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Biomedical subjects

M Farrington

Publications and source records attributed to M Farrington.

At least 55 records · Page 3Linked to original sources
PubMed1993

The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome.

The prominent role of the CD40 receptor in B cell responses led us to investigate the role of the gp39-CD40 interaction in a group of primary immunodeficient patients with defective antibody production. Here we report that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction. B cells from HIM patients express functional CD40, but their T cells do not bind CD40-Ig. These patients expressed normal levels of gp39 mRNA, but these mRNAs encode defective gp39 proteins owing to mutations in the extracellular domain of gp39. Soluble recombinant forms of gp39 containing these mutations were unable to bind CD40 and drive normal B cell proliferation. The gene encoding gp39 was mapped to Xq26, the X chromosome region where the gene responsible for HIM had previously been mapped. These data suggest that a defect in gp39 is the basis of X-linked HIM.

Adolescent↗
PubMed1993

Development of an internal quality assessment scheme in a clinical bacteriology laboratory.

AIM: To develop an internal quality assessment (IQA) scheme in a clinical bacteriology laboratory. METHODS: Over 24 months, 1230 diagnostic specimens, representing 0.42% of laboratory workload, were anonymised and resubmitted for analysis. Six hundred and twenty one (48.7%) of these gave positive culture results; 44 fecal and upper respiratory specimens were "spiked" (artificially inoculated) to increase the proportion of positive samples. RESULTS: Discrepancies between IQA and clinical sample results occurred in 188 cases (14.8%): 76.6% of these were in culture results, 13.3% in microscopy performance, and 10.1% in clerical recording. The culture discrepancy rate for each positive sample was lowest for wound (17.5%) and urine (18.1%) specimens, and highest for faeces (34.9%) and upper respiratory (37.7%) samples. Discrepancies in several areas responded to staff training and improvement in technical methods. CONCLUSIONS: An IQA programme of this type assesses the reproducibility of tests within a diagnostic laboratory when analysing common specimen types and organisms. It permits blind assessment of many areas of diagnostic work that are not readily amenable to other quality assurance methods, and it raises the awareness of all staff to the importance of quality in every aspect of specimen and data processing.

Bacteriological Techniques↗
PubMed1993

Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin.

Most patients with common variable immunodeficiency (CVI) have normal numbers of circulating B cells but low concentrations of serum Ig. To determine if the hypogammaglobulinemia is caused by an intrinsic B cell defect, we studied B cell function of 22 CVI patients. Cultured B cells from all CVI patients underwent normal proliferation and synthesized normal quantities of IgE in the presence of anti-CD40 and IL-4. If cultured with anti-CD40 and IL-10, four patterns of Ig isotype synthesis were observed. Six CVI patients produced normal amounts of IgM, IgG, and IgA. Four patients produced normal quantities of IgM and IgG. Of the remaining 12 patients who failed to synthesize IgG and IgA, 8 produced normal and 4 synthesized decreased amounts of IgM. Analysis of the IgG subclasses produced by 10 patients with IgG-secreting B cells revealed that IgG4 was the most affected subclass, followed by IgG2; synthesis of IgG3 and IgG1 remained normal. Similarly, in the six IgA producing patients, IgA2 was more often affected than IgA1. The hierarchy of Ig isotype and subclass synthesis corresponds to Ig heavy chain constant region gene location on chromosome 14. Thus, circulating B cells of CVI patients are committed to synthesize one or more Ig isotypes or subclasses, and under proper conditions can proliferate, mature into Ig-secreting cells, and undergo class switch to IgE.

Adolescent↗
PubMed1993

Regulation of antibody responses: the role of complement and adhesion molecules.

