Ophthalmological screening for CMV retinitis in HIV infection.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
S Young
Publications and source records attributed to S Young.
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↗
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↗
Flash-photolysis studies of the electron transfer from genetically modified spinach plastocyanin to photosystem I.
Plastocyanin (Pc) has been modified by site-directed mutagenesis at two separate electron-transfer (ET) sites: Leu-12-Glu at a hydrophobic patch, and Tyr-83-His at an acidic patch. The reduction potential at pH 7.5 is decreased by 26 mV in Pc(Leu-12-Glu) and increased by 35 mV in Pc(Tyr-83-His). The latter mutant shows a 2-fold slower intracomplex ET to photosystem I (PSI) as expected from the decreased driving force. The affinity for PSI is unaffected for this mutant but is drastically decreased for Pc(Leu-12-Glu). It is concluded that the hydrophobic patch is more important for the ET to PSI.
Electron Spin Resonance Spectroscopy↗
Possible transmission of Mycobacterium leprae in a group of UK leprosy contacts.
A case of infectious leprosy in residential accommodation in the UK prompted a study of the cellular and humoral response to Mycobacterium leprae in two groups of individuals who were in contact with the index case for almost a year. In the younger staff group (mean age 44 years) 23 of 30 individuals had positive Mitsuda skin tests, 25 showed lymphocyte transformation to a soluble sonciate of M leprae and 2 had slightly raised IgM antibody concentrations to the terminal disaccharide of M leprae phenolic glycolipid-1. In the older group of residents (mean age 83 years) 7 of 36 individuals were skin-test positive, 25 of 33 were positive by lymphocyte transformation, but none had raised antibody levels. When retested on two further occasions, the same 2 individuals in the younger group still had raised antibody concentrations, 1 of whom had a persistent lepromin skin-test response for over 8 months and showed a pronounced increase in lymphocyte transformation to mycobacterial antigens. The findings suggest that transmission of M leprae may have occurred in these 2 contacts, who were therefore given 6 months' chemoprophylaxis with rifampicin.
Adult↗
Purification and characterization of biologically active scatter factor from ras-transformed NIH 3T3 conditioned medium.
Scatter factor (SF), a glycoprotein produced by cultured fibroblasts, acts in vitro on epithelial cells causing separation and increased local motility. In this study, the polypeptide was purified to apparent homogeneity in high yields with conserved biological activity from medium conditioned by ras-transformed NIH 3T3 cells, by a three-step procedure involving ammonium sulphate fractionation, cation-exchange and hydroxyapatite chromatography. After purification, SF specific activity increased from approximately 0.3 units/microgram in unprocessed conditioned medium to approximately 5 units/ng, and cumulative recovery of biological activity was approximately 38%. Treatment of pure SF with N-glycanase resulted in a decreased Mr, but no concomitant effect was observed on biological activity. Proteolytic activity was absent from samples of both partially purified and pure SF. Our biochemical studies showed that SF, which is highly aggregated in low-ionic-strength media, is not aggregated in 0.4 M-salt. Under non-reducing conditions, pure SF migrated as a single stained band at Mr 67,000 on SDS/PAGE, and biological activity was eluted from unstained gels with an identical Mr. SF was electrofocused sharply at pI 8.5 with no degradation of activity. From ultracentrifugation studies (under non-aggregating conditions), the sedimentation coefficient of active SF was 3.7 S and f.p.l.c. molecular sieve chromatography indicated a Stokes' radius of 2.95 nm. The calculated Mr from these data was 61,400. The appearance of three stained polypeptides of Mr 82,000, 57,000 and 32,000 derived from the Mr-67,000 constituent after reduction with mercaptoethanol suggests that SF may be a heterodimer of Mr-57,000 and -32,000 subunits. Data from protein sequence analysis of the hydroxyapatite-purified protein confirms that SF has sequence identity with both rat hepatocyte growth factor and human fibroblast tumour cytotoxic factor.
Amidohydrolases↗
Immunoglobulin variable-region-like domains of diverse sequence within the major histocompatibility complex of the chicken.
