Search PubMed⌕ Search

Biomedical subjects

K Phillips

Publications and source records attributed to K Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1994

Electrostatic activation of Escherichia coli methionine repressor.

BACKGROUND: The three-dimensional structure of the Escherichia coli methionine repressor (met repressor) is relatively unperturbed by the binding of its corepressor, S-adenosylmethionine (SAM), and of operator DNA. The positively charged corepressor binds to sites on the repressor remote from the DNA-binding site, and despite the lack of induced structural change is able to raise the affinity for operator DNA by a factor of up to 1000. Neutral corepressor analogues also bind to the repressor, but do not increase operator affinity. These observations suggest that the corepressor effect may be electrostatic. RESULTS: Using the program DELPHI, we have calculated electrostatic potentials for the repressor and its complexes, and have obtained results consistent with an electrostatic model for repressor activation. The positive potential originating from the corepressor is propagated through the repressor-operator complex, and is significant at DNA phosphate groups buried in the protein-DNA interface. The rank order of calculated electrostatic interaction energies for complexes with SAM, and two closely-related analogues, is in agreement with experimental measurements of the corresponding repressor-operator affinities. CONCLUSION: Long-range (> 10 A) electrostatic interactions between bound corepressor and operator phosphate groups in the repressor-operator complex may be sufficient to explain repressor activation Met repressor could, therefore, be an electrostatically triggered genetic switch.

Apoproteins↗
PubMed1994

Relationship of burst-forming-unit-erythroid progenitors and their DNA-synthesis stage to fetal hemoglobin levels in hydroxyurea-treated patients with sickle cell anemia.

DNA-synthesis stage and total number of circulating burst-forming-units-erythroid (BFU-E) have been inversely correlated with hemoglobin F levels in the peripheral blood, as well as in the cells from the BFU-E-derived colonies obtained from homozygous sickle cell anemia (SS) patients during steady state. Similar studies in SS patients treated with cytotoxic agents have not been reported. However, regeneration of the erythroid marrow that follows the cytoreduction phase of chemotherapy has been suggested as one of the mechanisms of stimulation of fetal hemoglobin synthesis. Therefore, a longitudinal study of hemopoiesis in hydroxyurea-treated SS patients was conducted. Thirty-two sets of hemopoietic studies, including total circulating BFU-E and S-phase BFU-E, were obtained from three patients treated with hydroxyurea. A dose-dependent decrease in total BFU-E colonies occurred in peripheral blood of all three patients (r = -0.58, -0.85, and -0.97, respectively, with each P < 0.05). There was a strong positive correlation between hydroxyurea dose and fetal hemoglobin levels in two of the three patients who responded clinically (r = 0.89618 and 0.88632, respectively, with each P < 0.01). When data from all patients were combined (n = 32), there was a strong, inverse, linear relationship between total number of BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (r = -0.6649 and -0.7404, respectively, with each P < 0.0001). A stronger, curvilinear, multiple relationship was detected between total BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (R = 0.8351 and 0.8602 with each P < 0.0001).

Adolescent↗
PubMed1994

Evaluation of a training course on sexual counselling in a drug work setting.

It has been repeatedly reported that while risks associated with the injecting behaviour of drug users has been reduced, no parallel changes have been made in sexual risk behaviour. Counselling advice to clients attending drug unit services has not focused sufficiently on the sexual behaviour of this client group. The present study evaluates the impact of a 4-day tailored training course on the counselling practices of two teams of drug workers at a London hospital. The course was designed following the experience and evaluation of a more general training course on sexual issues, and included information, group discussions, experiential learning and skills training. Results indicate that though there were no significant behavioural changes, some attitudinal changes have taken place; training appears to have increased the staff's awareness of the importance of sexual counselling and reduced the perceived difficulty of discussing certain specific sexual issues. The implications of single-agency training courses are discussed and recommendations are made for future training courses on the basis of the findings of this study.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Intestinal kinetics and dynamics of Escherichia coli heat-stabile enterotoxin in suckling mice.

The heat-stabile enterotoxin produced by Escherichia coli (ST) induces diarrhea by binding to receptors on intestinal cells, activating guanylyl cyclase, and increasing cyclic GMP. High- and low-affinity receptors for this toxin have been identified previously. ST induces intestinal secretion in suckling mice in picomole doses, suggesting a role for high-affinity receptors in this process. The present studies examine the relative roles of high- and low-affinity receptors in this process. The time course of changes in free ST concentrations in suckling mouse intestine was determined after intragastric inoculation. Also, binding characteristics of high- and low-affinity receptors and their coupling to guanylyl cyclase were defined in intestinal membranes from suckling mice. Intestinal concentrations of toxin and receptor binding characteristics empirically determined were used in a dynamic model correlating fractional occupancy of high- and low-affinity receptors with intestinal secretion to estimate their relative contributions to ST-induced diarrhea.

Animals↗
PubMed1994

'Nursing should become a research-based profession'--has it?

