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Biomedical subjects

S Young

Publications and source records attributed to S Young.

At least 181 records · Page 10Linked to original sources

ERIK, a low-frequency red cell antigen of the MNS blood group system associated with Sta.

A new low-frequency red cell antigen, ERIK (MNS37), is associated with the Sta antigen of the MNS system. Four ERIK+ propositi have been identified: all are St(a+). Thirteen other St(a+) samples, including one of the Mz type, and over 200 St(a-) samples were ERIK-. In two of the propositi ERIK is associated with an abnormal trypsin-resistant M antigen; in the others it is associated with N, which is shown to be expressed weakly in one family. Immunoblotting with an antibody to an epitope common to glycophorin A (GPA) and glycophorin B (GPB) gave identical results with St(a+) ERIK+ and St(a+) ERIK- cells, revealing GPA, GPB, an abnormal structure GPSta and aggregates of these components. In the propositi with trypsin-resistant M, GPSta carries the unusual M antigen, whereas in the M-N+ERIK+ individual analysed by immunoblotting GPSta carries N. Immunoblotting with anti-Sta and anti-ERIK showed that Sta is located on GPSta but that ERIK is located on GPA, presumably the GPA molecule encoded by the GYPA gene contiguous to the gene encoding GPSta.

Adult↗

Changing results of HLA-identical sibling bone marrow transplantation in patients with haematological malignancy during the period 1981-1990.

During the years 1981-90 inclusive 227 patients with haematological malignancy received an HLA-identical sibling first transplant at St Vincent's Hospital, Sydney. Recipients with acute leukaemia in first remission or chronic myeloid leukaemia in first chronic phase were analysed as good risk, and those beyond these stages, as poor risk patients. Good risk patients transplanted in the years 1986-90 (n = 52) showed improved actuarial survival (74%) compared to those (n = 58) transplanted during 1981-85 (37%, p = 0.01). There was a suggestion that leukaemia-free survival was also improved in those transplanted during the later time period (62% versus 36%, p = 0.07). In contrast, poor risk patients transplanted during 1986-90 (n = 55) appeared to have worse leukaemia-free survival (15%) compared to those transplanted during 1981-85 (n = 62) (22%, p = 0.09). The incidence of acute graft-versus-host disease (GVHD) grades I-IV in all patients was 94% in those transplanted during 1981-85 (n = 120) and 86% in those transplanted during 1986-90 (n = 107) (p = 0.002). The incidence of acute GVHD grades II-IV was 37% during 1981-83, 20% during 1984-86, and 28% during 1987-90 (p = 0.1). The decrease in incidence and severity of acute GVHD correlated with the introduction of the cyclosporin/short methotrexate regimen in our practice. The incidence of cytomegalovirus (CMV) pneumonitis was 18% in 1981-85, and 11% in 1986-90 (p = 0.09). In 1989 and 1990 no cases of CMV pneumonitis occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Effect of salbutamol on histamine induced bronchoconstriction in healthy infants.

BACKGROUND: The effect of inhaled beta 2 adrenergic drugs on infants with wheezing disorders remains controversial. Salbutamol inhibits the bronchial responsiveness of infants to histamine and nebulised water but whether or not it acts as a bronchodilator in this age group is unclear. The aim of the present study was to determine whether salbutamol can hasten the reversal of histamine induced bronchoconstriction in infants. METHODS: Bronchial challenge with histamine was performed in 40 infants aged 12 months or less with no previous history of respiratory symptoms. Response to histamine was assessed by forced partial expiratory flow/volume curves to measure maximal flow at functional residual capacity (VmaxFRC). After a fall of 40% or more from baseline VmaxFRC, each infant was randomly assigned to receive either salbutamol 0.5% or saline 0.9% solution by nebuliser. The rate of recovery of VmaxFRC and the time to reach baseline VmaxFRC were derived by linear regression. RESULTS: Infants who received salbutamol had a significantly faster rate of recovery (geometric mean 8.5 ml/s/min) than those who received saline (4.1 ml/s/min). Considerable interindividual variation was observed in the time from maximum bronchoconstriction to recovery of baseline VmaxFRC in both groups of subjects. CONCLUSIONS: Salbutamol significantly speeds the reversal of histamine induced bronchoconstriction in infants during the first 12 months of life. This observation provides further evidence to support the presence of functional beta adrenergic receptors in the airways of infants.

Administration, Inhalation↗

Neuropathology of chronic wasting disease of mule deer (Odocoileus hemionus) and elk (Cervus elaphus nelsoni).

