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Biomedical subjects

I D Gardner

Publications and source records attributed to I D Gardner.

At least 19 recordsLinked to original sources

Hepatitis B virus markers in children and staff in Northern Territory schools.

OBJECTIVE: To measure the prevalence of hepatitis B virus (HBV) infection in children and staff at Northern Territory schools. DESIGN: Children in Years 5-7 in 24 selected primary schools were invited, with parental consent, to provide demographic and ethnic details, and a capillary blood sample for tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). School staff participated on a similar basis. PARTICIPANTS: 1104 children, comprising 556 from ethnic groups (originating from the United Kingdom, Ireland and northern Europe) previously reported as "low HBV prevalence", 439 Aboriginal Australians, and 109 from "other" ethnic groups (originating from Asia, the Pacific, the Middle East and southern Europe); and 209 school staff, comprising 180 from "low HBV prevalence" ethnic groups, and 29 from Aboriginal and other ethnic groups. RESULTS: Prior HBV infection (i.e. serum positive for HBsAg or anti-HBs) was detected in 28.7% of children (46.9% of 439 Aborigines; 13.7% of the 556 children from the "low prevalence" groups and 32.1% of the 109 from the "other" groups). HBsAg was detected in 8.2% of Aboriginal children, in 0.36% of those from "low prevalence" groups, and in 1.8% of those from the "other" groups. Aboriginal children in rural schools had the highest prevalence of HBV: 5.4% were positive for both HBsAg and anti-HBs, and an additional 9.8% were positive for HBsAg alone. In urban schools, the prevalence was highest in the "other" ethnic groups. For school staff, the prevalence of HBV infection was 12.8% for those from "low prevalence" ethnic groups, and 37.9% for those from all remaining groups (including Aborigines). CONCLUSION: In the Northern Territory the prevalence of past HBV infection is high in children and school staff from ethnic groups previously known to be at higher risk of HBV infection. For students and staff from ethnic backgrounds expected to be at low risk, HBV prevalence is greater than in individuals from similar backgrounds in other parts of Australia. HBV vaccination is now offered to all infants in the Northern Territory. These results also provide a rationale for the more widespread use of HBV vaccine in other situations where significant HBV transmission might occur.

Child

Primary or secondary anterior chamber lens implantation after extracapsular cataract surgery and vitreous loss.

Whilst an anterior chamber lens implant (AC IOL) can be implanted during extracapsular cataract extraction with vitreous loss managed by anterior vitrectomy, lens implantation as a secondary procedure may avoid complications. We reviewed 47 consecutive cases of vitreous loss, 37 managed with primary and 10 with secondary AC IOLs. There was no significant difference in the level of final visual acuity but, as expected, it was reached earlier in the primary group (p less than 0.001). In the secondary group post-operative astigmatism was less marked (p less than 0.05) and the AC IOL haptic feet were correctly sited in the angle more frequently (p less than 0.05). Primary implant patients experienced more recurrent attacks of anterior uveitis (p less than 0.01) although the incidence of cystoid macular oedema and retinal detachment did not differ significantly. The results suggest that correct AC IOL positioning is more likely with a secondary procedure and that post-operative complications are fewer.

Cataract Extraction

Preferential binding of Chlamydia trachomatis to subsets of human lymphocytes and induction of interleukin-6 and interferon-gamma.

The interactions between Chlamydia trachomatis and human blood mononuclear leukocytes were studied using flow cytometry, immunofluorescence, electron microscopy and cytokine assays. Under serum-free conditions, elementary bodies (EB) of C. trachomatis were found to bind to human T lymphocytes as well as to B cells and monocytes/macrophages (M phi). For all cell types the binding was saturable, rapid, temperature-independent and independent of the chlamydia-specific serological status of the donor. Similar proportions of T and B cells bound EB at similar levels. In the T cell population, proportionally less CD8+ cells bound EB. Whereas M phi phagocytosed and destroyed the bound micro-organisms for lymphocytes, the Chlamydia remained at the surface, adherent to morphologically featureless membrane areas and showed no evidence of uptake even after long periods at 37 degrees C. Host molecules modulated these basic binding patterns: a heat-stable serum factor inhibited EB binding to T cells and a heat-labile serum factor enhanced binding to B cells. Stimulation with C. trachomatis EB rapidly elicited cytokine production by lymphocytes including interleukin-6 from B cells and interferon-gamma (IFN-gamma) from T and/or nonT/nonB cells. The responses were irrespective of the serological status of the donor. The findings suggest that C. trachomatis-leucocyte interactions may differ from the interactions of other bacteria and human leucocytes. The possible relationship between leucocyte-binding, cytokine induction, and the pathognomonic development of lymphoid follicles during mucosal C. trachomatis infections is discussed.

