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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 145 records · Page 8Linked to original sources

Multifactorial immunologic lung disease: a case report.

BACKGROUND: Allergic asthma, allergic bronchopulmonary aspergillosis, and hypersensitivity pneumonitis are all forms of immunologically mediated lung disease. Recognition that more than one of these diseases may co-exist is necessary for proper patient management. OBJECTIVE: To report a case of extrinsic (cat) asthma, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and potentially fatal asthma. Immunologic mechanisms and treatment of these diseases are discussed. METHODS: The study is a case report from a university hospital setting. Serum precipitating antibodies against avian antigens were measured using gel-diffusion technique. Serum IgE levels were measured and skin testing was performed to selected antigens. RESULTS: The patient had positive cutaneous reactivity to cat antigen and Aspergillus. Serology for allergic bronchopulmonary aspergillosis and serum precipitating antibodies to finch extract were positive. Symptoms improved and prednisone requirements decreased after removal of finches. CONCLUSION: A case of cat asthma, potentially fatal asthma, allergic bronchopulmonary aspergillosis, and hypersensitivity pneumonitis is presented. Early recognition and treatment of multifactorial immunologic lung disease with avoidance measures and use of corticosteroids can prevent progressive respiratory damage.

Adult↗

Allergic bronchopulmonary aspergillosis presenting with cough variant asthma and identifiable source of Aspergillus fumigatus.

BACKGROUND: A 76-year-old man developed allergic bronchopulmonary aspergillosis initially presenting with cough variant asthma. Symptoms worsened after exposure to ground mulch which was an identifiable source of Aspergillus fumigatus. Symptoms improved after corticosteroids and avoidance measures were instituted. OBJECTIVE: To report a case of allergic bronchopulmonary aspergillosis presenting as cough variant asthma with identifiable source of Aspergillus fumigatus. METHODS: Single case report. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion techniques. Total IgE, specific IgE, and IgG indices were measured by ELISA. Cutaneous reactivity to Aspergillus fumigatus was also tested. RESULTS: Skin test and serum precipitating antibodies to Aspergillus fumigatus were positive. Precipitins were also detected between Aspergillus fumigatus and the mulch. Total serum IgE was 538 IU/mL (1290 ng/mL) which declined to 228 IU/mL (544 ng/mL) after corticosteroid therapy. IgE index = 1.10 and IgG index = 2.86. CONCLUSION: Allergic bronchopulmonary aspergillosis can present as cough variant asthma. Identification of exacerbating factors such as sources of Aspergillus fumigatus are important in management.

Aged↗

Hypersensitivity pneumonitis in a raptor handler and a wild bird fancier.

BACKGROUND: Hypersensitivity pneumonitis has been associated with a variety of antigens in various settings. We have recently encountered one case of hypersensitivity pneumonitis from owl droppings and another case from a wild Moluccan cockatoo. OBJECTIVE: It is important to alert physicians to the possibility of hypersensitivity pneumonitis when dealing with wildlife workers and wild bird fanciers. METHOD: A report of two cases with progress and response to therapy. RESULTS: Clinical and serologic information are of value in the diagnosis of hypersensitivity pneumonitis due to birds and avoidance is the optimal approach. CONCLUSION: There are many raptor handlers and wild bird fanciers across the United States and the world. Given the incidence of hypersensitivity pneumonitis in pigeon breeders, this may herald a new variant of allergic disease among wildlife workers and wild bird fanciers.

Adult↗

Human tissue retrieval at post-mortem for musculoskeletal research.

Laboratory experimentation must attempt to reduce animal involvement, and human cadaveric tissue can be a suitable alternative; however, this tissue is a potential biohazard, with the transmission of human immunodeficiency and hepatitis viruses presenting a very serious problem. In this paper we discuss how human tissue can be obtained at hospital post-mortem, and how it can then be stored and handled in a laboratory environment, focusing particularly on safety issues. We discuss the way in which the Department of Orthopaedic Surgery at Leicester University obtained human tissue for research into hip replacement. It is hoped that the article will serve as a 'blue-print' for other related research projects, where human tissue is required for experimentation.

