Biomedical subjects
Publications and source records attributed to J Dennis.
"X Lite", a thermoplastic material was used in eight patients as a splint for protecting split skin grafts on the back. After an average stay of 4.3 days patients were discharged with no incidence of graft failure. The patients involved felt comfortable whilst remaining supine. We believe time saved by adequate protection leading to successful grafts makes this method economically useful.
Molluscum contagiosum virus (MCV) is an unclassified poxvirus which has recently become recognized as causing a major sexually transmitted disease. At present no assay is available for specific detection of MCV because the virus cannot be serially propagated in cell culture. Since MCV produces an abortive, limited growth with some cytopathic effect in certain cell lines, we were able to develop an in situ hybridization assay for detection of MCV genome in clinical specimens. Human fetal diploid lung cell monolayers were infected with clinical specimens, and after proper incubation and fixation in paraformaldehyde, hybridization was performed under full stringency conditions with a molecularly cloned biotinylated probe. Only MCV infected cells showed homology to the MCV probe with a purple-brown cytoplasmic staining. Additionally, we have described an in situ hybridization assay for direct detection of MCV genome in formalin-fixed, paraffin-embedded biopsies. Characteristic intracytoplasmic Molluscum bodies (Henderson-Paterson bodies) were detected in stratum spinosum cells of the epidermis. Striking staining similarities have been observed between in situ hybridization and haematoxylin-eosin cytostaining. These procedures are the first successful identification of MCV genome in clinical samples by molecular hybridization, with sensitivity and specificity equal to or greater than electron microscopy.
Periconceptional supplementation with Pregnavite Forte F was offered to women who presented consecutively to the Oxford genetic counselling service in the early 1980s who had previously had one or more pregnancies complicated by a neural tube defect. The first 100 children born alive to these women are the subject of this study. Birth weight, gestation, and congenital abnormalities were recorded. At age 2-5 years all 96 children remaining in the United Kingdom were assessed clinically and developmentally and behavioural information was obtained by questionnaire. At age 7-10 years, follow up of 91 children by telephone and postal questionnaire yielded further information about growth, general health, vision, hearing, and educational and behavioural status. Entry criteria excluded single mothers but the social class distribution of the sample was otherwise representative of the Oxfordshire population. There were no recurrences of neural tube defects. One child had radiological evidence of spina bifida occulta affecting only the fifth lumbar vertebra. One had an autosomal recessive disorder. Eight had random minor congenital anomalies. Birth weight for gestational age was significantly greater than for the local population and at age 7-10 years the girls were considerably taller than expected. Health, auditory, visual, and developmental status were no different from the general population. None of the children had special educational needs. None showed a major behaviour disorder but worries, fussiness, and fearfulness were highly significantly over represented.
Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over-expressed in a simultaneous or co-ordinated fashion, thereby significantly increasing cellular invasive potential of the cells. To explore this relationship, we have measured steady-state levels of mRNA coding for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), transin and tissue-specific inhibitor of metalloproteinases (TIMP); as well as gelatinolytic, caseinolytic and plasminogen activator activities secreted by SPI, a non-metastatic mouse mammary carcinoma cell line and 4 metastatic sublines derived from it. mRNA encoding metalloproteinase transin was increased 15- to 20-fold, while TIMP transcripts were decreased 3-fold in the metastatic sublines compared to parental SPI tumor cells. Metastatic sublines secreted higher levels of gelatinase (i.e., 92 kDa and 64 kDa) as well as proteases with caseinolytic activity (i.e., 115 kDa and 57 kDa) when compared with SPI cells. Moreover, these enzymes were identified as neutral metalloproteinases. Although the amount of uPA mRNA appeared to be the same in SPI and the metastatic sublines, the latter secreted 1.5-3 times more uPA activity into the culture supernatants. Metastatic competence in the SPI tumor model is therefore associated with increased secretion of several metalloproteinase activities and uPA, as well as decreased TIMP expression, consistent with a more invasive phenotype.
