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Biomedical subjects

J Findlay

Publications and source records attributed to J Findlay.

At least 19 recordsLinked to original sources
PubMed1999

Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110.

Examination of cells at the early stages of herpes simplex virus type 1 infection revealed that the viral immediate-early protein Vmw110 (also known as ICP0) formed discrete punctate accumulations associated with centromeres in both mitotic and interphase cells. The RING finger domain of Vmw110 (but not the C-terminal region) was essential for its localization at centromeres, thus distinguishing the Vmw110 sequences required for centromere association from those required for its localization at other discrete nuclear structures known as ND10, promyelocytic leukaemia (PML) bodies or PODs. We have shown recently that Vmw110 can induce the proteasome-dependent loss of several cellular proteins, including a number of probable SUMO-1-conjugated isoforms of PML, and this results in the disruption of ND10. In this study, we found some striking similarities between the interactions of Vmw110 with ND10 and centromeres. Specifically, centromeric protein CENP-C was lost from centromeres during virus infection in a Vmw110- and proteasome-dependent manner, causing substantial ultrastructural changes in the kinetochore. In consequence, dividing cells either became stalled in mitosis or underwent an unusual cytokinesis resulting in daughter cells with many micronuclei. These results emphasize the importance of CENP-C for mitotic progression and suggest that Vmw110 may be interfering with biochemical mechanisms which are relevant to both centromeres and ND10.

Animals↗
PubMed1998

Active vision: visual activity in everyday life.

Recent studies that consider how vision is used in everyday life have led to a new perspective in visual science, in which more emphasis is placed on the active role of the viewer.

Fixation, Ocular↗
PubMed1998

Immunoelectron microscopic localisation of the OMP90 family on the outer membrane surface of Chlamydia psittaci.

The putative outer membrane location of the OMP90 (formerly POMP) family from the ovine abortion strain of Chlamydia psittaci was investigated by immunoelectron microscopy. Using a non-embedding technique, antigens were shown to be localised on the outer membrane surface of both elementary and reticulate bodies, the infectious and non-infectious forms of Chlamydiae respectively. Antibodies affinity-purified against the expressed amino- and carboxy-terminal halves of one of the family members. OMP90A, demonstrated that the amino half is surface-exposed while the carboxyl half is most probably localised internally. Surface localisation on elementary bodies indicates the importance of these proteins as protective antigen candidates.

Abortion, Veterinary↗
PubMed1990

Long term survival after intensive care.

OBJECTIVE: To examine the long term survival of critically ill patients admitted to an intensive therapy unit and to ascertain the effects of age, severity of illness, and diagnostic category at admission on survival. DESIGN: Retrospective observational study with prospectively gathered data on all patients admitted to the unit between June 1985 and July 1987 and followed up until 1 January 1989. SETTING: Regional intensive therapy unit. PATIENTS: 513 critically ill adult patients, 16 of whom were excluded because measurements on severity of illness scoring were not available. MAIN OUTCOME MEASURES: Age, severity of illness (determined with the acute physiology and chronic health evaluation (APACHE) II score), and diagnostic category on admission; deaths in the unit; and long term survival after discharge. Details of the survivors were sent to the Registrar General for Scotland, who issued copies of death certificates for the patients who had died between discharge and 1 January 1989. RESULTS: Of 497 patients, 119 (24%) died in the intensive therapy unit and 120 (24%) after discharge, leaving 258 (52%) who were still alive at two years. The median (APACHE II) score was 13 and about half of the patients were aged 55 years or more. A wide range of critical illnesses, except neurosurgical emergencies, were treated. Survival analysis showed that only 41 (34%) of 122 patients with an APACHE II score of greater than or equal to 20 were alive at one year (95% confidence interval 25 to 42) compared with 124 (80%) of 155 patients with a score of less than 10 (73 to 87). Of the 144 patients aged 65 or more, only 68 (47%) survived to one year (39 to 55) but 90 (83%) of the 109 patients aged between 18 and 34 survived a similar period (76 to 71). Mortality was also related to diagnostic category; 71% of trauma victims survived to one year compared with only 41% of those admitted with gastrointestinal pathology. Univariate analysis of the results showed that age, severity of illness, and diagnosis were all predictors of long term survival. Multivariate analysis, however, showed that only age and severity of illness were independent prognostic factors. CONCLUSIONS: Long term survival of patients treated in an intensive therapy unit is related to severity of illness and to age. The outcome from critical illness in the elderly population is poor.

Adolescent↗
PubMed1990

Interleukin-6 enhances the induction of human lymphokine-activated killer cells.

Human peripheral blood mononuclear cells develop a powerful lytic capacity when cultured in vitro with interleukin-2 (IL-2), becoming lymphokine-activated killer cells (LAK cells). As part of an investigation into means of influencing this process, the effect of other cytokines has been examined. In this study we describe the ability of interleukin-6 (IL-6) to regulate the induction and function of human LAK cells. The results show that substitution of IL-6 for IL-2 did not lead to the development of functional LAK cells, nor was IL-6 able to alter the lytic capacity of established LAK cells. However, when IL-6 was included with IL-2 during the induction phase of the LAK cells, the resulting cells displayed considerably greater lytic activity than those prepared with IL-2 alone. This effect was IL-6 dose-related. These results indicate that LAK cell development may be positively regulated in vitro; the implications of this observation for the clinical usage of LAK cells are discussed.

Cells, Cultured↗
PubMed1990

Three-dimensional modelling of G protein-linked receptors.

