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Biomedical subjects

A McKnight

Publications and source records attributed to A McKnight.

At least 55 records · Page 3Linked to original sources
PubMed1992

Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4.

We describe human immunodeficiency type 2 (HIV-2) strains which induce cell-to-cell fusion and infect certain CD4- human cell lines. Soluble CD4 (sCD4) induces or enhances fusion by most HIV-2 strains tested. Soluble CD4-immunoglobulin G chimeras and conjugates of sCD4 and antibody to the third domain of CD4 block HIV-2 fusion of CD4- cells. We conclude that HIV-2 can enter CD4- cells via an alternative cell surface receptor to CD4. While some strains entered efficiently, others retained a dependency on an interaction with sCD4 to initiate changes in the virion envelope required for membrane fusion.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Continuing medical education for general practitioners--a Northern Ireland plan.

Following the introduction of the 1990 contract for general practitioners and the new postgraduate education allowance, the Northern Ireland Continuing Medical Education Group, comprising the clinical tutors from four Belfast hospitals and members of the University department of general practice, was established to provide high quality co-ordinated continuing medical education for general practitioners. A questionnaire was sent to all general practitioners in Northern Ireland to find out their needs and preferences with regard to continuing education. The responses indicate the value of small group discussion as well as the traditional lecture and the important role of local hospital consultants in providing education. Therapeutics, recent advances in medicine and learning new skills are all desirable topics. The group intends to use this information in the provision of courses for general practitioners in the province.

Education, Medical, Continuing↗
PubMed1991

Studies on the immunogenicity of Chinese hamster ovary cell-derived recombinant gp120 (HIV-1IIIB).

Recombinant DNA-derived gp120 (HIV-1IIIB) expressed in chinese hamster ovary cells elicited specific humoral and cell-mediated immune responses in a variety of mammals. Antisera from immunized rabbits, sheep and goats recognized virus-derived gp120 and its precursor (gp160). Neutralizing antibodies were also elicited, but only in a few animals, and this may be related to the protein's susceptibility to cleavage through the neutralizing domain. However, in rabbits the degree of cleavage of gp120 had little or no effect on its antigenicity or immunogenicity. All antisera had limited cross-reactivity to envelope glycoproteins from a panel of HIV-1 isolates suggesting that immunodominant antibody epitopes are in variable regions of the recombinant gp120. Antigen-specific T-cell responses were detected in immunized macaques and were found to be stronger and more prolonged when gp120 was administered in Freund's adjuvant rather than alum.

Animals↗
PubMed1991

Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization.

Several parameters which may affect the infectivity of human immunodeficiency virus type 1 in tissue culture were analyzed. In particular, we used gel exclusion chromatography to investigate how the loss of the surface glycoprotein gp120 from virions of the HTLV-IIIB (IIIB), HTLV-IIIRF (RF), and SF-2 isolates modulates infectivity. In IIIB and RF cultures, a high proportion of the total gp120 was virion bound initially but was gradually lost from the virions over time. In contrast, most of the gp120 (and p24) in SF-2-infected cultures was soluble and the few particles present had a fivefold-lower level of virus-bound gp120. However, this reduced level of virion-bound gp120 was more resistant to shedding. Loss of a major proportion of gp120 from IIIB and RF virions resulted in reduced infectivities, and in addition, the resulting accumulation of soluble gp120 in the cultures could competitively inhibit viral infection, especially with SF-2. Increased shedding of virion gp120 also affected the neutralization of IIIB and RF particles. However, the high sensitivity to human serum neutralization characteristic of SF-2 was unaffected by soluble gp120 in cultures, suggesting that the epitopes responsible are not present on soluble gp120.

Amino Acid Sequence↗
PubMed1990

Role of pyloroplasty in the retrosternal stomach: results of a prospective, randomized, controlled trial.