Bacterial Adhesion

Optic nerve avulsion due to forced rotation of the globe by a snooker cue.

We report a case of partial avulsion of the optic nerve caused by sudden rotation of the globe due to a snooker cue injury. Minimal direct ocular trauma occurred. This case supports the belief that sudden rotation of the globe is the major mechanism of optic nerve avulsion. We include the first results of ultrasound examination that demonstrate optic nerve injury in such a case and believe that, in conjunction with fluorescein angiography and computerised tomography, it is important in the full evaluation of such cases.

Adult

Maternal T cells and human pregnancy outcome.

Mothers who had just delivered babies of normal birthweight showed significant reductions in the numbers of circulating T and B lymphocytes and of the CD4 T lymphocyte subset. This is consistent with the immunosuppression that occurs in a normal pregnancy. In contrast, the mothers of low birthweight infants did not show these reductions and had circulating lymphocyte numbers not significantly different from normal controls. This suggests that a component of intra-uterine growth retardation may be immunopathological, owing to a failure of the immunosuppressive mechanisms of pregnancy that might normally prevent the fetus from immunological attack.

Adult

Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal community.

Health status was assessed in 39 kava users and 34 non-users in a coastal Aboriginal community in Arnhem Land. Twenty (27%) respondents were very heavy (mean consumption, 440 g/week) users of kava; 15 (21%) respondents were heavy (310 g/week) users of kava and four (5%) respondents were occasional (100 g/week) users of kava. Kava users were more likely to complain of poor health and a "puffy" face, and were more likely to have a typical scaly rash, and slightly-increased patellar reflexes. Very heavy users of kava were 20% underweight and their levels of gamma-glutamyl transferase were increased greatly. Albumin, plasma protein, urea and bilirubin levels were decreased in kava users, and high-density lipoprotein cholesterol levels were increased. Kava users were more likely to show haematuria, and to have urine which was poorly acidified and of low specific gravity. The use of kava was also associated with an increased red-cell volume, with a decreased platelet volume and with a decreased lymphocyte count. Shortness of breath in kava users was associated with tall P waves on a resting electrocardiogram, which provided suggestive evidence of pulmonary hypertension. In common with other Aboriginal communities, there was evidence of decreased lung volumes, a high carriage rate of hepatitis B surface antigen, and of other morbidity that was unrelated to the use of kava. On the basis of these findings, there is a strong rationale for urgent social action to improve health in Aboriginal communities and, in particular, to reduce the consumption of kava and to improve the nutritional status of kava users.

Adolescent

Evaluation of phagocytic function in Mycobacterium lepraemurium infection.

Infection of mice with Mycobacterium lepraemurium caused significant functional alterations of the mononuclear phagocyte system. Accelerated clearance of sheep red blood cells was consistently demonstrated throughout the infection and the infected mice showed progressive anaemia. Infected mice showed an enhanced ability to limit growth of phagocytosed Listeria monocytogenes in spleens during the early stages of infection, whereas moribund leprous mice lost this ability. Autoradiography showed that uninfected Kupffer cells and splenic macrophages of moribund mice could still phagocytose Listeria, suggesting that MLM infection did not affect the capacity of Listeria to localize to macrophages but interfered in some way with subsequent killing of such bacteria. The possible mechanisms underlying these observations are discussed.

Anemia

The effect of in vivo modulation of macrophage activities on Mycobacterium lepraemurium infection.

During the early stage of Mycobacterium lepraemurium (MLM) infection in mice, the mononuclear phagocyte system (MPS) was activated non-specifically as demonstrated by enhanced listericidal activity. Such listericidal activity could be further increased by Corynebacterium parvum treatment, indicating that MLM was not a good MPS stimulant. Corynebacterium parvum treatment conferred only marginal protection upon mice during MLM infection, as shown by the slight but significant prolongation of survival time and decreased bacillary load. In contrast, mice could not control splenic Listeria growth in the later stage of infection regardless of C. parvum treatment. Adoptive transfer of Listeria-immune spleen lymphocytes, however, did significantly suppress splenic Listeria growth. The significance of these findings is discussed.

Animals

Lectin binding patterns and monoclonal antibodies to epidermal antigens in tumours of the skin.