Members of the G protein-linked receptor superfamily have not yet yielded to X-ray crystallography. However, diffraction data from other membrane-bound receptors - the photosynthetic reaction centre and bacteriorhodopsin - have provided some information that may also apply to the G protein family. John Findlay and Elias Eliopoulos integrate this information together with analysis of amino acid sequences from cloned receptors, to derive workable three-dimensional models of these proteins. Such models identify ligand-binding and G protein-associating domains.

Animals↗
PubMed1990

Survival associated with renovascular disease in Glasgow and Newcastle: a collaborative study.

Data from 121 consecutive patients with hypertension and renovascular disease, first diagnosed between 1975 and 1982 in Glasgow and Newcastle, were analysed retrospectively to determine the factors which influenced their outcome. Thirty-six patients died between the data of arteriography and 1st January 1987, giving five and ten year survival rates of 83% and 67%. Survival was greatly reduced in comparison with that of age-sex-matched controls in the general population of the West of Scotland, and was also less than that of essential hypertensives matched for age, sex, initial diastolic blood pressure and smoking habit who had attended the Glasgow Blood Pressure Clinic during the same period. Multivariate analysis showed that age, cigarette smoking and presence of atheromatous disease were significantly and independently related to outcome among the patients with renovascular disease, whereas male sex, centre of origin, severity of hypertension when first seen, initial renal function and presence of bilateral disease were not. Despite a trend towards benefit from surgical intervention (ten year survival in medical group 62%, in surgical group 71%; p = 0.19) our data do not prove that intervention is better than medical treatment, largely because the decision on intervention was not randomised. A prospective trial would be required to answer this important question.

Adult↗
PubMed1989

Human lymphokine-activated killer cells develop syngeneic killing ability.

Lymphokine-activated killer (LAK)-cell therapy has emerged as a new strategy in designing protocols for the treatment of cancer. However, in its present clinical form, it has not fulfilled the early promise shown in murine models of human metastatic disease. In an attempt to gain understanding as to why this might be the case, we measured the ability of human LAK cells, generated in vitro for 4 days, to kill LAK cells from the same donor that had been exposed to IL-2 in vitro for 8 days, and vice versa. In eight separate experiments using different donors, 4-day ('early') LAK cells were able to kill syngeneic 8-day ('late') LAK cells, while late LAK cells were also able to kill early LAK cells. Strong killing was observed in both directions, which was almost total in one instance. In order to assess the development of this phenomenon, early LAK cells were tested for their ability to kill syngeneic LAK cells that were 1, 2, 3 or 4 days 'older' and the reciprocal experiment conducted using late LAK cells as effectors. The results illustrate a strong capacity for the development of syngeneic killing by human LAK cells. The possible implications of this phenomenon for the clinical administration of LAK cell/IL-2 therapy are discussed.

Cells, Cultured↗
PubMed1988

Caesarean section: a national study.

Although the use of caesarean section (CS) continues to be debated, the demographic characteristics of the affected population have received little attention. This paper shows that in New Zealand during 1983-84, a CS was performed on 9.6% of delivered women between the ages of 15-44. The rate increased with maternal age (p less than 0.01), and was highest for 'single' women (11.3/100) and Pacific Island women aged 35-44 (21/100). There was a significantly (p less than 0.05) high rate in the Auckland and South Otago hospital board districts, but a low rate (p less than 0.05) in the Ashburton, Nelson, Canterbury, Southland, Taumaranui, Waiapu, Wairarapa, Wanganui, and Wellington board districts. The rate was also high (p less than 0.01) in the principal teaching hospitals. Long labour (15.2%), malposition and malpresentation of the fetus (14.7%) were the leading reasons for performing a CS. The paucity of national data on a number of other highly relevant birth and maternal factors hinders the further definition of the epidemiological patterns of CS in New Zealand.

Adolescent↗
PubMed1988

A new epitope on human myelin basic protein arising from cleavage by a metalloendoprotease associated with brain myelin membranes.

Human brain myelin membranes were incubated to allow activity of an associated metalloendoprotease which cleaves myelin basic protein (MBP). A 10.3 kDa C-terminal fragment of MBP, peptide C, isolated from the incubation medium had a blocked N-terminal. After treatment with pyroglutamyl aminopeptidase, N-terminal sequencing indicated that Gln74 of MBP formed the N-terminal residue of peptide C. A rabbit antiserum was raised to a synthetic peptide containing the sequence Pyroglu-Lys-Ser-His-Gly-Arg, corresponding to the first six residues of peptide C. By immunoblotting this serum reacted with peptide C but not with intact MBP. The data indicate that cleavage of MBP by a myelin-associated protease engenders a new epitope.

Amino Acid Sequence↗
PubMed1987

Using a national register for the epidemiological study of congenital heart defects.

Data validity is a fundamental problem in epidemiology. An objective of birth defect registers is the collection of high quality data, often from a number of sources, for use in epidemiological research. This paper examines the use of data from a national register in New Zealand in the study of congenital heart defects. The prevalence rates of congenital heart defects are shown to depend on the definition of the terms employed, the methods and completeness of the case ascertainment, the correctness of the diagnoses, the nature and size of the population under study, and the duration of followup. Recommendations are made for increasing the utility of this register in the study of this major group of malformations.

Autopsy↗
PubMed1986

Sports injuries in New Zealand.

A study of 5108 patients admitted to public hospitals with sports injuries was undertaken for the years 1981-82. Winter sports caused 80% of the injuries, with 58.1% of the cases having been involved in either rugby union or league. Almost 40% of all the injuries were to the head, and fractures were the most common type of injury. Sports-specific injury patterns were found.

Adolescent↗