A prospective, randomized, controlled trial comparing clinical outcome and emptying of a solid meal from the retrosternal stomach, with and without pyloroplasty is described. Forty consecutive patients with oesophageal cancer undergoing retrosternal gastric reconstruction of the oesophagus were studied. In 20 patients the pylorus was left intact (group 1) and 20 patients underwent an Aust pyloroplasty (group 2). Nine patients in group 1 suffered postoperative symptoms of gastric stasis compared with only one patient in group 2 (P = 0.0106). Three patients in group 1 died from aspiration pneumonia before discharge from hospital. A gastric emptying test was performed on 24 patients between 1 and 3 months after surgery. By this time, most survivors had recovered from symptoms attributed to gastric stasis and no significant difference in gastric emptying could be demonstrated between the two groups. Selection of patients, a wide range of emptying times and improvement in gastric emptying on follow-up may explain the lack of correlation between postoperative symptomatology and the gastric half-emptying times. A pyloroplasty is advised to prevent the potentially lethal effects of gastric stasis in the early postoperative period following retrosternal reconstruction of the oesophagus.

Adult↗
PubMed1990

HIV-1 neutralizing monoclonal antibodies induced by a synthetic peptide.

We have developed a series of murine monoclonal antibodies to a region of the 120 kD envelope glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1). This region has previously been implicated as a site for virus neutralization by antisera raised to recombinant proteins and by antibodies made to full-length gp120 purified from virus. The antigen employed was a synthetic peptide containing 15 amino acids, representing amino acid residues 308-322, RIQRGPGRAFVTIGK, of env gp120 (HTLV-IIIB isolate). Five of the monoclonal antibodies raised to this antigen have reactivity with gp120 from divergent strains of HIV-1 in Western blot assays. The two of these five which were tested with live cells infected with the divergent HIV-1 isolates IIIB, MN, and RF were specifically reactive by fluorescence analyses with cells infected with the MN and IIIB isolates. Four of the five monoclonal antibodies blocked the fusion of IIIB-infected cells with uninfected MOLT-4 target cells. The monoclonal antibody most reactive with MN-infected cells by fluorescence, #5025A, blocked the fusion of MN-infected cells with uninfected MOLT-4 cells. Four of the five monoclonal antibodies neutralized the IIIB isolate of HIV-1 in vitro, but none neutralized the MN or RF isolates at the levels of antibody tested (less than or equal to 50 micrograms/ml). Taken together these data indicate that monoclonal antibodies to the immunodominant neutralizing domain of HIV-1 gp120 display different levels of group reactivity depending on the assay system being examined.

Amino Acid Sequence↗
PubMed1990

Localization of the receptor gene for type D simian retroviruses on human chromosome 19.

Simian retrovirus (SRV) serotypes 1 to 5 are exogenous type D viruses causing immune suppression in macaque monkeys. These viruses exhibit receptor interference with each other, with two endogenous type D viruses of the langur (PO-1-Lu) and squirrel monkey, and with two type C retroviruses, feline endogenous virus (RD114/CCC) and baboon endogenous virus (BaEV), indicating that each utilizes the same cell surface receptor (M. A. Sommerfelt and R. A. Weiss, Virology 176:58-69, 1990). Vesicular stomatitis virus pseudotype particles bearing envelope glycoproteins of RD114, BaEV, and the seven SRV strains were employed to detect receptors expressed in human-rodent somatic cell hybrids segregating human chromosomes. The only human chromosome common to all the susceptible hybrids was chromosome 19. By using hybrids retaining different fragments of chromosome 19, a provisional subchromosomal localization of the receptor gene was made to 19q13.1-13.2. Antibodies previously reported to be specific to a BaEV receptor (L. Thiry, J. Cogniaux-Leclerc, R. Olislager, S. Sprecher-Goldberger, and P. Burkens, J. Virol. 48:697-708, 1983) did not block BaEV, RD114, or SRV pseudotypes or syncytia. Antibodies to known surface markers determined by genes mapped to chromosome 19 did not block virus-receptor interaction. The identity of the receptor remains to be determined.

Animals↗
PubMed1989

The role of membranous obstruction of the inferior vena cava in the etiology of hepatocellular carcinoma in Southern African blacks.