Monoclonal antibodies to epidermal antigens and cell surface carbohydrate markers, as defined by lectin binding, were used to analyze the cells in squamous and basal cell carcinomas of the skin (SCC and BCC). The cells in BCC failed to stain with the lectin peanut agglutinin (PNA), which stains surface carbohydrates of cells in the stratum spinosum and stratum granulosum layers of normal epidermis, confirming histological observations that the cells in BCC are incapable of differentiation beyond the basal cell stage. Conversely, the central cells in SCC did react with PNA, suggesting that they can differentiate to a stage equivalent to the stratum spinosum of epidermis. The zone immediately surrounding BCC differed from that around SCC in lectin binding and staining with antisera to laminin and fibronectin, an observation which could be connected with the failure to metastasize. It was of interest that histologically normal skin immediately adjacent to and overlying these tumours showed marked changes in reaction with markers of normal epidermis. The outer layers of this epidermis showed aberrant retention of the lower molecular weight cytokeratins marked by the monoclonal antibodies LMM2 and LMM3, and occasional strong staining of individual cells by the stratum granulosum-reactive LMM1. These changes appear to be indicative of a 'premalignant' state in these cells and the monoclonal antibodies are thus potentially useful reagents for early detection of skin malignancies.

Antibodies, Monoclonal

Production and characterization of monoclonal antibodies reactive with subsets of epidermal cells.

Monoclonal antibodies were raised against an extract of human callus to provide markers of cell differentiation. Three antibodies, LMM1, LMM2 and LMM3, have been isolated and react with different histological structures in skin. LMM1 reacts with two distinct proteins of 62-65 kD molecular weight and stains cells in the stratum spinosum and stratum granulosum of normal epidermis. This antibody stains a high proportion of cultured epidermal cells showing a diffuse cytoplasmic reactivity with nucleolar staining also being present in some cells. LMM2 reacts with several lower molecular weight proteins, the two major bands being 38 kD and 44 kD. It stains basal epidermal cells strongly and stratum spinosum cells less strongly. A population of cultured keratinocytes reacts with an intense fibre stain suggesting that this antibody is directed against an intermediate filament or intermediate filament-associated protein. LMM3 reacts with a 48 kD protein. Although it does not stain cells in normal epidermis its staining of a subpopulation of hair follicle cells is consistent with this protein being a cytokeratin. It also stains a population of cultured keratinocytes, the main reactivity being against mitotic cells. The anti-cytokeratin or anti-cytokeratin-associated reactivity of these three antibodies is supported by their altered reactivities against psoriasis epidermis, where modifications of cytokeratin biosynthesis are known to occur.

Animals

An enzyme immunoassay for rapid isotyping of monoclonal antibodies.

An enzyme-immunoassay has been developed for rapid isotyping of murine monoclonal antibodies. This assay has several advantages over the commonly used typing methods. It does not require the presence of specific antigen. Typing plates can be prepared in advance and stored frozen. Unequivocal results can be obtained in 2 h, and the urease indicator system produces a vivid colour change that can be read visually.

Animals

Experimental murine leprosy: a biochemical study emphasizing lysosomal enzyme changes in vivo and enzyme secretion by macrophages in vitro.

This study was undertaken to identify biochemical alterations in serum, lymphoid organs, and peritoneal macrophages (PM) which reflect the histopathology of experimental Mycobacterium lepraemurium (MLM) infection in mice. A significant increase of acid phosphatase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, and lysozyme was found in serum, spleen, and liver homogenates of mice infected intraperitoneally (ip) with MLM. PM from infected mice showed a substantially greater rate of secretion of beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, and acid phosphatase than PM from normal mice. There was, however, no significant difference in the ability of PM from BALB/c and C57BL/6 mice to secrete such enzymes in vitro. There was also a significant increase in all these enzymes in PM in the early stage of infection but they dropped to values lower than normal in the advanced stage of infection despite the fact that such cells increased in size and protein content as the infection progressed. Infected mice were also found to have progressively elevated levels of serum lactic dehydrogenase, glutamic oxaloacetic, and glutamic pyruvic transaminases which indicated damages of hepatocytes and other tissues. Values of other blood components were also reported. Both BALB/c and C57BL/6 strain of mice, which are susceptible to the ip route of MLM infection, showed an indistinguishable pattern of biochemical alterations as reflected by their similar histopathological changes in various organs. BALB/c mice, which are still susceptible to subcutaneous (sc) route of infection showed similar characteristic changes in various serum components as before. In contrast, C57BL/6 mice, which are resistant to MLM infection sc, showed insignificant alterations in most of these biochemical parameters.

Animals

Immunosuppressive activities of peritoneal and splenic macrophages in murine leprosy: effect on lymphocyte transformation and tumor growth.

The ability of peritoneal macrophages (PM) and splenic macrophages (SM) to suppress tumor growth and lymphocyte transformation in vitro was studied in infected mice with Mycobacterium lepraemurium (MLM). Both PM and SM of leprous mice showed cytostatic activity against tumor cells in vitro. However, such cells showed significantly less cytostatic activity on a per cell basis than highly activated macrophages obtained from Corynebacterium parvum-immunized mice. Furthermore, this cytostatic activity declined as the infection progressed. Mitogen-induced transformation of splenic lymphocytes was also suppressed in the presence of adherent PM and SM from leprous mice. PM from leprous mice showed significantly less activity than PM from C. parvum-immunized mice in terms of suppression of lymphocyte transformation. Moreover, PM from leprous mice treated with C. parvum or sodium thioglycollate broth demonstrated significantly less ability to suppress lymphocyte transformation than did PM from similarly treated normal mice or untreated leprous mice. These findings demonstrated that MLM infection stimulates the mononuclear phagocyte system but does not activated it to the extent that it confers enhanced resistance to MLM on the host.