To analyze the importance of cell surface-associated molecules in modulating the immune response by facilitating T/B cell interaction, we used the T cell-dependent antigen, bacteriophage phi X174. Taking advantage of "experiments of nature", we studied specific antibody synthesis in patients with deficiencies of complement components or of the adhesion molecule CD11/CD18 (leukocyte adhesion defect, LAD) and guinea pigs and dogs with early complement component deficiency. Following intravenous injection of bacteriophage phi X174 into normal subjects or animals, a primary response consisting of IgM, a secondary response consisting of IgM and IgG, and a tertiary, predominantly IgG response can be distinguished. Patients and guinea pigs deficient of early complement component and LAD patients responded to repeated phage immunization with depressed antibody titers, lack of or inadequate amplification, and failure to switch from IgM to IgG, suggesting a defect in generating antigen-specific memory cells. Several mechanisms have to be considered: (i) The complement portion of the antigen-antibody complement complex facilitates the accumulation and trapping of antigen in lymphoid organs, thus improving the response to Ag at low concentrations. (ii) Immune complexes preferentially bind to antigen-specific B cells, cells expressing Fc receptors, or CR2 and CR3, the receptors for C3bi. (iii) The weak binding established between the MHC-II/Ag complex and the TCR complex is strengthened through the binding of several adhesion molecule pairs. (iv) Receptor-ligand binding initiates activation signals. The concept of binding/signaling via interacting molecules is further supported by the observation that mAb 60.3, recognizing the beta chain of CD11/CD18, blocks in vitro synthesis of antibody to bacteriophage by primed PBMC.

Animals↗
PubMed1992

Resistance to desiccation and skin fatty acids in outbreak strains of methicillin-resistant Staphylococcus aureus.

Resistance to desiccation and to skin fatty acids was measured in three groups of methicillin-resistant Staphylococcus aureus (MRSA) strains and a group of control strains. Organisms from a large outbreak on a special care baby unit (SCBU), where MRSA had been isolated from staff hands but not from the environment, were significantly more sensitive to drying than strains from a burns unit where extensive environmental contamination had been demonstrated. MRSA from other wards, in the same hospital but not associated with large outbreaks, gave heterogeneous results. Fatty-acid resistance, determined by an agar dilution method, was not associated with strain origin. Some epidemic strains of MRSA were relatively sensitive to desiccation, and the abilities of such strains to spread widely on a SCBU by the hand-borne route could not be explained by enhanced resistance to skin fatty acids.

Cross Infection↗
PubMed1991

Neurogenesis in the brain auditory pathway of a marsupial, the northern native cat (Dasyurus hallucatus).

Neurogenesis in the auditory pathway of the marsupial Dasyurus hallucatus was studied. Intraperitoneal injections of tritiated thymidine (20-40 microCi) were made into pouch-young varying from 1 to 56 days pouch-life. Animals were killed as adults and brain sections were prepared for autoradiography and counterstained with a Nissl stain. Neurons in the ventral cochlear nucleus were generated prior to 3 days pouch-life, in the superior olive at 5-7 days, and in the dorsal cochlear nucleus over a prolonged period. Inferior collicular neurogenesis lagged behind that in the medial geniculate, the latter taking place between days 3 and 9 and the former between days 7 and 22. Neurogenesis began in the auditory cortex on day 9 and was completed by about day 42. Thus neurogenesis was complete in the medullary auditory nuclei before that in the midbrain commenced, and in the medial geniculate before that in the auditory cortex commenced. The time course of neurogenesis in the auditory pathway of the native cat was very similar to that in another marsupial, the brushtail possum. For both, neurogenesis occurred earlier than in eutherian mammals of a similar size but was more protracted.

Aging↗
PubMed1991

Antigen detection in pneumococcal pneumonia.

Streptococcus pneumoniae remains the commonest proven cause of community-acquired pneumonia in patients admitted to hospital, but no currently available diagnostic method can be regarded as a gold standard. Microscopy of sputum is usually considered insensitive and poorly specific, and more invasively-obtained specimens are not routinely collected. Cultures of blood and respiratory secretions, and countercurrent immunoelectrophoresis (CIE) and particle agglutination-based assays for capsular polysaccharides in serum and urine specimens, are specific but less than ideally sensitive. Some workers have reported specificity problems when immunoassays are applied to respiratory secretions. New diagnostic methods include detection of pneumococcal C polysaccharide in sputum and urine by ELISA and particle-agglutination assays, and these appear promisingly sensitive and specific in preliminary studies. Clinical assessments are now required to define the role of these techniques in guiding the treatment of individual patients.

Adult↗
PubMed1991

Streptococci from primary isolation plates grouped by reverse passive haemagglutination.