Membranous obstruction of the inferior vena cava has been incriminated as a risk factor for hepatocellular carcinoma in South African Blacks and in Japanese. However, the frequency with which this anomaly is found in patients with hepatocellular carcinoma, and hence its numerical importance as an etiological association of the tumor, has not been ascertained. Using radionuclide and contrast venography as well as necropsy and laparotomy examination, we investigated 162 unselected southern African Blacks with hepatocellular carcinoma together with appropriate controls for the presence of membranous obstruction of the inferior vena cava. Membranous obstruction of the inferior vena cava was detected in six of 162 (3.7%) hepatocellular carcinoma patients, compared with one of 279 subjects (0.36% p = 0.011) dying a violent death, none of 55 patients (p = 0.169) with malignant disease other than hepatocellular carcinoma and eight of 150 patients (5.3%; p = 0.336) being investigated for conditions which might have been associated with membranous obstruction of the inferior vena cava. Six of the 15 individuals (40%) found to have membranous obstruction of the inferior vena cava had concomitant hepatocellular carcinoma, confirming that membranous obstruction of the inferior vena cava constitutes a risk factor for the development of the tumor. However, only a very small proportion of hepatocellular carcinoma patients have this abnormality, so that it is a minor causal association of the tumor only.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1989

The role of carbohydrate antigen 19-9 as a tumour marker of oesophageal cancer.

Carcinoma of the oesophagus is endemic in certain well demarcated areas throughout the world, and a method of screening population groups at high risk for oesophageal cancer is urgently needed. In this study the sensitivity and specificity of the carbohydrate antigen CA19-9 as a marker of carcinoma of the oesophagus in African patients was examined. The normal range was established by assay of serum samples from healthy black blood donors, using a solid phase radioimmunoassay with mouse monoclonal antibody to CA19-9 labelled with 125I. Serum concentrations of CA19-9 were then measured in 100 African patients with oesophageal cancer and 28 patients with benign oesophageal disease. The upper limit of CA19-9 in the normal controls was 40 U ml-1. Thirty-four patients with oesophageal cancer and five with benign oesophageal disease had elevated levels. Therefore, in this series, the sensitivity of CA19-9 as a marker of oesophageal cancer was 34% and the specificity was 82%. While CA19-9 is not sufficiently sensitive to be used as a screening test of oesophageal cancer, it compares favourably with other known tumour markers of this disease, and may have a role in monitoring disease recurrence and response to treatment.

Adult↗
PubMed1989

Evaluation of human and simian immunodeficiency virus plaque and neutralization assays.

A number of CD4+ T cell lines were compared for their ability to act as target cells for human immunodeficiency virus (HIV) infection in syncytium- and plaque-forming assays. MT-4 and C8166 cells were the most sensitive indicator cells for HIV- and simian immunodeficiency virus (SIV)-induced cytopathic effects, and gave rise to macroscopic (MT-4) and microscopic (C8166) plaques. The MT-4 plaque assay was evaluated for the measurement of HIV- and SIV-neutralizing antibodies.

Animals↗
PubMed1988

Human immunodeficiency viruses: neutralization and receptors.

The envelope glycoproteins of HIV, gp120 and gp41, contain epitopes recognized by neutralizing antibodies. Studies of human sera from infected individuals indicate that group-specific neutralization antigens common to most isolates of HIV-1 exist, and that some HIV-2 antisera cross-neutralize HIV-1. Neutralization epitopes for HIV-1 have been identified and mapped, including a group-specific antigen on gp41, and a type-specific antigen on gp120. Neutralization "escape" mutants have been selected in vitro with a neutralizing mab to the type-specific antigenic loop. The CD4 antigen binds HIV-1 gp120 with high affinity and acts as the receptor on human and simian T-lymphocytes and monocytes for all strains of HIV-1, HIV-2, and SIV tested. Following binding to the CD4 receptor, HIV becomes internalized by a pH-independent process. The principle binding domain for gp120 is located in the N-terminal V domain of CD4. Anti-idiotypic sera to CD4 mabs recognizing the same site weakly neutralize HIVs of many strains, and soluble, recombinant forms of CD4 strongly neutralize HIV. Neither anti-CD4 mabs nor sCD4 inhibit the low level of plating of HIV observed on tumour cells in culture of glial (brain) and muscle origin, indicating that CD4 is not essential for infection of these cell types.

Animals↗
PubMed1988

The use of radionuclide venography in the differential diagnosis of inferior vena caval obstruction.

