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Biomedical subjects

S Young

Publications and source records attributed to S Young.

At least 199 records · Page 11Linked to original sources

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↗

A medical college service for computer-generated graphics with DIY aspects.

This paper describes the setting-up and management of a computer graphics service, mainly for producing 2 x 2 inch projection slides, by a department of medical illustration within a medical school. The service has been arranged to provide a limited facility for composing original illustrations by computer and to encourage medical and scientific staff to compose their own illustrations. These are recorded on magnetic disc for review and possible adjustment by medical illustrators. Images are then output as slides or paper prints by the medical illustration department. The range of equipment and apparatus used is described and evaluated briefly. Also described are the effects of the introduction of a computer-generated graphics service on the general work of non-patient slide production in the department.

Computer Graphics↗

Congenital cyst of common bile duct: an unusual cause of obstructive jaundice.

Congenital cysts, sometimes referred to as nonparasitic biliary cysts, are not unusual findings in the liver parenchyma, but they have not been previously described in the common bile duct. This clinical report describes a 41-year-old woman with obstructive jaundice that was caused by congenital cysts. The patient had obstruction of the middle portion of the common bile duct; therefore the major differential diagnostic considerations were cholangiocarcinoma, cancer of the pancreas, or true biliary cysts. Congenital cysts, retention cysts, and neoplastic cysts cannot be differentiated from other true cysts preoperatively. Diagnosis can only be established by microscopic examination after surgical excision.

Adult↗

The structural gene for cytochrome c551 from Pseudomonas aeruginosa. The nucleotide sequence shows a location downstream of the nitrite reductase gene.

The gene coding for Pseudomonas aeruginosa cytochrome c551 has been cloned and its nucleotide sequence determined. Cytochrome c551 is expressed as a 104 amino acid pre-protein from which a signal peptide of 22 amino acids is cleaved off during the translocation across the cytoplasmic membrane. The gene is located just downstream of the gene coding for nitrite reductase on the Pseudomonas aeruginosa chromosome, suggesting that these genes form an operon.

Amino Acid Sequence↗

Antigens similar to major histocompatibility complex B-G are expressed in the intestinal epithelium in the chicken.

A monoclonal antibody directed against the erythrocytic B-G antigens of the major histocompatibility complex (MHC) of the chicken, an antiserum raised against purified erythrocytic B-G protein, and a cDNA probe from the B-G subregion were used to look for evidence of the expression of B-G genes in tissues other than blood. Evidence has been found in northern hybridizations, in immunoblots, and in immunolabeled cryosections for the presence of B-G-like antigens in the duodenal and caecal epithelia. Additional B-G-like molecules may be expressed in the liver as well. The B-G-like molecules in these tissues appear larger and somewhat more heterogeneous than the B-G antigens expressed on erythrocytes. Further characterization of these newly recognized B-G-like molecules may help to define a function for the enigmatic B-G antigens of the MHC. al. 1977; Miller et al. 1982, 1984; Salomonsen et al. 1987; Kline et al. 1988), and in the multiplicity of B-G restriction fragment patterns found in genomic DNA from different haplotypes (Goto et al. 1988; Miller et al. 1988; Chaussé et al. 1989). The B-G antigens have contributed, together with the B-F (class I) and B-L (class II) antigens, to the definition of over 27 B system haplotypes in experimental flocks (Briles et al. 1982). Yet the function of the B-G antigens remains entirely unknown. No mammalian counterparts have been identified, although the possibility remains that there may be similar antigens among the blood group systems of mammals. In an effort to define a function of the B-G antigens, a recently cloned B-G sequence (Miller et al. 1988; Goto et al. 1988) and antibodies to the B-G polypeptides (Miller et al. 1982, 1984) were used to examine other tissues for evidence of B-G expression.

Animals↗

The treatment of spastic planovalgus foot deformity in the neurologically impaired adult.

The surgical correction of 14 feet with spastic planovalgus in the neurologically impaired adult is reviewed. Evaluation of the patterns of lower extremity muscle activity preoperatively by dynamic EMG showed overactivity of the peroneus longus. A new gait pattern which has not been previously reported was observed. This "combination foot" deformity, noted in six patients, consists of equinovarus in swing, and planovalgus in stance during the gait cycle. The remaining eight patients exhibited planovalgus in swing and stance. Transfer of the peroneus longus tendon to either the cuboid or navicular was performed in seven (50%) patients. Release of the peroneus longus was performed in four (29%) patients. Two patients had Z-lengthening of the peroneus longus, and tenodesis of the peroneus longus to posterior tibialis was performed in one patient. The mean postoperative follow-up time was 34.6 months. All feet were plantigrade. Ten (71%) feet were balanced. Four (29%) feet were improved. There were no failures or complications. Thirteen patients were able to ambulate independently after surgery and one patient continued to require only stand-by-assistance secondary to balance problems. No patient decreased in ambulation level. Seven (64%) of the 11 patients who required bracing, preoperatively became brace free. Peroneus longus was found to be the major deforming force in spastic planovalgus. Release, transfer, or tenodesis of the peroneus longus is effective in correcting planovalgus.

Adult↗