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Biomedical subjects

I Gray

Publications and source records attributed to I Gray.

At least 19 recordsLinked to original sources
PubMed2004

Haemophilus influenzae as a possible cause of Guillain-Barré syndrome.

Recent reports have contained conflicting results on the relationship between antecedent Haemophilus influenzae infection and Guillain-Barré syndrome (GBS). To investigate the prevalence of H. influenzae infection in GBS patients in a British population, we carried out a retrospective study with 62 consecutive GBS patients and 63 normal controls of similar age and sex. Whole bacteria of both encapsulated and nonencapsulated strains of H. influenzae were employed as antigens in an enzyme-linked immunosorbent assay (ELISA) for anti-H. influenzae IgG, IgM and IgA antibodies. Elevated antibodies of two or three classes were found in one GBS patient and none in the normal controls. Six GBS patients had IgG antibodies against nonencapsulated H. influenzae compared with only one in the normal control group (p=0.06). Western blot for IgG antibody showed that all the sera with IgG antibodies recognized the lipopolysaccharide (LPS) of both strains of H. influenzae. Antiganglioside GM1 antibody was not associated with anti-H. influenzae antibody in our study. Absorption with encapsulated or nonencapsulated H. influenzae, Campylobacter jejuni and Escherichia coli before testing on Western blot showed that only nonencapsulated H. influenzae absorbed the anti-LPS antibodies. In conclusion, there is a possible but rare association of GBS with nonencapsulated H. influenzae in the UK.

Adolescent↗
PubMed2003

A variant of multifocal motor neuropathy with acute, generalised presentation and persistent conduction blocks.

OBJECTIVE: Multifocal motor neuropathy with persistent conduction blocks is classically described as a chronic neuropathy with progressive onset, and acute forms have not previously been characterised. We report four cases of severe motor impairment with acute and generalised onset and with persistent motor conduction blocks. PATIENTS AND RESULTS: An acute tetraparesis with diffuse areflexia but little or no sensory disturbance was the clinical picture. Serial electrophysiological tests showed persistent multifocal motor conduction blocks with absent F waves in most tested motor nerves. No or minor abnormalities of the sensory nerve action potentials were observed. Cerebrospinal fluid contained normal or mildly increased protein levels (<1 g/l) without cells. Campylobacter jejuni serology was negative in three patients and consistent with past infection in one patient. Anti-ganglioside antibodies were positive in three patients. A five day course of intravenous immunoglobulins produced nearly complete symptom resolution in three patients and was ineffective in one patient. CONCLUSION: Because of the persistence of multifocal motor conduction blocks for several weeks or months as the isolated electrophysiological feature, these cases could not be consistent with Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. They suggest an original variant of multifocal motor neuropathy with an acute and generalised initial presentation and persistent motor conduction blocks affecting all four limbs.

Acute Disease↗
PubMed2000

Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource.

Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol-SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations-with consequent benefits for the analysis of gene function and the identification of novel pathways.

Animals↗
PubMed2000

Cyclooxygenase active bioflavonoids from Balaton tart cherry and their structure activity relationships.

Several flavonoids and isoflavonoids isolated from Balaton tart cherry were assayed for prostaglandin H endoperoxide synthase (PGHS-1) enzyme or cyclooxygenase isoform-1 (COX-1) activity. Genistein showed the highest COX-1 inhibitory activity among the isoflavonoids studied, with an IC50 value of 80 microM. Kaempferol gave the highest COX-1 inhibitory activity among the flavonoids tested, with an IC50 value of 180 microM. The structure-activity relationships of flavonoids and isoflavonoids revealed that hydroxyl groups at C4', C5 and C7 in isoflavonoids were essential for appreciable COX-1 inhibitory activity. Also, the C2-C3 double bond in flavonoids is important for COX-1 inhibitory activity. However, a hydroxyl group at the position decreased COX-1 inhibitory activity by flavonoids.

