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Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 217 records · Page 12Linked to original sources

Immunogold localisation of ubiquitin-protein conjugates in primary (azurophilic) granules of polymorphonuclear neutrophils.

Ubiquitin-protein conjugates are found in the primary (azurophilic) lysosome-related granules but not in the secondary (specific) granules in mature polymorphonuclear neutrophils prepared from bone marrow. This is the first reported demonstration of ubiquitin-protein conjugates in lysosome-related membrane-bound vesicles in granulocytes and complements our previous findings of ubiquitinated proteins in lysosomes of fibroblasts. The significance of the selective presence of conjugates in only one of the two main types of neutrophil granules remains to be elucidated but may relate to the presence of the complement of acid hydrolases, including proteases, in the azurophilic granules compared to the specific granules. Ubiquitin-protein conjugates may enter the primary granules during neutrophil maturation by an autophagic process or by a heterophagic process during the fusion of phagosomes with primary granules. Alternatively protein ubiquitination may be involved in granule biogenesis.

Animals↗

A more physiological alternative to total fundoplication for the surgical correction of resistant gastro-oesophageal reflux.

The incidence of mechanical complications associated with the Nissen fundoplication has prompted evaluation of an anti-reflux procedure designed to be simpler and more physiological, and encompassing a broader view of the many factors involved in the anti-reflux mechanism. Preliminary assessment of the first 100 patients with a mean follow-up of 3.5 years showed symptomatic improvement in 96 per cent and complete relief in 85 per cent. A further 100 patients were studied using formal symptom scoring, endoscopy, manometry and pH monitoring performed before operation and 3 months after operation. Similar clinical results were accompanied by improvement in endoscopic oesophagitis in 95 per cent, complete healing in 74 per cent and restoration of the pH profile to physiological levels in 84 per cent. Troublesome mechanical complications comprised a 2 per cent incidence of dysphagia, but there was no gas bloat or inability to belch or vomit, which may relate to the restoration of lower oesophageal sphincter characteristics close to those of 30 asymptomatic controls. The procedure is simpler to perform than total fundoplication, is well tolerated and is applicable to patients with reflux stricture and impaired oesophageal body motility. The results of this study support the hypotheses that effective reflux control can be achieved without total fundoplication by attention to several factors of known relevance to the anti-reflux mechanism, and that restoration of characteristics of the lower oesophageal sphincter close to physiological levels results in a lower incidence of mechanical complications.

Adult↗

Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus.

A recombinant vaccinia virus in which the transcription of the human immunodeficiency virus type 1 (BRU isolate) env gene is driven by the 11K late vaccinia promoter yields about 10-fold higher amounts of gp160 env protein upon infection of monkey cells than does a recombinant in which gp160 is expressed using the 7.5K early-late promoter. The gp160 was purified from detergent lysates of infected cells by lentil lectin affinity chromatography followed by immunoaffinity chromatography, and was obtained in yields of 1-2 mg/10(9) cells of material estimated to be about 70% pure. Pairs of rabbits were immunized with purified gp160 using either one of five different adjuvants or an immunostimulating complex. In all cases a substantial humoral immune response was obtained after boosting, including an activity that neutralized the homologous (BRU) isolate of HIV-1. In some cases, this activity also neutralized two distantly related isolates, SF2 and MN.

Animals↗

A double-masked evaluation of lignocaine-prilocaine cream (EMLA) used to alleviate the pain of retrobulbar injection.

A randomised, placebo controlled, double-masked study was undertaken in 115 patients undergoing cataract surgery to assess the efficacy of the anaesthetic cream EMLA (eutetic mixture of local anaesthetic, lignocaine-prilocaine) in alleviating the pain of retrobulbar injection. Sixty three patients received the EMLA cream and 52 the placebo cream. The pain was assessed objectively by the anaesthetist, who observed the reaction of the patient on needle insertion, and subjectively by the patient. Significantly lower pain scores were recorded in patients treated with EMLA cream (anaesthetist's observation: p less than 0.01, patient's assessment: p less than 0.006). No patients experienced serious side effects in either treatment group.

Aged↗

Pernicious anaemia in the textile industry.

The objective was to examine whether the observed excess mortality from anaemia in textile and clothing workers was associated with any specific anaemia type or occupational activity. The design was a death certificate based case-control study of textile and clothing workers who died in England and Wales in the years surrounding the decennial censuses of 1961, 1971, and 1981. The main outcome measures were type of anaemia, place of residence, place of birth, and occupation. The frequency of the different types of anaemia in textile and clothing workers differed from that of England and Wales with relatively more deaths from pernicious anaemia than in the country as a whole (74 observed v 55 expected deaths). Within the industry, those whose death was attributed to pernicious anaemia were more than twice as likely as other textile and clothing workers to have worked in textile mills (odds ratio = 2.4, 95% confidence interval 1.4-4.2). These results could not be explained by age, sex, place of residence, or place of birth, and review of the death certificates did not suggest that pernicious anaemia as a cause of death had been recorded in error. Historical support for the finding was found in the Registrar General's 1931 decennial supplement on occupational mortality, in which the standardised mortality ratio from pernicious anaemia in male textile mill workers was estimated to be twice that of the general population. In conclusion, occupational factors, specifically work in textile mills, could be implicated in the pathogenesis of pernicious anaemia. The aetiology of this disease is not well understood and further study of pernicious anaemia in textile mill workers is required.