The pathology of the central nervous system of nine mule deer (Odocoileus hemionus) and six elk (Cervus elaphus nelsoni) with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. Lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of significant inflammatory response. Distribution and severity of lesions were evaluated at 57 locations; there were only minor differences between deer and elk. Consistent, severe lesions occurred in olfactory tubercle and cortex, hypothalamus, and the parasympathetic vagal nucleus of deer, and sections examined from these regions would be sufficient to establish a diagnosis of chronic wasting disease. Lesions were milder in these locations in elk but were sufficiently apparent to be of diagnostic value. Other differences included increased severity of lesions in some thalamic nuclei in elk in contrast to deer, the occurrence of amyloid plaques demonstrable by hematoxylin and eosin and histochemical stains in deer in contrast to elk, and the presence of mild white matter lesions in elk but not in deer. Lesions of chronic wasting disease were qualitatively comparable to those of scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy, and the human spongiform encephalopathies. Topographic distribution and lesion severity of chronic wasting disease were most similar to those of scrapie and bovine spongiform encephalopathy. Duration of clinical disease did not significantly influence lesion distribution or severity in either species.

Animals↗

A Master of Science course at the Cardiff School of Medical Photography.

Formal teaching and training in medical photography at Cardiff started in 1969 when a School of Medical Photography was established, as part of the Department of Medical Illustration, at the Cardiff Royal Infirmary. In the early 1970s the school was transferred with the Medical Illustration Department to the newly built University Hospital of Wales, and housed in planned accommodation at what is now the Institute of Health Care Studies. The school offered courses in medical photography at the level of the qualifying examinations of the Professional Institutes, to suitably qualified in-service students appointed to the Medical Illustration Department as Trainee Medical Photographers. In 1990, the University of Wales approved a Master of Science course in Medical Illustration (Photography and Video) offered by the school. The course is available both to in-service students of the school and to practising medical photographers as mature students on a distance learning programme. Details of the new course and its delivery are given.

Education, Graduate↗

Responses to gram negative enteric bacterial antigens by synovial T cells from patients with juvenile chronic arthritis: recognition of heat shock protein HSP60.

OBJECTIVE: To investigate the antigenic specificity of synovial T cells in juvenile chronic arthritis (JCA). METHODS: Synovial fluid and peripheral blood mononuclear cells from 24 patients with JCA were tested for their proliferative responses to recall antigens, enteric organisms associated with reactive arthritis, influenza A and a recombinant preparation of a mycobacterial heat shock protein, HSP65. To investigate further recognition of this last antigen, synovial T cells from one B27+ patient with pauciarticular disease were cloned using HSP65. The specificity of the resultant clones was then examined. RESULTS: Marked synovial T cell responses to enteric organisms and to HSP65 were noted, particularly in HLA-B27+, pauciarticular patients; these were similar to those seen in a B27+ patient with reactive arthritis. Responses to enteric organisms and to HSP65 were significantly correlated, suggesting recognition of an epitope common to these antigen preparations. However, all of the T cell clones obtained using HSP65 proved to recognize E. coli derived antigens contaminating the recombinant HSP65 rather than the mycobacterial antigen; these contaminants included the 60 kDa E. coli HSP, GroEL. The GroEL specific T cells did not respond to heat shocked human cells; this suggests (but does not prove) that they do not crossreact with human HSP60. CONCLUSION: Synovial T cell recognition of antigens from enteric organisms associated with reactive arthritis is a common feature in pauciarticular JCA. Among the target antigens is the GroEL HSP, but T cells recognizing this antigen do not necessarily crossreact with the homologous human HSP60.

Antigens, Bacterial↗

Postoperative pneumonia: a prospective study of risk factors and morbidity.

BACKGROUND: Postoperative pneumonia (PP) is a major complication that has been linked to microaspiration of pathogens originating in the gastrointestinal tract. This prospective study was performed to define the role of gastric bacterial aspiration in the development of PP. METHODS: Informed consent was obtained before operations from 140 veterans scheduled for major elective procedures requiring nasogastric tubes, and cultures were obtained of the gastric contents and sputum twice daily after operation. RESULTS: PP developed in 26 (18.6%) of 140 patients. The patients who had PP did not differ from those with no pneumonia after operation except for a history of chronic obstructive pulmonary disease, which was found in 38.5% of those with PP compared with 20% of patients with no pneumonia (p < 0.05). Morbidity was increased in association with PP, because length of stay in the surgical intensive care unit (6.2 vs 2.6 days), days intubated (2.7 vs 0.6), total postoperative days (15.3 vs 8.4), and mortality rates (19.2% vs 1.7%) were greater than in patients with no pneumonia. Gastric pathogens were present on entry in 38% of patients, and 32% of these had PP compared with 13% whose initial gastric cultures were sterile (p = 0.01). Colonization of sputum for greater than 24 hours with gastric pathogens occurred in 28% of patients. These patients had a 40% incidence of PP compared with 12% in patients without such evidence of microaspiration (p < 0.01). CONCLUSIONS: PP is a morbid postoperative complication associated with not only chronic obstructive pulmonary disease but also the presence of gastric bacteria during operation and transmission of gastric bacteria to the pulmonary tree after operation.