Cyclooxygenase 1↗
PubMed2000

Visually guided collision avoidance and collision achievement.

To survive on today's highways, a driver must have highly developed skills in visually guided collision avoidance. To play such games as cricket, tennis or baseball demands accurate, precise and reliable collision achievement. This review discusses evidence that some of these tasks are performed by predicting where an object will be at some sharply defined instant, several hundred milliseconds in the future, while other tasks are performed by utilizing the fact that some of our motor actions change what we see in ways that obey lawful relationships, and can therefore be learned. Several monocular and binocular visual correlates of the direction of an object's motion relative to the observer's head have been derived theoretically, along with visual correlates of the time to collision with an approaching object. Although laboratory psychophysics can identify putative neural mechanisms by showing which of the known correlates are processed by the human visual system independently of other visual information, it is only field research on, for example, driving, aviation and sport that can show which visual cues are actually used in these activities. This article reviews this research and describes a general psychophysically based rational approach to the design of such field studies.

Journal Article↗
PubMed2000

Gender and drought: experiences of Australian women in the drought of the 1990s.

A unique collaborative, sociological study undertaken during 1995-7, explored the social construction of drought as a disaster, looking at farm families in two Australian states: Queensland (beef producers) and New South Wales (sheep/wheat producers). A decision was made to interview the women and men separately to test our hypothesis that there would be gender issues in any analysis of a disaster, but particularly one which has had so much long-term impact on individuals, families and communities, such as drought. Interviews were conducted with over 100 individuals male and female. We conclude that drought as a disaster is a gendered experience. The paper draws on the narratives of some women involved in the study to identify 'themes of difference' which confirm the necessity to maintain gender as a variable in all studies of the social impacts of disaster.

Adaptation, Psychological↗
PubMed1999

Antiganglioside antibodies in Guillain-Barré syndrome after a recent cytomegalovirus infection.

OBJECTIVE: To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection. METHODS: Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. RESULTS: IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. CONCLUSION: Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.

Adolescent↗
PubMed1994

Phase I study of interleukin-2 combined with interferon-alpha and 5-fluorouracil in patients with metastatic renal cell cancer.

Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) each has produced a 15%-20% response in metastatic renal cell cancer. Combining IFN-alpha with either IL-2 or 5-fluorouracil (5-FU) enhanced IFN-alpha activity. We have therefore conducted a Phase I Study combining IL-2, IFN-alpha, and 5-FU. The patients were continuously infused with IL-2 (1-3 x 10(6) u/m2) and 5-FU (600-750 mg/m2) for a 5-day period every 28 days, and IFN-alpha (4-5 x 10(6) u/m2) was injected subcutaneously daily. Lymphokine-activated killer (LAK) and natural killer (NK) cell activity was measured on days 0 and 8. Twenty-one patients received 76 courses. All primary tumors were controlled by surgery (81%) or angioinfarction. Hematologic toxicity was mild; median nadir of platelets was 117 K/microL and of granulocytes was 1.2 K/microL. Dose-limiting toxicity included mucositis, liver damage, and hypotension. No treatment-related death occurred, and only one patient required intensive-care-unit support. Two patients had an objective response, one of which was a complete response. Increased LAK cell and NK cell activity occurred at all IL-2 dose levels. Simultaneous delivery of IL-2, IFN-alpha, and 5-FU is safe and shows antitumor and biologic activity. 5-FU did not appear to suppress IL-2-induced LAK and NK cell activation. Maximum tolerated dose of the three-drug combination is IL-2, 2 x 10(6) u/m2, 5-FU 600 mg/m2, and IFN-alpha, 4 x 10(6) u/m2.

Adult↗
PubMed1989

Uptake and subcellular distribution of cadmium in resting and mitogen-activated lymphocytes and its relationship to a metallothionein-like protein.

