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Biomedical subjects

H Harris

Publications and source records attributed to H Harris.

At least 19 recordsLinked to original sources
PubMed2003

Measuring and visualizing single molecular interactions in biology.

In recent years, considerable attention has focused upon the biological applications of the atomic force microscope (AFM), and in particular in its ability to explore biomolecular interaction events at the single molecule level. Such measurements can provide considerable advantages, as they remove the data averaging inherent in other biophysical/biochemical approaches that record measurements over large ensembles of molecules. To this end AFM has been used for both the high-resolution imaging of a range of individual biological molecules and their complexes, and to record interaction forces between single interacting molecules. In a recently initiated project we have begun to utilize these approaches to explore the interactions of a range of biologically important peptides with model and cell membrane surfaces. In this review, the potential value of AFM for the investigation of a range of biomolecular interaction events will be discussed, but highlighting in particular its potential for the study of interactions of peptides/proteins with biological membranes.

Animals↗
PubMed2002

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.

Blood Transfusion↗
PubMed2001

Coordination and dehydrogenation of PH(3) by 23 transition metal ions in the gas phase: FTICR experiments and density functional interpretations.

The reactions of 23 transition metal ions M+(g) with phosphane (PH(3)) have been investigated using Fourier transform ion cyclotron resonance spectrometry. Two main reaction pathways are observed, sequential dehydrogenation of multiple (up to nine) phosphane molecules, and addition of multiple (up to four) phosphane molecules. The addition and dehydrogenation reaction pathways are, for the most part, mutually exclusive for a particular metal. Dehydrogenation of phosphane is observed for metal ions toward the lower left of the transition block, and the addition process is predominant toward the top right. The dehydrogenation process is considerably faster than the addition, and sequentially produces the species MPH+, MP(2)(+), MP(3)H(+), MP(4)(+), etc. Density functional calculations were used to evaluate collision trajectories, reaction mechanisms, structures of intermediates (including a number of MoP(x)H(y)(+) species), and to identify the factors determining whether each metal reacts by dehydrogenation or addition. Insertion of M+ into P-H bonds is calculated to be a barrierless, exergonic process for only those metals which are observed to dehydrogenate phosphane molecules. A reaction mechanism involving the transfer of H atoms from P to M followed by the elimination of H(2) from M is profiled for Ru. The energetic origins of the metal influence on reaction type have been traced to the energy changes for the first stage migration of H from P to M. These experimental and theoretical results should be valuable in applications where PH(3(g)) is used in the generation of bulk and surface materials involving metal phosphides.

Journal Article↗
PubMed2001

Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation.

Incubation of rat aortas with endotoxin and interferon-gamma for 24 h resulted in an aortic oxygen consumption that was substantially inhibited and strongly oxygen dependent (37% inhibition at 160 microM O(2) and 62% inhibition at 80 microM O(2) relative to untreated aortas). This respiratory inhibition was reversed by a nitric oxide (NO) scavenger (oxyhemoglobin) or by an inhibitor of inducible NO synthase [N-(3-(aminomethyl)benzyl)acetamide x 2HCl, 1400W], but not by an inhibitor of soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one). Addition of 1 microM NO to untreated aortas caused rapid and reversible inhibition of oxygen consumption that was greater at lower oxygen concentrations. Incubation of endothelial cells isolated from rat aortas with endotoxin and interferon-gamma for 24 h resulted in a steady-state NO concentration of approximately 0.5 microM and 90% inhibition of cellular oxygen consumption that was immediately reversed by an NO scavenger (oxyhemoglobin). These results suggest that during inflammation and sepsis, tissue respiration may be substantially reduced due to inhibition by NO of cytochrome oxidase.

Amidines↗
PubMed2001

Regulation of metallothionein II messenger ribonucleic acid measures exogenous estrogen receptor-beta activity in SAOS-2 and LNCaPLN3 cells.

Estrogen receptor-beta (ERbeta) is a recently discovered member of the steroid hormone superfamily. Because its distribution is distinct from that of the classical estrogen receptor, and it is expressed in several nonclassical estrogen target tissues (e.g. prostate and bladder), its role in mediating the action of estrogen is unclear. One approach to elucidating the function of this receptor is to identify genes that it regulates. Using differential display, we profiled the messenger RNAs regulated by 17beta-estradiol in SAOS-2 and LNCaPLN3 cells overexpressing ERbeta. Follow-up studies used cells expressing either ERalpha or ERbeta. One gene, metallothionein II, was regulated by both receptor subtypes in LNCaPLN3 cells, but only by ERbeta in SAOS-2 cells. Because cycloheximide blocks this response, induction is probably mediated through regulation of at least one other protein. Identification of endogenous genes that are regulated differentially by ERalpha and ERbeta will be valuable tools in elucidating the function of ERbeta and the mechanisms by which these two receptors regulate transcription.

Cycloheximide↗
PubMed2000

Active surveillance of hepatitis C infection in the UK and Ireland.