Adult↗

Cloning of ndhK from soybean chloroplasts using antibodies raised to mitochondrial complex I.

A soybean shoot cDNA expression library was screened with polyclonal antibodies raised against red beet complex I and several clones were identified. One clone, consisting of a 1 kb insert, was fully sequenced. The sequence of 1025 bp was found to contain two extended open reading frames and the proteins encoded were identified as the ndhK and ndhJ products of the chloroplast genome. Nuclear, mitochondrial and chloroplast DNA was isolated and probed with a ndhK-specific probe. The chloroplast DNA contained a single copy of the cloned insert. With nuclear DNA, positively hybridising bands of 1.2, 2.7 and 3.2 kb were observed indicating that at least one gene homologous to ndhK of the chloroplast genome, is also present in the nucleus. The mitochondrial DNA did not hybridise with the ndhK probe. Western analysis of thylakoid proteins with the mitochondrial complex I antibodies revealed several bands. It is suggested that soybean contains two copies of the ndhK gene, one, on the plastid genome, coding for a subunit of a chloroplast NAD(P)H dehydrogenase, and the other, in the nucleus, coding for a subunit of mitochondrial complex I.

Amino Acid Sequence↗

Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease.

Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigated the relationship between synaptic and dendritic abnormalities in the neocortex of Alzheimer patients and examined the extent to which these structural alterations correlate with the severity of cognitive impairment in AD. Quantitative neuroanatomical data were obtained from immunofluorescence-labeled specimens using a laser-scanning confocal microscope, computer-assisted image processing and serial section reconstruction techniques. We found that the AD cases showed a 34% loss in the number of presynaptic terminals per 100 square (sq) microns, many of which showed structural abnormalities. The AD neuropil had an average of 10 +/- 7 dendritic threads per 1,000 sq microns, with the average thread measuring 2 sq microns. Severe AD cases had thicker threads compared with mild to moderate AD cases. Three-dimensional analysis showed clustering of synapses around threads, as well as presynaptic boutons apposed to dendritic neuropil threads. Statistical analysis showed that the strongest correlation was between synapse density and Blessed score of cognitive impairment. Thread counts did not correlate with either but were correlated with tangle counts. Stepwise multiple regression analysis showed that tangle counts, but not threads, strengthened the correlation between Blessed score and synapses. We conclude that synaptic damage may precede dendritic thread and tangle formation, and that threads do not necessarily induce synaptic pathology. Instead, dendrite sprouting in the denervated regions could be associated with increased accumulation of cytoskeletal proteins observed in the dendritic threads.

Aged↗

Tissue-specific expression of the alternative oxidase in soybean and siratro.

Alternative oxidase activity (cyanide-insensitive respiration) was measured in mitochondria from the shoots, roots, and nodules of soybean (Glycine max L.) and siratro (Macroptilium atropurpureum) plants. Activity was highest in the shoots and lowest in the nodules. Alternative oxidase activity was associated with one (roots) or two (shoots) proteins between 30 and 35 kilodaltons that were detected by western blotting with a monoclonal antibody against Sauromatum guttatum alternative oxidase. No such protein was detected in nodule mitochondria. Measurements of oxygen uptake by isolated soybean root and nodule cells in the presence of cyanide and salicylhydroxamic acid indicated that alternative oxidase activity was confined to the uninfected cortex cells of the nodule. Immunoprecipitation of translation products of mRNA isolated from soybean shoots revealed a major band at 43 kilodaltons that is assumed to be the precursor of an alternative oxidase protein. This band was not seen when mRNA from nodules was treated in the same fashion. The results indicate that tissue-specific expression of the alternative oxidase occurs in soybean and siratro.

Journal Article↗

Spongiform encephalopathies in Cervidae.