Adolescent↗

Maximum airflow through the nose in humans.

Inspiratory and expiratory flow via the nose and via the mouth during maximum-effort vital capacity (VC) maneuvers have been compared in 10 healthy subjects. Under baseline conditions maximum flow via the nose was lower than that via the mouth in the upper 50-60% of the VC on expiration and throughout the VC on inspiration. The mean ratio of maximum inspiratory to maximum expiratory flow at mid-VC was 1.38 during mouth breathing and 0.62 during nasal breathing. Inspiratory flow limitation with no increase in flow through the nose as driving pressure was increased above a critical value (usually between 12 and 30 cmH2O) was found in all six subjects studied. Stenting the alae nasi in seven subjects increased peak flow via the nose from a mean of 3.49 to 4.32 l/s on inspiration and from 4.83 to 5.61 l/s on expiration. Topical application of an alpha-adrenergic agonist in seven subjects increased mean peak nasal flow on inspiration from 3.25 to 3.89 l/s and on expiration from 5.03 to 7.09 l/s. Further increases in peak flow occurred with subsequent alan stenting. With the combination of stenting and topical mucosal vasoconstriction, nasal peak flow on expiration reached 81% and, on inspiration, 79% of corresponding peak flows via the mouth. The results demonstrate that narrowing of the alar vestibule and the state of the mucosal vasculature both influence maximum flow through the nose; under optimal conditions, nasal flow capacity is close to that via the mouth.

Adult↗

Hepatobiliary imaging.

Recent publications continue to refine the technique and interpretation of hepatobiliary scanning. Studies related to the evaluation of suspected acute cholecystitis have shown that morphine-augmented hepatobiliary imaging may not overcome the problem of false-positive study results in severely ill patients and the criterion for a normal study should be gallbladder visualization within 30 rather than 60 minutes. In patients with suspected acute cholecystitis, nonvisualized extrahepatic activity despite good hepatic uptake is highly predictive of acute cholecystitis, usually with biliary obstruction. The limitations of cholecystokinin-hepatobiliary imaging studies in patients with abdominal pain syndromes were defined and its use in evaluating common bile duct dynamics, and duodenogastric reflux was explored. Unusual findings and less-common uses of hepatobiliary scanning were reported, including assessment of conjoined twins, liver transplantation, primary biliary cirrhosis, gallbladder perforation, and persistent splenic visualization.

Biliary Tract↗

Major histocompatibility complex markers and red cell antibodies to the Rh (D) antigen. Absence of association.

Between 20 and 35 percent of Rh(D) antigen-negative individuals do not develop antibodies to D even after multiple transfusions of Rh-positive red cells. To evaluate the possibility that antibody production after exposure to the D antigen was related to a major histocompatibility complex immune response gene, analysis of the HLA genotypes of 38 Rh-sensitized women and their families was performed. No significant deviations were found in the frequency of any individual HLA class I, II, or III allele or of any extended haplotype (fixed allelic combinations of HLA-B, HLA-DR, and the complement components BF, C2, C4A, and C4B). Type 1 errors due to the extreme allelic polymorphism of the HLA system, as well as the ethnic variation in patient groups, may have contributed to HLA allele-antibody responder relationships reported in earlier studies.

Female↗

Genetics of survival in mice: subregions of the major histocompatibility complex.

In this study of murine survival, 422 F1 hybrids between DBA/2J (D2) female mice and C57BL/10 (B10) background H-2 congenic male mice (11 strains), 88 F1 hybrids between B10 female mice and B10 background H-2 congenic male mice (3 strains), and 532 control mice from the 11 parental B10 background H-2 congenic mice were bred over a period of 2 yr. Toward the end of the breeding period there was documentation of Sendai infection in the mouse rooms. All analyses were done separately for the two sexes. Although it did not appear that an unusually high number of mice died during the time the colony was infected with Sendai, there was a highly significant tendency for mice who were younger at the time of the Sendai infection to have shorter survival than mice who were older at that time point. The effect of birth date on survival was approximately as significant as the effect of strain on survival. Hence all analyses of genetic effects on survival were either done within subsets of mice born in the same quarter of a particular year or else included date of birth variables in survival models. Of the 18 possible comparisons of pairs of strains which overlapped in birth dates and differed only in the D end of H-2, five were associated with highly significant survival differences. Of the 11 pairs of strains which overlapped in birth date and differed only in the K end of H-2, none was associated with significant survival differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

New drug treatment for diarrhoea.

This paper reviews the scientific background to the development of new drugs for the treatment of diarrhoeal diseases, and it includes an update of three classes of drugs which may prove useful; gut specific alpha2-adrenergic agonists, intestinal Cl- channel blockers, and somatostatin analogues.

Animals↗

Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability.

Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double-blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy.

Double-Blind Method↗