The effects of cadmium on the immune system have been extensively studied, although relatively little is known about the nature of the interaction between cadmium and lymphocytes. We describe studies that examine the uptake and subcellular distribution of cadmium in resting and mitogen-activated mouse splenic lymphocytes exposed to cadmium in vitro. Mitogen activation was associated with an increased uptake and altered subcellular distribution of cadmium, compared to resting (nonmitogen-activated) lymphocytes. In both resting and mitogen-activated lymphocytes the total uptake of cadmium was concentration-dependent. However, compared to resting lymphocytes, in mitogen-activated lymphocytes, cadmium tended to distribute out of the nuclear and into the cytoplasmic fraction. The Sephadex G-75 exclusion chromatography profile revealed the presence of a cadmium-binding protein eluting identically to metallothionein in mitogen-activated, but not in resting, lymphocytes. The presence of this protein in mitogen-activated lymphocytes is consistent with the differences in subcellular distribution of cadmium reported. Further, the difference between resting and mitogen-activated lymphocytes in the production of this protein, and the known genetic differences in the metallothionein inducibility, may explain some of the reported variability in the effects of cadmium on the immune system.

Animals↗
PubMed1985

Inhibition by cadmium of thymidine metabolism in concanavalin A-activated murine splenocytes.

Cadmium has been shown to cause significant inhibition of lymphocyte metabolism, including DNA synthesis, in both in vitro and in vivo studies. In order to understand more clearly the modification of DNA synthesis, this study has examined the metabolism of radiolabelled thymidine in splenocytes exposed to cadmium in vitro. T-lymphocyte-enriched splenocytes were incubated for 48 h with or without Conconavalin A. Cadmium (10 microM) was present during the full period of culture or added at various times after the initiation of the culture. Thymidine metabolism was assessed by examining intracellular metabolite pools, incorporation into DNA, thymidine kinase activity and thymidine membrane transport. Cadmium had little effect on any of these parameters in non-mitogen-stimulated cells. However, in concanavalin A-stimulated cells exposed to cadmium for the full period of culture, the changes in thymidine metabolism normally associated with mitogen activation including increased thymidine incorporation into DNA, expansion of the thymidine di- and triphosphate pools and increased thymidine kinase activity did not occur. Some membrane transport of thymidine did occur but it was less than that of non-cadmium-exposed concanavalin A-stimulated cells. Approximately 90% inhibition of thymidine incorporation into DNA occurs when cadmium is added any time during the first 26 h of culture. When cadmium is present only during the final 6 h of culture, the incorporation is inhibited by approximately 60%. Furthermore, the presence of cadmium during only the last 2 h of culture was shown to inhibit the membrane transport of thymidine, but had no effect on thymidine kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of anaesthetic technique on deep vein thrombosis. A comparison of subarachnoid and general anaesthesia.

Forty patients with fractured neck of femur were allocated randomly to undergo surgery under general anaesthesia (GA) or subarachnoid anaesthesia (SAB). After operation, the incidence of deep vein thrombosis (DVT), assessed by venography, was found to be 40% in the SAB group, which was significantly lower than the incidence (76.2%) in the GA group. These observations may account for the previously reported effect of SAB, in comparison with GA, in reducing early postoperative mortality in this category of patient.

Adult↗
PubMed1984

Glycogen regulation in LPS-stimulated murine splenocytes.

Enzymatic glycogen regulation in mouse splenocytes cultured in vitro with and without LPS, was studied from 0-72 h. Increased [3H]glucose uptake and hexokinase activity demonstrated the activation of cells treated with LPS. There was a greater time-dependent increase of cellular glycogen content in LPS-stimulated cells as compared to control. Glycogen synthetase I in LPS-stimulated cells increased about 200% above control cells to a plateau at 48 h, while in unstimulated cells there was little increase throughout. Glycogen synthetase D increased continually to 72 h in both groups. In the stimulated cells, phosphorylase increased only 90% above control cells up to 48 h. It was concluded that the increased glycogen content of LPS-stimulated cells seen at 48 h may result from an increase in both glycogen synthetase I and D activity compared to lesser increase in hydrolysis. However, between 48 and 72 h, the period of RNA and DNA increased synthesis, the glycogen content of stimulated cells did not increase further, consistent with the observation that synthetase I activity remained constant and synthetase D decreased. Thus, following mitogenic stimulation, the net effect of the enzymatic regulation is to increase cellular glycogen, as an energy source for subsequent events.