The highly polymorphic B-G antigens are considered to be part of the major histocompatibility complex (MHC) of the chicken, the B system of histocompatibility, because they are encoded in a family of genes tightly linked with the genes encoding MHC class I and class II antigens. To better understand these unusual MHC antigens, full-length B-G cDNA clones were isolated from B21 embryonic erythroid cell cDNA library, restriction-mapped, and sequenced. Five transcript types were identified. Analysis of the deduced amino acid sequences suggests that the B-G polypeptides are composed of single extracellular domains that resemble immunoglobulin domains of the variable-region (V) type, single membrane-spanning domains typical of integral membrane proteins, and long cytoplasmic tails. Sequence diversity among the five transcript types was found in all domains, notably including the B-G immunoglobulin V-like domains. The cytoplasmic tails of the B-G antigens are made up entirely of units of seven amino acid residues (heptads) that are typical of an alpha-helical coiled-coil conformation. The heptads vary in number and sequence between the different transcripts. The presence within B-G polypeptides of polymorphic immunoglobulin V-like domains warrants further investigations to determine the degree and nature of variability within this domain in these unusual MHC antigens.
Amino Acid Sequence↗
Hybridization and dissociation rates of phosphodiester or modified oligodeoxynucleotides with RNA at near-physiological conditions.
We have used RNase H to study both the rates of oligonucleotide hybridization and dissociation at near-physiological conditions. We have studied the Effects of oligonucleotide length, mismatch, and chemical modifications on oligonucleotide association and dissociation with RNA. Dissociation results were compared with standard thermal melting curves to compare relative stabilities evaluated by the two techniques. Although generally the two techniques correlate for the compounds evaluated, we found several instances where the thermal melting curves failed to reflect the relative stability of different oligonucleotides at 37 degrees C using near-physiological conditions. This study suggests that direct measurement of hybridization and dissociation of an oligomer with RNA more accurately assesses the complicated kinetic scheme at 37 degrees C using near-physiological conditions than thermal melting curves would predict.
Base Sequence↗
The influence of a family history of asthma and parental smoking on airway responsiveness in early infancy.
BACKGROUND: Airway responsiveness to inhaled nonspecific bronchoconstrictive agents has been demonstrated in normal, healthy infants. However, it is unknown whether airway responsiveness is present from birth or if it develops as a result of subsequent insults to the respiratory tract. To investigate this question, we assessed airway responsiveness in 63 normal infants at a mean age of 4 1/2 weeks. METHODS: Respiratory function was measured with use of the partial forced expiratory flow-volume technique to determine the maximal flow at functional residual capacity (VmaxFRC). The infants inhaled nebulized histamine at sequentially doubled concentrations (0.125 to 8.0 g per liter), until a concentration was reached at which the VmaxFRC fell by 40 percent from the base-line value (PC40) or until a concentration of 8.0 g per liter was reached. We also assessed maternal serum levels of IgE, cord-serum levels of IgE, the infants' skin reactivity to several allergens, and the parents' responsiveness to histamine and obtained family histories of asthma and smoking. RESULTS: Airway responsiveness was increased in infants with a family history of asthma (n = 19; median PC40, 0.78 g per liter; 95 percent confidence interval, 0.44 to 1.15; P less than 0.01), parental smoking (n = 13; median PC40, 0.52 g per liter; 95 percent confidence interval, 0.43 to 5.40; P less than 0.05), or both (n = 20; median PC40, 0.69 g per liter; 95 percent confidence interval, 0.37 to 2.10; P less than 0.05), as compared with the infants with no family history of asthma or smoking. The infants with no family history of asthma or smoking had a median PC40 of 2.75 g per liter (95 percent confidence interval, 1.48 to 4.00). No significant relations were detected between the immunologic variables and the PC40 in the infants. CONCLUSIONS: This study indicates that airway responsiveness can be present early in life and suggests that a family history of asthma or parental smoking contributes to elevated levels of airway responsiveness at an early age.
Asthma↗
Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction. TAMI Study Group.
Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction.
Angioplasty, Balloon, Coronary↗
Coughing can relieve or exacerbate symptoms in asthmatic patients.