AIM: To investigate the prevalence, distribution, and clinical details of paediatric hepatitis C virus (HCV) infection in the UK and Ireland. METHODS: Active monthly surveillance questionnaire study coordinated through the British Paediatric Surveillance Unit, to all consultant paediatricians in 1997 and 1998. RESULTS: A total of 182 HCV infected children were reported from 54 centres and by paediatricians from eight different specialties. In 40 children HCV was acquired through mother to child transmission (MTC children); 142 were infected by contaminated blood products (n = 134), organ transplantation (n = 2), needles (n = 4), or unknown risk factor (n = 2). Intravenous drug use was the risk factor for 35 mothers of MTC children. Twelve children were coinfected with HIV and four with HBV. Recent serum aspartate aminotransferase or alanine aminotransferase values were at least twofold greater than the upper limit of normal in 24 of 152 children; this occurred in five of 11 HIV coinfected children. Liver histology, available in 53 children, showed normal (7%), mild (74%), moderate (17%), or severe (2%) hepatitis. Twenty eight children had received therapy with interferon alfa. CONCLUSION: Most current paediatric HCV infection in UK and Ireland has been acquired from contaminated blood products, and most children are asymptomatic. There is a need for multicentre trials to inform clinical practice and development of good practice guidelines in this area. Long term follow up of this cohort of HCV infected children is planned to help determine the natural history over the long term of HCV acquired during infancy and childhood.

Child↗
PubMed2000

Sources of infection among persons with acute hepatitis A and no identified risk factors during a sustained community-wide outbreak.

CONTEXT: Hepatitis A is a common vaccine-preventable disease in the United States. Most cases occur during community-wide outbreaks, which can be difficult to control. Many case-patients have no identified source. OBJECTIVE: To identify foodborne and household sources of hepatitis A during a community-wide outbreak. DESIGN: Serologic and descriptive survey. SETTING: Salt Lake County, Utah. PARTICIPANTS: A total of 355 household contacts of 170 persons reported with hepatitis A during May 1996 to December 1996, who had no identified source of infection; and 730 food handlers working in establishments where case-patients had eaten. MAIN OUTCOME MEASURE: Prevalence of immunoglobulin M antibodies to hepatitis A virus (IgM anti-HAV) among household and food service contacts. RESULTS: Overall, 70 household contacts (20%) were IgM anti-HAV-positive, including 52% of children 3 to 5 years old and 30% of children <3 years old. In multivariate analysis, the presence of a child <3 years old (odds ratio [OR]: 8.8; 95% confidence limit [CL]: 2.1,36) and a delay of >/=14 days between illness onset and reporting (OR: 7. 9; 95% CL: 1.7,38) were associated with household transmission. Of 18 clusters of infections linked by transmission between households, 13 (72%) involved unrecognized infection among children <6 years old. No food handlers were IgM anti-HAV-positive. CONCLUSION: During a community-wide outbreak, HAV infection among children was common, was frequently unrecognized, and may have been an important source of transmission within and between households. Transmission from commercial food establishments was uncommon. Ongoing vaccination of children may prevent future outbreaks.

Acute Disease↗
PubMed2000

The implementation of the HOT program at the Royal Women's Hospital.

At the Royal Women's Hospital from November 1995, mothers and their infants were discharged on day three (a three-night stay) following a normal vaginal birth, if they were considered to be well and coping with early postnatal life. However, by March 1996, there were indications that not all mothers were managing breastfeeding as well as they needed to after discharge home. In an effort to reduce early avoidable breastfeeding problems, an extensive re-education program was undertaken. The 'Hands-Off Technique' Program (HOT) aimed to address the problem by educating the midwifery staff on ways to teach mothers about correct positioning and self-attachment of their babies without actually doing it for them.

Australia↗
PubMed1999

National Confidential Enquiry into counselling for genetic disorders by non-geneticists: general recommendations and specific standards for improving care.

OBJECTIVES: To assess genetic counselling by non-geneticists and to improve clinical practice. DESIGN: National retrospective review of casenotes. SETTING: Antenatal, paediatric, medical, and surgical units. SAMPLE: 1293 genetic events were identified, involving potentially avoidable cases of Down's syndrome, neural tube defect, cystic fibrosis, beta thalassaemia major and late onset medullary carcinoma of the thyroid (multiple endocrine neoplasia). Notes were available for review in 888 (69%) of these cases. OUTCOMES: Documented counselling, offers of relevant genetic screening and prenatal diagnosis. RESULTS: Clinical audit was frustrated by poor quality hospital records lacking evidence of counselling. Non-geneticist clinicians concentrate on the management of disease, and may overlook the need for counselling and recording data which patients will later need for decisions about reproduction or disease prevention. Counselling, screening and prenatal diagnosis were sometimes impossible because of late booking in pregnancy, or because of delayed diagnosis of an earlier affected child with cystic fibrosis. There are marked regional inequalities of access to genetic services, particularly for minority ethnic groups with increased risks of thalassaemia. Although patients were selected for this enquiry because they had known high risks of genetic disorders, on average less than half were referred to medical geneticists. General recommendations relevant for improvement of care for patients and families with medical genetic needs and those specific for each disorder are given. CONCLUSIONS: Assessment of the quality of genetic care becomes increasingly important as genetic counselling spreads beyond the narrow confines of specialist genetic services. Even though the events studied in this enquiry largely occurred between 1991 and 1995, there is little reason to believe that clinicians in general have become markedly better trained in medical genetics. The General Medical Council and Medical Royal Colleges should urgently consider the need for a national policy for improving undergraduate and postgraduate medical, nursing and midwifery education in genetics. Commissioners of clinical services should require that genetic management be at least as well-documented as surgical operations, drug records and informed consent, perhaps by using a nationally agreed pro-forma for prenatal diagnosis. Regular audit of counselling provided by non-geneticists is necessary to confirm that clinical improvements are occurring and standards are being met. The Confidential Enquiry provides data for a systematic approach to clinical governance of genetics in all specialities. This sets the scene for multi-speciality NHS genetic services capable of giving patients greater consistency both in access and in quality.