Animals

Characterization of macrophage function in Mycobacterium lepraemurium-infected mice: sensitivity of mice to endotoxin and release of mediators and lysosomal enzymes after endotoxin treatment.

Mycobacterium lepraemurium (MLM) infection increases the sensitivity of mice to lipopolysaccharide (LPS) as do infections with other intracellular parasites. Tumour necrosis factor (TNF), lymphocyte activating factor (LAF) and increased levels of various lysosomal and cytoplasmic enzymes were found in serum samples taken 2 h after intravenous injection of a small dose of LPS suggesting that damage to a variety of cell types, including macrophages, had occurred. Sera from moribund MLM-infected mice not injected with LPS also demonstrated significant levels of TNF compared with controls. Intravenous injections of silica into leprous mice also led to increased levels of serum lysosomal and cytoplasmic enzymes but did not give rise to a significant amount of TNF or LAF. Moreover, in contrast to LPS treatment, the injection of silica did not lead to the death of leprous mice. These findings suggest that the phagocytic cells of the infected animals did not contribute to the production of these mediators after LPS challenge. Rather, the non-phagocytic granuloma macrophages or other unidentified cell types seemed to provide the main source of the monokines TNF and LAF in vivo in the present model. These mediators may have important implications for the immunopathology of MLM infection.

Animals

Macrophage function in Mycobacterium lepraemurium infection: morphological and functional changes of peritoneal and splenic macrophages in vitro.

Morphological and functional changes in peritoneal macrophages (PM) and splenic macrophages (SM) from mice infected with Mycobacterium lepraemurium were investigated. A decrease in the number but an increase in the size of PM were observed during the infection. PM were vacuolated, and a small proportion of them were observed in cell division. They demonstrated greater ability to adhere and spread in vitro, enhanced phagocytosis of immunoglobulin G (IgG) and IgM erythrocytes, and greater phagocytosis and killing of Candida sp., when compared with normal resident PM. In contrast, parasitized SM demonstrated significantly reduced phagocytic ability, whereas heavily parasitized SM neither spread nor phagocytosed Candida sp. The random migration and chemotactic responsiveness of PM from infected animals were also enhanced. These results indicated the persistent activation of PM but the suppression of some activities of SM during M. lepraemurium infection.

Animals

Simultaneous bilateral intraocular surgery.

During the past ten years, the frequency of bilateral simultaneous intraocular surgery has increased and the majority have been cataract extractions. Two hundred and fifty-one patients have had this operation. The pre- and postoperative acuities and the complications have been tabled and the assessment indicates that this is a safe and successful approach considering the age of the patients and the associated pathology. There was no bilateral operative disaster. Of 232 patients whose post-operative acuities were recorded and are known, no patient had worse binocular acuity following bilateral simultaneous cataract extraction. Hospital time in the clinics, the ward and the operating theatre has been saved and the patients are more quickly returned to balanced binocular vision.

Aged

Depressed human monocyte function after influenza infection in vitro.

Human monocytes were separated from peripheral blood of 22 normal healthy adults and incubated with Hsw1N1 influenza virus or diluted allantoic fluid. The treated monocyte populations were tested for five parameters of monocyte function. Influenza infection markedly inhibited the monocyte chemotactic response and the killing of Candida albicans; infection also depressed phagocytosis, slightly reduced spreading, but did not affect adhesion to glass. These results suggest that influenza virus may also have an inhibitory effect on monocyte function in vivo and help to explain the increased susceptibility to secondary bacterial infection and the general immunosuppression seen in influenza infection.

Adult

Monocyte function in ageing humans.

Peripheral blood monocytes from hospitalised patients greater than 60 years of age and less than 35 years, and those from healthy normal controls less than 35 years, were tested for a range of functional and physiological properties, comprising chemotaxis under agarose, the ability to phagocytose and kill Candida albicans, adhesion to glass and spreading on glass. No significant difference was found between young and old groups, nor between hospitalized and non-hospitalized groups in respect of any parameter. There was some decline in phagocytosis and in spreading in a very old subgroup (greater than 75 years), but this was not statistically significant. This study showed that phagocytic cell function in the elderly does not decline at the same rate as the specific immune response and thus cannot directly account for the increased incidence of infection in the aged.

Adhesiveness