Autopsy↗

Allergic bronchopulmonary aspergillosis: serologic update for 1995.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex disease occurring in 1-2% of patients with asthma involving hypersensitivity to Aspergillus species. The diagnosis is made correlating clinical history and supporting serologic tests. Over many years various serologic tests have been used to both diagnose and follow disease activity. Initial serology from patients with all four positive tests (total serum IgE, IgE and IgG antibody indices, serum precipitins to Aspergillus fumigatus) were compared with the patients' most recent serology. The total serum IgE, IgE antibody index and serum precipitins had the most initial positive tests which stayed positive throughout treatment. The IgG antibody index was the most inconsistent. There were no significant differences between all four tests. We concluded that all four serologic tests are important in the diagnosis of ABPA.

Antibodies, Fungal↗

Comparative studies of UV-induced DNA cleavage by structural isomers of an iodinated DNA ligand.

PURPOSE: To evaluate the importance of the position of the halogen atom in iodinated DNA-binding bibenzimidazoles, with respect to sensitization of UV-A-induced DNA breakage. METHODS AND MATERIALS: Three analogues of iodoHoechst 33258, denoted ortho-, meta- and paraiodoHoechst, according to the site of iodine substitution, were synthesized. Plasmid DNA (pBR322) was used to assay UV-A-induced DNA single-strand breaks (ssbs). The location of the sites of strand breakage was determined by DNA sequencing gel analysis, using a 32P-endlabelled oligoDNA with a single binding site for the ligands. RESULTS: A clear trend in decreasing activity of sensitization of UV-induced DNA ssbs was established: ortho- > meta-, para- > iodoHoechst 33258. The sequencing gel studies showed that orthoiodoHoechst was distinct from the other three compounds, with respect to the sites of DNA strand breakage and the chemistry of the cleavage reaction. CONCLUSION: The position of iodine substitution in iodinated bibenzimidazoles determines the location of the carbon-centered radical on the ligand in the minor groove of DNA. DNA strand cleavage is mediated by abstraction of a nearby deoxyribosyl H-atom. Hence, the position of the radical species determines: which deoxyribosyl group is attacked (i.e., site of cleavage relative to the ligand binding site); which H-atom is abstracted, more specifically which of the five deoxyribosyl carbons is involved (i.e., the chemistry of the cleavage reaction), and the stereochemistry of the transition state for the H-atom abstraction (and hence the efficiency or extent of strand breakage). The ortho-compound represents the best example to date of iodinated DNA ligands designed as potential radiation sensitizers, as an extension of the well-established sensitization by halogenated DNA precursors.

Base Sequence↗

HLA class I gene, antigen and haplotype frequencies in New Zealand Maori and Europeans.

AIM: To determine class I HLA gene, antigen and haplotype frequencies for New Zealand Maori and Europeans. METHODS: Statistical analysis was performed using accumulated data from Maori (n = 576) and European (n = 1747) parentage studies. RESULTS: HLA class I gene, antigen and haplotype frequencies are as tabulated. Significant statistical differences were shown to exist between New Zealand Maori, New Zealand Europeans and Europeans. Gene frequencies of HLA A1, 3, 9, 11, 19 and HLA B7, 8, 12, 16, 22, and 40 differed significantly between New Zealand Maori and New Zealand European data. Gene frequencies of HLA A1 and B12 differed significantly between New Zealand European and European data. CONCLUSIONS: This HLA frequency data can be used for calculating more reliable indices of paternity or for determining the potential availability of matched organs for transplantation, as well as for anthropological studies. The data may also be useful in forensic investigations.

Europe↗

Serum factor in Miller-Fisher variant of Guillain-Barré syndrome and neurotransmitter release.

Serum IgG autoantibodies to GQ1b ganglioside are associated with the acute phase of the Miller-Fisher syndrome (MFS). We investigated the effects of three anti-GQ1b-positive MFS sera in the mouse phrenic-nerve/diaphragm preparation. Miniature endplate potential frequencies increased eight-fold within 25 min, declined rapidly, and ceased altogether after 3 h, when nerve stimulation no longer evoked a response. One MFS convalescent serum (anti-GQ1b negative) and sera from healthy controls and from patients with other neurological diseases were without effect. Thus muscle weakness in MFS may be caused by a serum factor, likely to be GQ1b antibody, that leads to failure of acetylcholine release from motor nerve terminals.