Clinical Competence↗
PubMed1999

In vitro evaluation methods for Clostridium botulinum type C and D vaccines.

Reagents were prepared for use in ELISAs to determine the concentration of the antigenic components of Clostridium botulinum type C and D. The results obtained were compared with the L+dose assay and a good correlation was found between the two assays for measurement of the C and D neurotoxin concentration. These ELISAs were also used to determine the concentration of the neurotoxins in toxoid form. The relationship between the C neurotoxin dose, in toxoid form, and the immune response in guinea pigs could be deduced from the data obtained. The relationship for the D neurotoxin was not that clear, as the same concentration of the antigen resulted in variable potency values. However, these ELISAs can be used to formulate the concentration of the C and D components in the final bivalent vaccine. Replacement of the preliminary potency assay on the monovalent components after production with the in vitro assays will shorten the total production time of the vaccine by about 60 days. The economical and ethical implications are the reduction in the use of animals to evaluate the vaccine.

Animals↗
PubMed1999

Knowledge about medical genetics in health care.

Effective genetic services depend upon co-operation between medical geneticists and many different non-geneticist professionals to ensure that the most appropriate patients are referred to geneticists and that those that require long-term care receive it. Important determinants of the quality of genetic services are the knowledge that professionals have about clinical genetics and the equitable distribution of adequately resourced genetic centres. Consequently, we have investigated in a European context how much clinically relevant genetics non-geneticists know, how competent non-geneticists are in counselling their own patients, how well equipped specialist genetic centres are, who refers to genetic centres and what they refer and who offers continuing care to patients and families whose problems are not resolvable at a limited genetic clinic visit.

Journal Article↗
PubMed1999

An audit of mastitis in the emergency department.

A medical audit was conducted in 1997 of hospital records of women attending the emergency department of the Royal Women's Hospital in Melbourne, Australia, in 1996 with a diagnosis of "mastitis." One hundred and seven women were diagnosed with mastitis; approximately half were primiparous (53%) and the median age of the baby was 14 days. Most women (69%) attended the emergency department after normal working hours. Thirty-nine percent of the women were afebrile, and only 27% had a temperature of 38.5C or higher. The majority of women were prescribed flucloxacillin. Milk culture was obtained in only 15 cases, and Staphylococcus aureus was the most common pathogen.

Adolescent↗
PubMed1999

A collection method and high-sensitivity enzyme immunoassay for sweat pyridinoline and deoxypyridinoline cross-links.

BACKGROUND: Collagen cross-link molecules such as pyridinoline (PYD), deoxypyridinoline (DPD), and N-terminal cross-linked peptides (NTX) have been measured in urine as indices of bone resorption. However, very little is known regarding the excretion of pyridinolines into other biological fluids. We report a collection device, normalizing analyte, and high-sensitivity immunoassay for quantitative analysis of free pyridinoline cross-links in sweat. METHODS: Flame atomic emission and ion-selective electrode techniques were used to measure potassium as a sweat volume marker. The Pyrilinks immunoassay for urine free pyridinolines was optimized to increase sensitivity for measurements in sweat. The precision, accuracy, and detection limit of this assay were characterized. To assess values and variability of sweat pyridinolines in human subjects, a nonocclusive skin patch was used to collect sweat samples from a reference group and from a mixed group experiencing accelerated bone resorption, postmenopausal women and men receiving gonadotropin-releasing hormone for prostate cancer. RESULTS: The immunoassay intra- and interassay variations were </=10% and <16%, respectively, with a detection limit of 309 pmol/L. Linearity upon dilution and analytical recovery ranged from 93% to 109% and 85% to 122%, respectively. Sweat PYD values normalized to potassium output yielded a weekly intraindividual biological variability of 14.7%. The mean increase in the population experiencing increased bone resorption vs the reference group was 36% (P <0.05) for sweat PYD/K vs 23-40% (P <0.05) for urinary PYD/Cr, DPD/Cr, and NTX/Cr. CONCLUSION: We conclude that this new platform sweat collection technology and PYD immunoassay show potential as an indicator of bone resorption.

Amino Acids↗