessed by NYHA class. In 29% of patients with acute heart failure and 71% of those with cardiogenic shock beta endorphin concentrations were high. The median concentration in the cardiogenic shock group was significantly higher than in either of the two heart failure groups and there was some evidence of a relation between beta endorphin concentrations and survival. At the doses tested, naloxone was unable to modify systemic haemodynamics, exercise performance, or symptoms in patients with chronic congestive heart failure. CONCLUSIONS: Circulating concentrations of beta endorphin are usually normal in patients with chronic congestive heart failure. Inhibition of the endogenous opioid system is unlikely to have therapeutic potential in heart failure.

Acute Disease↗
PubMed1995

An evaluation of integrated cardiopulmonary exercise testing in a pulmonary function laboratory.

Clinical exercise testing has been used mainly to assess the cardiac response to exercise. Integrative cardiopulmonary exercise tests (CPET) involving the measurement of the ventilatory, circulatory and metabolic response to exercise has largely been a research tool. We analysed the results of one hundred tests randomly chosen from a total of 472 exercise tests performed between January 1992 and June 1993 as clinical investigation in a pulmonary function laboratory. CPET was used (a) to identify the cause of effort limitation in patients where more than one illness could be relevant (26); (b) to obtain an objective measure of the exercise capacity of patients with respiratory or cardiac disease (31); (c) as monitor of response to treatment (11) and (d) in the investigation of unexplained dyspnoea (32). In 94 of the 100 cases CPET was able to provide an answer to the specific clinical question posed. In patients with unexplained dyspnoea (CPET identified a group who exhibit an inappropriate hyperventilatory response to exercise with no supportive evidence of cardiopulmonary disease. In a small minority of cases CPET gave non-specific results. We conclude that CPET is a useful investigation in the management of patients with cardiopulmonary disease and complements the various other investigations offered by a pulmonary function laboratory.

Adolescent↗
PubMed1995

Ventilatory and gas exchange abnormalities on exercise in chronic heart failure.

The mechanism of breathlessness on exertion in patients with chronic heart failure are still not fully understood. We therefore investigated the effects of ventilatory and gas exchange abnormalities on exercise capacity in chronic heart failure. Exercise testing was performed in 30 patients with exertional breathlessness due to chronic heart failure and in 30 controls, using continuous transcutaneous blood gas monitoring. Maximal symptom-limited oxygen consumption as (V'O2) as a percentage predicted was reduced in patients (45 +/- 10%; mean +/- SD) compared to controls (87 +/- 7). The ventilatory response (minute ventilation/carbon dioxide production (V'E/V'CO2)) was significantly increased in patients compared to controls (39.9 +/- 7.7 and 25.9 +/- 3.6, respectively). The dead space to tidal volume ratio (VD/VT) was raised in patients compared to controls at rest (0.45 +/- 0.04 vs 0.35 +/- 0.02, respectively) and this persisted on exertion (0.40 +/- 0.05 in patients and 0.20 +/- 0.05 in controls). At maximal symptom-limited exercise, V'E/V'CO2 was inversely related to the % predicted V'O2 in patients, but not in controls (r = -0.62 and r = -0.24, respectively). In patients, V'E/V'CO2 was significantly correlated with VD/VT at maximum exercise (r = 0.82). Patients with chronic heart failure have a significant degree of "wasted ventilation" on exertion, which is associated with increased ventilatory response. The increased ventilatory response on exertion appears to contribute to exercise limitation in these patients.

Adult↗
PubMed1995

Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.