In using radionuclide imaging of the inferior vena cava (RIVC) to investigate the prevalence of membranous obstruction of the inferior vena cava (IVC) in patients with hepatocellular carcinoma, it was necessary first to determine if this technique would distinguish membranous obstruction of the IVC both from other causes of IVC obstruction likely to be encountered in these patients and from the picture obtained with severe ascites. RIVC readily distinguished an obstructed from a normally patent IVC. However, membranous obstruction of the IVC could not in most instances be differentiated from extrinsic compression of the IVC by an enlarged tumourous liver, occlusion of the lumen of the IVC by tumour, or the effect of severe ascites. In a proportion of the patients with membranous obstruction of the IVC, flow of the radionuclide through large superficial collateral vessels was seen, enabling this diagnosis to be made with confidence. Thus, if RIVC shows the IVC to be obstructed or if severe ascites is present, contrast venography will usually be necessary to determine the nature of the obstructing lesion.

Ascites↗
PubMed1987

Synthesis and characterization of all four isomers of the muscarinic agonist 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane].

The four separated isomers of the muscarinic agonist 1, previously known as AF30, have been synthesized by a route that has allowed the absolute stereochemistry of each isomer to be assigned. With the chirality of (-)-camphanic acid known, X-ray analysis of the more crystalline intermediate diastereomeric camphanate 5A allowed the absolute stereochemistry at the quinuclidine chiral center to be determined. Each diastereomer was separately transformed into the spirodioxolane with concomitant introduction of the second chiral center. Chromatographic separation followed by a second crystal structure determination revealed the absolute stereochemistry of all four isomers of 1. Detailed biological evaluation of each isomer indicated that while the 3(R),2'(S) isomer was the most active in binding studies, it was the 3(R),2'(R) isomer that displayed the largest functional selectivity between ganglion (M-1 site) and heart (M-2 site). With the same internal chiral standard, the absolute configuration of the more active enantiomer of 3 was shown to be S, confirming earlier literature reports.

Animals↗
PubMed1987

Antenatal care in Belfast.

A questionnaire study of mothers' views of the antenatal care provided in Belfast showed general satisfaction. Retrospective examination of their charts however showed in some cases that insufficient attention was paid to the medical and obstetric history in the selection of type of care made by the women and their doctors. Some women with high risk factors were booked for shared care and some patients at low risk were booked for total hospital care. The reasons for this are unclear.The mothers felt that continuity of care and communication at the health centre were better than at the hospital. Analysis of the number of hospital attendances showed that shared care patients appeared to be making an excessive number of visits to hospital. Many total hospital care patients also admitted that they were attending their general practitioners. There appeared to be marked duplication of effort as a result of poor communication between patient, general practitioner and hospital.Alternative ideas for care are suggested - a more integrated system for sharing antenatal care, and the development of general practitioner units within the specialist obstetric hospital.

Attitude↗
PubMed1987

Alcohol consumption in pregnancy--a health education problem.

The drinking habits, demographic characteristics and knowledge about the effects of drinking during pregnancy of 380 pregnant women in Belfast were investigated. Forty-five per cent of the women were non-drinkers, 39% were occasional drinkers and 16% were regular drinkers. The majority of women knew that alcohol could harm their babies but were unsure of the specific effects. Regular drinkers were more likely than occasional drinkers or non-drinkers to say that harm would only be done if alcohol was taken in excess. The topic of alcohol is rarely discussed at antenatal clinics and cases of fetal alcohol syndrome, an uncommon but preventable condition, are probably being missed as a result. There is a need for more health education for the general public, especially school children, and for increased awareness among health professionals that the problem of alcohol in pregnancy exists and is likely to increase if the trend towards alcohol abuse among the younger members of the population continues.

Alcohol Drinking↗
PubMed1986

Availability and acceptance of health education among socially 'at risk' pregnant women attending health centres in Belfast.

This study highlights the large number of pregnant women in Belfast who fall into the 'at risk' category based on socioeconomic factors and suggests a need for greater emphasis on health education by professionals in both the fields of health and education in order to improve the knowledge and change the attitudes and behaviour of pregnant women; this could play an important part in reducing infant mortality and handicap in our society. The study showed that neither patients nor health care teams see health education as an integral part of antenatal and postnatal care and that little impact has been made in encouraging patients to plan their pregnancies, stop smoking and eat a more balanced diet.

Adolescent↗