Animals↗
PubMed1984

Modification of glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12, isolated from rainbow trout during acclimation at 5 or 15 degrees C--I. Changes in the activity of individual muscle isolates as evidence for variable adaptive responses.

The mean Km and Vmax values for G3PDH isolated from the lateral muscle of cold-adapted (5 degrees C) rainbow trout, Salmo gairdneri, were twice those of enzyme from warm-adapted (15 degrees C) trout when assayed at 7 degrees C but not at any other temperature. The entropy of activation of warm enzyme was about 3 times that of cold enzyme. However, enthalpy or free energy of activation among acclimation groups differed less or not at all. Individual G3PDH isolates within either adaptation group differed in kinetic characteristics.

Acclimatization↗
PubMed1984

Modification of glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12, isolated from rainbow trout during acclimation at 5 or 15 degrees C--II. Biochemical characterization of G3PDH muscle isolates.

G3PDH was isolated from the lateral muscle of rainbow trout (Salmo gairdneri) acclimated at 5 degrees C (cold) and 15 degrees C (warm). No differences were found in muscle concentration, molecular weights, isoelectric focusing patterns, amino acid compositions or peptide maps between cold and warm isolates. Cold and warm G3PDH contained mannose in variable concentration but no other prosthetic groups.

Acclimatization↗
PubMed1982

Strain variations in cadmium-induced suppression of lymphocyte transformation in mice.

Cadmium is an environmental pollutant which has been shown in numerous studies to significantly affect immune responses. However, a review of the literature reveals many inconsistencies, both qualitative and quantitative, in the effects of cadmium on the immune system. In the present study, we examine the influence of genetic background on the effects of cadmium using lymphocyte transformation as an index of immunocompetence. Cadmium was added in vitro to mitogen and non-mitogen stimulated splenocyte cultures obtained from Balb/c, C57BL and C3HeB mice. Cadmium, 1-30 microM, was associated with a dose-dependent, linear inhibition of lymphocyte transformation in all strains. In unstimulated and Con A-stimulated cultures, the cadmium-inhibition plots were parallel but non-coincident in the three strains of mice with C57 being the most susceptible and C3H the most resistant to the inhibitory effects of cadmium. For LPS-stimulated lymphocyte transformation, the cadmium inhibition plots had different slopes in the three strains of mice suggesting a possible difference in the mechanism of action of cadmium. The relationship between these findings and cadmium-induced cytotoxicity as well as metallothionein synthesis are discussed.

Animals↗
PubMed1982

Modification of skin-graft rejection and acceptance by low concentrations of cadmium in drinking water of mice.

Skin allograft rejection and isograft acceptance was studied in Balb/c mice exposed to 0, 0.01, 0.1, 1.0, or 10.0 ppm cadmium in drinking water beginning 4 wk prior to grafting. Cadmium exposure was associated with a dose-dependent acceleration of the rejection of allografts prepared from the tail skin of C57/BL mice. The mean time to allograft rejection decreased from 10.4 d in non-metal-exposed recipients to 7.4 d in mice exposed to 10 ppm cadmium. Cadmium exposure was also associated with a dose-dependent increase in the time to isograft acceptance (8.6 d in control mice compared to 11.0 d in mice exposed to 10 ppm cadmium). In addition, some isografts were rejected by animals exposed to 1 or 10 ppm cadmium. It is suggested that a cadmium-induced modification of the wound-healing process could explain both the allograft and isograft response, although an effect of cadmium on the immune response to histoincompatible tissue may also play a role in the accelerated allograft rejection.

Animals↗