Autoantibodies↗

Phosphate transport in osteoblasts from normal and X-linked hypophosphatemic mice.

Human hypophophatemic vitamin D-resistant rickets (X-linked hypophosphatemia-XLH) is characterized by hypophosphatemia, a decreased tubular reabsorption of phosphate (P(i)) and defective skeleton mineralization. Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent phosphate transport in isolated osteoblasts derived from the calvaria of normophosphatemic and hypophosphatemic mice. Initial rates of phosphate uptake by normal and Hyp osteoblasts showed similar slopes. Osteoblasts from both normal and Hyp mice exhibited saturable, sodium-dependent phosphate transport with apparent Vmax and Km values not significantly different (normal mice, Vmax = 24.30 +/- 3.45 nmol/mg prot. 10 min, Km = 349.49 +/- 95.20 mumol/liter; Hyp mice, Vmax = 23.03 +/- 3.41 nmol/mg prot. 10 min, Km = 453.64 +/- 106.93 mumol/liter, n = 24). No differences were found in the ability of normal and Hyp osteoblasts to respond to P(i) transport after 5 hours of P(i) deprivation. Both cell types exhibited a similar increase in cAMP in response to PTH. The accumulated results demonstrate that P(i) uptake and transport in normal and Hyp mouse osteoblasts is a sodium-dependent saturable process. As osteoblast P(i) uptake and transport is apparently normal in the Hyp mouse model of XLH, the "osteoblastic failure" described for the Hyp mouse should be attributed to other mechanism(s).

Animals↗

Dendritic cells from HIV-1 infected individuals show reduced capacity to stimulate autologous T-cell proliferation.

Dendritic cells (DC) exposed for a short period of time (1 day) in vitro to HIV infection caused stimulation of autologous T-cells, but those exposed for a longer period (3 days) before addition to T-cells stimulate little or no proliferation [1]. Since a proportion of DC from patients who are HIV-1 seropositive is infected with HIV-1 [2] we used the same culture system to test the level of ongoing stimulation of autologous T-cells by DC. The DC from patients with HIV-1 infection showed no enhanced stimulation of autologous T-cells; they produced significantly lower levels of proliferation than those induced by DC from normal controls or from high risk seronegative individuals. However, DC stimulated production of antibodies to gp120 and p24 in cultures containing autologous B plus T-cell in the absence of any added exogenous antigens as previously described [3]. DC in asymptomatic individuals thus appear to be fuelling antibody production but not T-cell proliferation. The results suggest that a failure by DC to stimulate T-cell proliferation either to HIV-1 or to other environmental antigens may be involved in the failure of cell-mediated responses in HIV infection.

Cells, Cultured↗

The population dynamics of parasitic helminth communities.

This paper describes a mathematical model which allows us to compare the data collected from short-term cross-sectional surveys with the population dynamics of host and parasite populations over longer periods of time. The model extends an earlier framework for two parasite species in one host, to one for an arbitrary number of parasite species. We show that the conditions necessary for the coexistence of two parasite species extend to expressions for the coexistence of three or more parasite species. Furthermore, the model suggests that those species which form the 'core' of the parasite community are those whose high fecundity and transmission efficiency permit them to colonize hosts readily. In contrast, those species which are classified as 'satellite' species of the community are either species with low fecundity, or low transmission efficiencies. This work confirms earlier studies that suggest that increasing degrees of aggregation are crucial in allowing several species of parasites to coexist in the same species of hosts. The properties of the model are compared with patterns observed in data collected for helminth parasites of Anolis lizards, wood mice and eels. This combined theoretical and empirical approach confirms the importance of the life history strategies of the parasite in determining the abundance of each species in the community. It suggests that studies of parasite community structure have to pay more attention to the strategies pursued by each individual species before interactions between species are considered.

Animals↗

Comparative studies of UV-induced DNA cleavage by analogues of iodoHoechst 33258.