STUDY OBJECTIVE: Awareness of bronchiectasis on the part of clinicians has been low in recent years, although it was previously well recognized. We believe that bronchiectasis is underdiagnosed, and that current literature is skewed toward the esoteric etiologies of bronchiectasis. DESIGN: We reviewed the clinical, radiologic, microbiologic, and physiologic findings in 123 well-studied patients with proved bronchiectasis. SETTING: The University of Texas Health Center at Tyler Hospital and Clinics. MEASUREMENTS AND RESULTS: There were 38 men and 85 women with a mean (+/- SD) age of 57.2 +/- 16.7 years; 55% were lifetime nonsmokers. Diagnosis was confirmed with CTs of the chest in 56%, by bronchogram in 28%, and surgery with the remainder. Seventy percent of patients gave a history of an antecedent potentially causative event for the bronchiectasis, usually pneumonia. Symptoms of bronchiectasis included chronic cough with the production of purulent sputum, hemoptysis, recurrent fever, and pleurisy. The finding of crackles on chest examination was the rule (70%) with wheezing present in 34% of the group. Pulmonary function studies documented airway obstruction to be present in 54% of the lifetime nonsmokers. The chest radiographs were abnormal in 91.3%, showing fibrotic stranding and infiltrates. A variety of pathologic microbial flora, particularly Pseudomonas aeruginosa and other opportunistic organisms, were isolated from the sputum. Patients who had smoked had much the same picture as nonsmokers, although they had a greater degree of airway obstruction. CONCLUSIONS: A characteristic clinical picture of bronchiectasis emerges after review and evaluation of these data. Knowledge of this picture should allow ready recognition of the disease.

Adult↗
PubMed1995

Primary extra-thoracic T-cell non-Hodgkin's lymphoma of childhood. The United Kingdom Children's Cancer Study Group.

Between 60-80% of non-Hodgkin's lymphoma (NHL) of T-cell lineage in children, present with primary mediastinal disease. On current therapy, this and nodal low-stage disease are associated with a relatively favourable outcome. In order to evaluate whether the primary site of disease is a prognostic factor, we examined the clinical characteristics and outcome of 36 children with primary extrathoracic T-cell NHL diagnosed during a 7-year period by the United Kingdom Children's Cancer Study Group. Eight, eight, 11 and nine children had stage I, II, III and IV disease, respectively. The primary site of disease was nodal in 22, skin and subcutaneous tissue in five, abdominal in three, bone in three and at other sites in three. Eighteen (50%) had lymphoblastic, ten (28%) large cell anaplastic (LCA) and seven (19%) pleomorphic large or medium cell (PLC) tumours. In one child the histology was inconclusive. All children with lymphoblastic, three with LCA, three with PLC disease and one with unknown histology were treated on intensive, sustained and continuous leukaemia protocols. Ten, seven with LCA and three with PLC, were treated on regimens of short duration pulsed therapy and one child with PLC with radiotherapy only. The three-year event-free survival (EFS) was 78% for the group as a whole. Those with stage IV lymphoblastic disease had a significantly worse prognosis (p < 0.0005). Primary site of disease, gender, therapeutic regimen and histology were not predictive for survival. In primary extrathoracic T-cell NHL with lymphoblastic histology, leukaemia-like therapy is recommended. For non-lymphoblastic disease, in particular the Ki-1 positive tumours, evidence suggests that short duration pulsed therapy may be optimal.

Adolescent↗
PubMed1994

Is evidence for homoeopathy reproducible?

We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?

Adult↗
PubMed1994

Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p < 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

Acute Disease↗
PubMed1994

Randomized trial of adrenaline injection and laser photocoagulation in the control of haemorrhage from peptic ulcer.

Forty-nine consecutive patients with bleeding from peptic ulcers that would conventionally have required surgical intervention were randomized to receive endoscopic injection of adrenaline (1:10,000) or laser photocoagulation. Patients were included only if they had a visible vessel at endoscopic examination. Five patients proceeded directly to surgery and, of the remaining 44, 21 received laser photocoagulation and 23 injection therapy. Haemostasis was achieved initially in all patients. There was one rebleed in the group of patients who received laser treatment and four in those treated by injection. All five patients underwent further endoscopic haemostasis according to the initial randomization. Haemostasis was again achieved in all cases, but the patient who had undergone laser treatment suffered recurrent haemorrhage after a further 48 h and subsequently died. Overall, one of the 21 patients receiving laser treatment died compared with none of the 23 injected with adrenaline. Injection of adrenaline achieves similar results to laser photocoagulation for bleeding peptic ulcer.

Adult↗
PubMed1994

Cellular location and temporal expression of the Plasmodium falciparum sexual stage antigen Pfs16.