I decided to write this article to promote discussion among my colleagues after my experience of doing clinical research of my own. I did a small clinical trial on the use of Sea-Bands (wrist sweat bands) to put pressure on an acupuncture site to relieve postoperative nausea. This has been published in the Nursing Times. I am a theatre sister and have a reasonably academic background having obtained both an Open University BA and a teaching certificate plus a number of nursing courses. Therefore, I had good access to staff and patients and enough confidence to embark on the project. However, I had no experience in research work, and perhaps it is not surprising to find that there is no back-up within 'the system' to sustain this type of work. I went to everyone that I could think of for help and advice to formulate my data collection protocol. I gleaned small nuggets of advice from the local college of nursing, from the community research liaison doctor, and from the ethical committee chairman but it was a long hard slog which would have deterred me from starting had I realised at the outset how many hours of my own time it would take me.

Humans↗
PubMed1993

Sexual issues and condom use among injecting drug users.

Recent surveys of injecting drug users reveal that their injecting behaviours have changed in the light of HIV, but their sexual behaviours have not and, in particular, they remain reluctant to use condoms to reduce the risks of sexual transmission. In an attempt to explore this issue further the present study assessed the behaviours and attitudes of injecting drug users to sexual issues, including condom use. Condom use was low. Obstacles to their use included for some a desire to conceive, for many a belief in their infertility, a perceived invulnerability to HIV infection through their sexual behaviour patterns, a dislike of condoms and difficulty in negotiating condom use with partners. The lifestyle of drug users may also have an influence on condom use. Many drug users funded their habit through illegal activities including prostitution, theft and fraud. The association between these and other factors and condom use are explored.

Adult↗
PubMed1993

Antibacterial action of the urease inhibitor acetohydroxamic acid on Helicobacter pylori.

The urease inhibitor acetohydroxamic acid (AHA) was assessed for its bacteriostatic and bactericidal effects on Helicobacter pylori. For eight isolates of H pylori, the minimum inhibitory concentration (MIC) was either 200 mg/l or 400 mg/l. Interactions between AHA and antimicrobial drugs used to treat H pylori were also determined. For most isolates AHA reduced the MIC for colloidal bismuth subcitrate (CBS), tetracycline, metronidazole, and amoxicillin. In a few isolates, however, AHA increased the minimum bactericidal concentration (MBC) for these antimicrobial treatments. In vitro AHA is active against H pylori and it interacts with other agents directed against H pylori.

Amoxicillin↗
PubMed1992

A novel nuclear protein which binds to G gamma and A gamma globin promoters and modulates hemoglobin synthesis in K562 cells.

Nuclear extract of human erythroleukemic cell line K562 contains a 70 kDa protein which is gradually reduced when cells are induced to express globin genes by 25 microM hemin. When globin synthesis was inhibited by cycloheximide (100 micrograms/ml) or Actinomycin D (1 microgram/ml), the disappearance of this protein was prevented. The 70 kDa nuclear protein exhibited strong binding to G gamma and A gamma globin promoters but not to beta-globin promoter. This suggests that this 70 kDa nuclear protein may be involved in the regulation of fetal globin gene expression.

Base Sequence↗
PubMed1992

Hepatitis B screening and immunization for people with a mental handicap in Southampton: costs and benefits.

The residential population in a long-stay hospital and its associated local-based hospital units was screened for markers of hepatitis B infection. An immunization programme was then undertaken for residents found to be at risk. The authors found that an initial screening gives valuable information, is cost effective and better than a blanket immunization policy for all residents. Other benefits included opportunities to emphasize the importance of vaccination for staff members, and for staff education in infection control measures, especially in relation to hepatitis B.

Adolescent↗
PubMed1992

Randomized trial of amniotomy in labour versus the intention to leave membranes intact until the second stage.

OBJECTIVE: To compare by randomized prospective clinical trial the outcome of labours which are managed with the intention to leave the membranes intact, compared with the practice of elective artificial rupture of the membranes (ARM) in early established labour. DESIGN: Prospective randomized controlled trial of low risk women admitted in spontaneous labour, with intact membranes. SETTING: The labour ward of St. James's University Hospital, Leeds, UK. SUBJECTS: 362 women in spontaneous labour with intact membranes and no evidence of fetal distress, between 37 and 42 weeks gestation. During the course of the trial it was found that some randomization cards could not be accounted for and a system of daily checks was instituted. The results were analysed for all recorded women (n = 362) and after institution of the more rigorous system (n = 120). MAIN OUTCOMES MEASURED: The duration of each phase of labour, epidural rate, prevalence of an abnormal cardiotocograph (CTG) (assessed blind), method of delivery and neonatal outcome. RESULTS: 178 of the 183 women (97%) in the ARM group had their membranes ruptured in early labour, and 83 (46%) of the 179 women allocated to non-intervention had ARM performed at some stage. A significant decrease in the duration of labour (mean 8.3, SD 4.1 h vs mean 9.7, SD 4.8 h, n = 156; P = 0.05) was found amongst primigravidae allocated to ARM when compared with non intervention. The duration of the second stage of labour was unaffected. In the ARM group the epidural rate was higher and labour was more often complicated by CTG abnormalities. There were no differences in the method of delivery, fetal condition at birth (cord blood lactate, Apgar score) or postpartum pyrexia between the ARM and non-intervention groups. The same trends were observed when analysis was confined to women entered into the trial after the system of rigour was instituted. CONCLUSION: Routine ARM results in labour that is slightly shorter than if the membranes are allowed to rupture spontaneously but more epidurals are used suggesting that labour is more painful. There are fewer fetal heart rate abnormalities if the membranes are left intact but amniotomy has no effect on fetal condition at birth.