Following the earlier demonstration that iodo-Hoechst 33258 sensitizes DNA and cells to UVA, presumably mediated by formation of a carbon-centred radical on the ligand upon dehalogenation, three isomeric analogues of iodo-Hoechst 33258 have now been studied. The isomers differ in the location of the iodine atom in the phenyl ring of the ligand, relative to the site of attachment of the bibenzimidazole moiety, and are accordingly denoted ortho-, meta- and para-iodoHoechst. Comparison of the ligands with respect to induction of DNA ssb in pBR322 DNA revealed a wide range of activity; (D37's vary by a factor of 37), decreasing in the order: ortho- > meta- and para- > iodoHoechst 33258. Preliminary dehalogenation studies suggest that the higher activity of the ortho isomer results more from increased cross-section for dehalogenation than from increased efficiency of strand breakage per dehalogenation event. However, the chemistry of strand breakage by the ortho-isomer is distinctive, and tentatively assigned to initial attack at the 1'-deoxyribosyl carbon; the other two isomers, like iodo-Hoechst 33258, attack the 5'-carbon. The results are discussed in terms of the spectrum of DNA strand breakage chemistry associated with ionizing radiation, and the potential of DNA strand breaking agents such as the iodoHoechst compounds to study the chemical and biological consequences of the different subclasses of initial DNA damage.

Base Sequence↗

The pattern of diagnosed HIV infection in Australia, 1984-1992.

OBJECTIVE: To describe the pattern of newly diagnosed HIV infection in Australia, between 1984 and 1992. METHODS: State and Territory health authorities reported cases of newly diagnosed HIV infection to the national HIV surveillance centre. Information sought on each case included the State or Territory of diagnosis, the case identifying number, the sex, date of birth and postcode of residence of the person with newly diagnosed HIV infection, the source of exposure to HIV and the date of specimen collection for the diagnosis of infection. RESULTS: By the end of December 1992, a total of 16,765 cases of newly diagnosed HIV infection had been reported in Australia. The annual number of cases declined between 1985 and 1992. Most diagnoses were among males, and exposure to HIV was attributed to male homosexual contact for more than 80% of cases for which information on exposure to HIV was available. Cases of HIV infection attributed to heterosexual contact represented an increasing proportion of the annual number of diagnoses over the period 1985-1992, among both men and women. CONCLUSION: National surveillance for newly diagnosed HIV infection has complemented national surveillance for diagnoses of AIDS as a key mechanism for monitoring the course of the HIV epidemic in Australia. The pattern of newly diagnosed HIV infection was similar to the pattern of AIDS diagnoses, with the overwhelming majority of diagnoses of infection being in adult males whose exposure to HIV was attributed to homosexual contact. Limitations of HIV surveillance include the lack of information on HIV testing patterns, incomplete information on HIV exposure histories and duplication of reported diagnoses.

Adolescent↗

Expression of the Bordetella pertussis P.69 pertactin adhesin in Escherichia coli: fate of the carboxy-terminal domain.

The mature pertactin protein (P.69) of Bordetella pertussis can be isolated from the bacterial cell surface as a polypeptide with an apparent molecular mass of 69,000 Da as determined by sodium dodecyl sulphate gel electrophoresis. However the open reading frame of prn, the pertactin gene, encodes a polypeptide with a predicted molecular mass of 93,478 Da, referred to as P.93. Expression of the prn gene in Escherichia coli leads to the synthesis of the full-length P.93 polypeptide, which is rapidly processed to the mature P.69 protein located at the cell surface. The P.93 precursor polypeptide is processed at both termini. A 34 amino acid long signal sequence is removed from the amino-terminus and a polypeptide sequence of about 30,000 Da (P.30) is cleaved from the carboxy-terminus. Deletion of the 3' region of prn, encoding P.30, results in the expression of an intracellular form of P.69. Antiserum which recognizes P.30 was raised using synthetic peptides based on the primary amino acid sequence of the region. This anti-P.30 serum was used in a Western blot analysis of fractionated cells of B. pertussis and E. coli harbouring the intact prn gene. The P.30 polypeptide was readily detected in outer membrane fractions prepared from both of these bacterial species, although it could not be shown to be exposed at the cell surface.

Amino Acid Sequence↗