The temporal expression during gametogenesis and the cellular location of the sexual stage specific protein Pfs16, a putative integral membrane protein of Plasmodium falciparum, was investigated using two monoclonal antibodies, 2G7 and 93A3A2. Using sorbitol synchronised, in vitro gametocyte cultures along with immunofluorescence assays, the time at which Pfs16 is first expressed during gametogenesis has been estimated to 35 hours post merozoite invasion. By immunofluorescence assays on thin blood smears monoclonal antibodies specific for Pfs16 react strongly with the gametocyte and also with vesicles within the red blood cell cytoplasm, many of which connect with the gametocyte cell. Purification of parasitophorous vacuole membranes from mature and immature gametocytes and immunoelectron microscopy on gametocytes during gametogenesis have allowed us to locate Pfs16 to the parasitophorous vacuole membrane. During gametogenesis this membrane is shed along with the red blood cell membrane. Immunofluorescence assays and immunoelectron microscopy studies of emerged gametes indicate that in a minority of cases the parasitophorous vacuole membrane along with Pfs16 can be retained to some extent on the gamete surface.

Animals↗
PubMed1994

Maternal inheritance of extrachromosomal DNA in malaria parasites.

Plasmodium falciparum has two extrachromosomal genomes, the mitochondrial 6-kb DNA element and the 35-kb circular DNA. The mitochondrial gene cytochrome b on the 6-kb element has been shown to be inherited uniparentally. In order to ascertain whether the route is maternal or paternal we have examined preparations of male and female gametes of the closely related Plasmodium gallinaceum for the presence of extrachromosomal DNA. DNA from purified preparations of gametes was hybridised to probes for both the 6-kb and 35-kb extrachromosomal genomes. Both probes hybridised to the preparation of Plasmodium gallinaceum female gametes but not to that of the males. We conclude that the extrachromosomal DNAs of malaria parasites are transmitted maternally.

Animals↗
PubMed1994

Breathlessness in microvascular angina.

In patients with microvascular angina (MA), there is some evidence from studies of plethysmography, that there are widespread microvascular abnormalities. In addition to exertional chest pain, all these patients complain of breathlessness, with no evidence of airways obstruction or resting left ventricular dysfunction. Progressive exercise testing was performed in 12 age and sex matched controls and 12 patients (three males), in whom the diagnosis of MA was established on the basis of exertional chest pain, abnormal thallium scans, and an attenuated myocardial flow response to a vasodilator challenge, with angiographically entirely normal epicardial vessels. Symptom limited exercise was performed with on line ventilation and expired gas analysis, measuring minute ventilation, oxygen consumption and carbon dioxide production and arterial blood gas values using a transcutaneous system. Anaerobic threshold was calculated by curve fitting a plot of oxygen consumption against carbon dioxide production. Compared to controls (49.7 +/- 7.3 SD% predicted maximum VO2) in patients with MA, the anaerobic threshold was reduced (41.6 +/- 5.82; P < 0.02) although still within accepted normal limits. Maximal (symptom limited) oxygen consumption, as a percentage of predicted, was reduced 60.73 +/- 16.51 compared to 87.21 +/- 5.2 (P < 0.003). The ventilatory response (VE/VCO2 l l-1 CO2 output) was significantly increased in the MA patients compared to controls (35.9 +/- 8.01 and 27.5 +/- 3.08, respectively; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Splanchnic blood flow changes in the presence of hepatic tumour: evidence of a humoral mediator.

Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-1 min, s.e. 21.5, vs 51.7 mmHg ml-1 min, s.e. 7.4, P < 0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases.

Animals↗
PubMed1994

Protracted venous infusion 5-fluorouracil and interferon-alpha in advanced and refractory colorectal cancer.

BACKGROUND: The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-alpha, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU. PATIENTS AND METHODS: Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-alpha was added and further outcome evaluated. RESULTS: One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-alpha added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-alpha addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-alpha gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months. CONCLUSIONS: Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-alpha at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-alpha can be recommended as a modulator of 5-FU in the clinical setting.

Adult↗