Amnion↗
PubMed1992

Clinical and hemodynamic sequelae of lower-extremity, deep-vein thrombosis after total joint arthroplasty.

To determine the long-term sequelae of lower-extremity deep-vein thrombosis (DVT) after total hip or knee arthroplasty, 25 patients with venographically proven lower-extremity DVT were studied. A study group of 16 patients was available 14 months postoperatively. The results of clinical and hemodynamic evaluation were compared with those of a randomly selected group of patients who had negative venographic findings after total joint arthroplasty. There were no statistically significant differences in calf pain or swelling between the two groups. The presence of venous varicosities and pigmentation were unreliable indicators of the post-thrombotic syndrome. There were no statistically significant differences in vein patency, valve competency, and venous recovery times. There was a high incidence of hemodynamic abnormalities in the historically uninvolved extremities of patients with postoperative DVT.

Aged↗
PubMed1991

Occupational asbestos exposure and mesothelioma risk in Los Angeles County: application of an occupational hazard survey job-exposure matrix.

We evaluated the newly available National Institute for Occupational Safety and Health (NIOSH) National Occupational Hazard Survey (NOHS) job exposure matrix (JEM) by considering mesothelioma risk from asbestos exposure. We applied this system (NOHS-JEM) to the Los Angeles County Cancer Surveillance Program (CSP) to see how many cancer cases could be assigned asbestos exposure and how asbestos exposure affected mesothelioma risk. Using the same CSP data, our "experts" classified asbestos exposure simply by occupation and industry. Both exposure classifications were divided into low and high; the NOHS-JEM by the number of exposed people per couplet, and ours by judgements of intensity. Odds ratios (OR) for mesothelioma risk for low and high asbestos exposure for the NOHS-JEM were 2.0 (95% C.I. 1.2-3.4) and 2.5 (95% C.I. 1.2-4.8). For ours, corresponding risks were 1.6 (95% C.I. 1.1-2.4) and 6.3 (95% C.I. 2.5-15.1). Our system was able to assign more cases to couplets then the NOHS-JEM (35,895 to 22,369). Three limitations of the NOHS-JEM were that many occupation-industry couplets were not classified at all, many couplets associated with past asbestos exposure (before the 1972-1974 NOHS survey) were not classified as asbestos exposure, and no assessment of intensity was made. These limitations may apply to other exposures and should be carefully considered before the NOHS-JEM is applied to other case-control studies.

Adolescent↗
PubMed1991

A novel process for preparing an acellular pertussis vaccine composed of non-pyrogenic toxoids of pertussis toxin and filamentous hemagglutinin.

A novel process for preparing non-pyrogenic toxoids of pertussis toxin (PT) and filamentous hemagglutinin (FHA) is described. The process consists of chromatographies on perlite then on hydroxylapatite. Purification yields for PT and FHA are 62 and 68%, respectively. The purification process takes advantage of the novel use of perlite (a filter aid) for the simultaneous purification of PT and FHA. The hydroxylapatite, in addition to removing the remaining contaminants, also concentrates the antigens. The resulting PT and FHA are approximately 95% pure, and are non-pyrogenic as judged by the rabbit pyrogen test. The purification process is simple, inexpensive, and does not use blood components or toxic substances. The mild conditions in which the PT and FHA are purified ensure the recovery of native protein. The purified PT and FHA are detoxified in the presence of glycerol using glutaraldehyde and formaldehyde, respectively, to produce antigenic components of an acellular pertussis vaccine. The final PT and FHA toxoids are immunogenic in guinea-pigs and have been shown to be protective in the mouse intracerebral challenge test.

Bordetella pertussis↗
PubMed1991

Viral serology after bone marrow transplantation.

Bone marrow transplantation (BMT) may change the recipient's pretransplant serostatus for herpes group viruses. We reviewed 68 patient records (1 year's transplants) to determine how frequently this occurs. Only 7 had data on serostatus before as well as at days 20 to 35 and greater than 100 after BMT. Serostatus was assessed by complement fixation and ELISA. All patients received a variety of blood-product support after BMT. One patient converted from anti-varicella zoster virus (VZV) positive to negative after BMT and developed clinical chickenpox; an additional patient converted from anti-VZV negative to positive after BMT but reverted to seronegative by day 102. One patient converted from anti-cytomegalovirus (CMV) positive pre-BMT to persistently anti-CMV negative post-BMT (donor: anti-CMV negative). Two patients had a greater than 4-fold fall in anti-herpes simplex (HSV) antibody post-BMT, and both shed HSV after BMT. Most seronegative recipients of marrow from seropositive donors developed herpesvirus antibodies. We conclude that the herpesvirus serostatus of BMT recipients should be determined again after BMT to aid in decisions about antiviral prophylaxis and diagnosis of clinical disease.

Adult↗