The known host range of naturally-occurring transmissible spongiform encephalopathies has expanded in recent years to include wild ruminants. Chronic wasting disease (CWD) occurs in mule deer (Odocoileus hemionus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni) in Colorado and Wyoming, United States of America. These species belong to the family Cervidae. Cases have occurred primarily in captive animals but a few affected free-ranging animals have been identified. Clinical disease in both species is characterised by progressive weight loss, behavioural alterations and excessive salivation. In deer polydipsia and polyuria also commonly occur. Significant lesions are confined to the central nervous system and consist of spongiform change in grey matter, intraneuronal vacuolation, astrocytosis and amyloid plaques. Inflammatory reaction is absent. The origin of this disease is not known. In contrast to the cases of spongiform encephalopathy recognised in five species of antelope (family Bovidae) in British zoological parks, which are an extension of the current bovine spongiform encephalopathy epizootic, CWD is not the result of food-borne exposure to the infectious agent. CWD appears to be maintained within captive populations by lateral and, possibly, maternal transmission. Spongiform encephalopathies in wild ruminants are currently geographically isolated and involve relatively small numbers of animals. However, these potentially transmissible diseases could be of greater importance in the future and should be viewed with concern in the light of international movements of wild ruminants and the current expansion of the game farming and ranching industry in many parts of the world.

Animals↗

Mycobacterial 65,000 MW heat-shock protein shares a carboxy-terminal epitope with human epidermal cytokeratin 1/2.

Molecular mimicry between mycobacterial heat-shock protein (hsp) 65 and host tissue antigens have been implicated in the autoimmune pathogenesis of certain idiopathic diseases. Here, we demonstrated that two of our previously characterized monoclonal antibodies (mAb), Ne5 and Nd4 that were directed to a carboxy-terminal epitope on the mycobacterial hsp 65, specifically cross-reacted with suprabasal cytokeratin of the normal human skin. These mAb also showed similar keratin staining of hair follicle epithelia and produced no reaction with other dermal components. Both mAb strongly stained the cytoplasm of the majority of freshly isolated epidermal keratinocytes from the normal human skin. None of these mAb showed staining with human HeLa cells and with human skin fibroblasts. Immunoblotting using total keratin extract prepared from isolated epidermal keratinocytes revealed that mAb Ne5 and Nd4 specifically reacted with a molecular size of 65,000-67,000 MW keratin protein(s) and such reactivity was not observed from cytoskeletal proteins extracted from HeLa cells and skin fibroblasts. Comparison of immunoblotting reactivity with conventional anti-cytokeratin mAb further revealed that mAb Ne5/Nd4 recognized a 65,000-67,000 MW molecular-sized protein corresponding to cytokeratin 1/2 from the same keratinocyte extract as anti-cytokeratin mAb. Preincubation of mAb Ne5/Nd4 with the purified mycobacterial hsp 65 abolished this keratin cross-reactivity in both immunohistochemistry and immunoblotting. Moreover, these mAb showed no keratin staining in lesional psoriatic skin and also reacted weakly with cultured epidermal keratinocytes. Since mAb Ne5/Nd4 specifically recognized a 67,000-65,000 MW molecular-sized protein(s) derived from epidermal keratinocytes and the known characteristics of epidermal cytokeratin 1/2 appeared to be consistent with present results, we concluded that Ne5/Nd4 cross-reactive protein(s) in the human epidermis is suprabasal cytokeratin 1/2. Comparison of the previously mapped Ne5/Nd4 epitope region of amino acid residues 525-540 of the mycobacterial hsp 65 with the entire sequence of human 65,000 MW keratin revealed that a stretch of nine amino acids of the Ne5/Nd4 epitope sequence resembled certain regions of the carboxy-terminus of the human 65,000 MW keratin. This similarity of the mycobacterial hsp 65 probably contributes to the cytokeratin cross-reactive epitope. Our results presented here demonstrate direct evidence of immunological cross-reactivity between mycobacterial hsp 65 and human epidermal cytokeratin 1/2. We speculate that Ne5/Nd4 cross-reactive epitope of epidermal cytokeratins might be an important target for skin diseases.

Amino Acid Sequence↗

Quantification of Candida albicans morphology in vaginal smears.

The morphology index (Mi) of Candida albicans cells was determined by microscopic image analysis in vaginal smears from 26 patients. The morphology of the cells typically showed a broad distribution of forms, but the mean Mi was greater than 2.0 in 23/26 instances, indicating a preponderance of pseudohyphal and hyphal forms. No association could be found between Mi and the clinical assessment of signs or symptoms of Candida infection. Comparison of these 26 patients with 43 others who had Candida-positive vaginal smears but with fewer than 15 fungal cells in the smear revealed significantly lower scores for vulvovaginal symptoms among the latter.

Candida albicans↗