Reverse passive haemagglutination, a novel microtitre based assay, was compared with the Streptex (Wellcome UK) latex slide agglutination kit for streptococcal grouping in a diagnostic microbiology laboratory. Three hundred and fifty two extracts from 349 consecutive primary isolation plates were assayed by both methods. Reverse passive haemagglutination gave identical grouping results for 98.0% of the 345 streptococci identified by Streptex, and the kappa coefficient of agreement between the methods for all 352 extracts tested was 0.973. Cross reactions with Listeria spp seen with Streptex were not found by reverse passive haemagglutination. In the reverse passive haemagglutination method 11 streptococci could be grouped on each 96-well plate and most reactions were stable for at least 30 minutes. Reverse passive haemagglutination is more rapid to perform than latex slide agglutination when many organisms are to be grouped, and the patterns of haemagglutination are easily recognised. If the method was taken into routine use in a diagnostic laboratory, the persistence of reverse passive haemagglutination reactions would enable grouping results to be checked for quality control purposes.

Genitalia↗
PubMed1991

A microbiological hazard in caloric testing.

The use of caloric testing is widespread in hospital audiology departments. This paper describes contamination of the caloric water tanks with the organism Acinetobacter anitratus and the changes in practice instituted to eliminate this risk to patients.

Acinetobacter↗
PubMed1990

Outbreaks of infection with methicillin-resistant Staphylococcus aureus on neonatal and burns units of a new hospital.

Multiple introductions of methicillin-resistant Staphylococcus aureus (MRSA) strains occurred to a new hospital in Hong Kong. Two years of clinical microbiological surveillance of the resulting outbreaks was combined with laboratory investigation by phage and antibiogram typing, and plasmid profiling. The outbreaks on the special care baby (SCBU) and burns (BU) units were studied in detail, and colonization of staff and contamination of the environment were investigated. MRSA were spread by the hands of staff on the SCBU, where long-term colonization of dermatitis was important, but were probably transmitted on the BU by a combination of the airborne, transient hand-borne and environmental routes. Simple control measures to restrict hand-borne spread on the SCBU were highly effective, but control was not successful on the BU.

Burn Units↗
PubMed1990

Therapy: the microbiologist's view.

Potentially, the clinical microbiologist is able to influence empirical and definitive therapy of bacteraemia. Definitive therapy of the individual can only be affected after the results of routine culture and sensitivity tests are available. Some so-called 'rapid' laboratory techniques enable early identification and sensitivity testing of isolates from blood cultures. Empirical therapy is more difficult to influence, with microbiologists relying on epidemiologically based education of the prescriber or encouragement of him to seek advice at an early stage. Newer, truly rapid methods that do not rely on culture may come to have an impact on individual empirical therapy. Microbiologists acquire information upon which to base their recommendations by a variety of local surveillance measures, from the published literature and (particularly for organisms of infection control significance) through professional contacts with their colleagues in other hospitals. Influence may be exerted on clinicians by direct contact, through manipulation of the content of laboratory reports, or by regular circulation of locally-collected summary data. The assessment of the real impact on bacteraemia of blood culture techniques and microbiological advice is in its infancy, but new data collection and handling methods make this an achievable ideal.

Culture Media↗
PubMed1990

Growth hormone aggregates in the rat adenohypophysis.

Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro.

Animals↗
PubMed1987

Four documented cases of eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in Hong Kong.

4 cases of eosinophilic meningoencephalitis in Hong Kong are described. The major clinical features of the patients, who were 2-60 years old, were low grade fever, headache, mild meningeal signs, right facial palsy or hemiplegia. Eosinophilia in the peripheral blood and eosinophilic pleocytosis were prominent. Computerized tomography scans of brain showed a small area of attenuation with surrounding hypodense area; the lesion was resolved 1-2 months after admission to hospital. Electroencephalograms revealed abnormally slow dysrhythmia. Sections of a nematode observed in the brain of a patient who died were identified as those of young adult Angiostrongylus cantonensis. High ELISA titres against the crude antigens of this nematode were also noted in the serum of 3 patients. The disease is probably under-recognized in Hong Kong.

Adult↗