From about 1190 to the present day opposing views have been expressed about the effects of coughing in patients with asthma. Some accounts have stated that it brought relief and others that it exacerbated asthma, whereas others thought that it could have both effects. In the present investigation, 187 patients with a clinical diagnosis of asthma were asked whether coughing relieved or exacerbated their asthma. In 41.7% coughing caused exacerbation, in 29.9% it brought relief, in 9.9% it had no effect, and in the remaining 18.7% it sometimes exacerbated their symptoms and sometimes brought relief. When asthma was exacerbated, the most common symptom induced was breathlessness, and then wheezing; chest tightness was the least frequent. When coughing brought relief it was mainly through the expectoration of sputum. However, a small proportion of patients found relief even if there was no expectoration. If coughing exacerbates asthma and persists in the face of treatment with standard medication, then treatment specifically directed at its diminution could reduce morbity considerably.
Asthma↗
Seasonally recurrent granuloma annulare of the elbows.
Granuloma annulare may be recurrent and various precipitating factors have been described but seasonal cases have not been previously reported. We describe two patients with granuloma annulare on the elbows which developed in spring and resolved spontaneously in October each year. We believe that this type of seasonally recurrent granuloma annulae has not been previously described.
Adult↗
A prospective randomised trial of cyclosporin and methotrexate versus cyclosporin, methotrexate and prednisolone for prevention of graft-versus-host disease after HLA-identical sibling marrow transplantation for haematological malignancy.
A prospective randomised trial was performed in patients given HLA-identical sibling bone marrow transplants for haematological malignancy comparing the combination of cyclosporin and methotrexate (CM) (n = 20) with the combination of cyclosporin, methotrexate and prednisolone (CMP) (n = 21) as prophylaxis for graft-versus-host disease (GVHD). There was no significant differences between the two arms for the incidence of acute GVHD grades I-IV, acute GVHD grades II-IV, chronic GVHD, interstitial pneumonitis, relapse, survival and disease-free survival. The actuarial incidence of acute GVHD grades II-IV in the CMP group was 10% and in the CM group 15% (ns). The incidence of leukaemic relapse in good risk patients was 42% in the CMP group and 40% in the CM group (ns), although the majority of these relapses were cytogenetic relapses only in patients with chronic myeloid leukaemia. The incidence of acute GVHD grades II-IV in both arms of the current trial was significantly lower than in our previous trial comparing cyclosporin and methotrexate as single agents. Leukaemic relapse is now the principal cause of treatment failure in this patient population. We conclude that prednisolone should not be included as part of the prophylactic GVHD regime and that further improvement in therapeutic outcome is dependent upon better control of the underlying malignancy.
Actuarial Analysis↗
Screening for diabetic retinopathy.
There is a need for greater educational emphasis, both at undergraduate and postgraduate level, on the detection of diabetic eye disease, in particular diabetic retinopathy. The early diagnosis of the sight-threatening lesions of proliferative retinopathy and maculopathy is a prerequisite for the prevention or reduction of the visual loss and blindness associated with this diabetic complication. It is also essential that patients are aware that diabetes can result in visual loss due to diabetic retinopathy. Patients should understand that diabetic retinopathy may be present without ophthalmic or diabetic symptoms and that its incidence increases with duration of diabetes, poor diabetes control, and hypertension. They must also be aware that, if detected early, retinopathy can be treated successfully and vision preserved. Early detection depends on regular eye examination involving both visual acuity assessment and ophthalmoscopy through dilated pupils by experienced personnel. A comprehensive programme of screening followed by prompt and adequate treatment would made a significant contribution to eradicating diabetic retinopathy as a cause of blindness.
Adult↗
Bronchial responsiveness and lung function in recurrently wheezy infants.
Although most wheezy infants are considered asthmatic, they generally respond poorly to antiasthma treatment, and there is inadequate knowledge about the pathologic mechanisms that cause wheezing at this age. The aim of this study was to determine whether the strong association between wheezing and bronchial responsiveness (BR) seen in older subjects was also present in infants. We compared BR with inhaled histamine in 19 recurrently wheezy infants with a group of age-, height-, weight-, and sex-matched control infants. Maximal flow at FRC (VmaxFRC) was determined from partial expiratory flow-volume curves generated using the "squeeze" technique. Histamine was delivered during 1 min of tidal breathing in doubling concentrations from 0.125 g/L to a maximum of 8 g/L or until VmaxFRC fell by 40% (PC40). The median baseline VmaxFRC for the wheezy infants was 100.0 ml/s compared with 182.0 ml/s for the control infants (p less than 0.01). However, there was no significant difference in the PC40 between the two groups (2.1 versus 2.3 g/L).
Asthma↗