The prevalence of sleep related upper airway obstruction (UAO) was studied in a cohort of 34 children with Down's syndrome from a geographically defined area. Thirty two (94%) of the children, ranging in age between 0.1 and 4.9 years (median 1.4), underwent full clinical assessment for UAO including parental questionnaires and overnight tape recordings of chest wall movements and arterial oxygen saturation (SaO2). Compared with controls, children with Down's syndrome had (a) an increased incidence of stridor and chest wall recession during sleep, (b) an increased frequency of a pattern on inspiration indicating increased upper airway resistance, (c) a reduced baseline oxygen saturation (having excluded recordings on four children with potential for right to left intracardiac shunting), and (d) an increased number of episodes with SaO2 less than or equal to 90% despite continued chest wall movements. At their initial assessment seven children (22%) had evidence of UAO. The 18 youngest children (less than or equal to 1.7 years) underwent repeated recordings and clinical assessment until they had all reached 2 years of age. A further three were found to have developed UAO. Sleep related UAO is a common problem in children with Down's syndrome, occurring in 10 of 32 (31%) of this population based sample.
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Thirteen of the 14 Down's syndrome children in Oxfordshire aged 2-4 years were studied. Quantified attention deficit was recorded for four children in a standardized test situation. This deficit did not correlate with mental age or with social or medical attributes. Temperamental traits did not identify the attention disordered children as 'difficult'. Parental ratings of behaviour revealed a preponderance of conduct-type disorder and problems of parental control among them. There was a precise inverse relationship between a child's ability to engage and maintain attention and measured examiner activity in the test situation. The implications of this for the interactive consequences of this type of attention disorder are discussed.
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Three fractions of poly(A)-containing RNA were separated from total rat liver RNA using poly(U)-Sepharose 4B affinity chromatography. The poly(A)-containing RNA fractions were released by thermal elution. Fraction 1, eluted under the mildest conditions, and had poly(A) tracts of approx. 200 AMP units in length which appeared to be associated with poly(U) sequences of 20-50 UMP in length. Fraction 1 appeared to be present mainly in the nucleus and, its size distribution was similar to that of fractions 2 and 3. Fractions 2 and 3 eluted at higher temperatures and were associated mainly with polysomal and microsomal fractions. Poly(U) sequences were absent in fractions 2 and 3 while their poly(A) sequences had a size distribution characteristic of those reported in the mRNA of other organisms.
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To explore possible advantages which immunoperoxidase (IP) staining might have over immunofluorescence (IF) staining for identifying rubella virus isolates, direct comparative studies were done on the same coded clinical materials using the same rubella immune rabbit serum as the primary antiserum in both systems. The rubella immune rabbit serum and conjugated anti-rabbit immune globulins could be used more dilute in the IP system than in the IF system. Both IP and IF staining detected rubella antigen in all specimens which were positive by interference. IP staining also detected low levels of rubella antigen in a few additional specimens which had originally been positive for rubella virus, but which on retesting were negative by interference and IF staining. With second-cell-culture-passage material, IP and IF staining showed comparable specificity, and the few specimens which reacted nonspecifically generally did so in both systems. Cell cultures inoculated directly with urine specimens showed greater nonspecificity by IP than by IF, but this activity could be abolished by pretreatment with sodium azide and peroxide; other methods tried for inactivating endogenous peroxidase activity destroyed rubella antigen as well. The intensity of staining for positive specimens was comparable in the two systems. However, more antigen was demonstrable in both systems when BHK-21 cells were inoculated as a cell suspension and then permitted to grow into monolayers than when the same specimens were inoculated into preformed monolayers. IP staining was considered to be a highly satisfactory alternative to IF staining for identification of rubella virus isolates.
An enzyme immunossay (EIA) was adapted for detection of antibody to varicella-zoster virus, and its sensitivity and specificity were compared with those of neutralization, immune adherence hemagglutination (IAHA), and complement fixation tests. Test sera showed little nonspecific reactivity in the EIA system, and valid results could usually be obtained at serum dilutions as low as 1:8. Demonstration of the presence or absence of varicella-zoster viral antibody by EIA showed 94% correlation with results obtained in neutralization tests, but EIA titers were 2- to 16-fold higher than neutralizing antibody titers. Results by IAHA showed 87% correlation with those obtained by neutralization. No false positive IAHA results were seen, but a number of false negative IAHA results were seen at the 1:8 serum dilution, particularly in older individuals. With increasing age (>40 years), and presumably increased time from varicella infection, neutralizing antibody levels generally declined to 1:8 or 1:16, EIA levels fell to 1:128 or 1:256, and IAHA and complement fixation antibody titers were usually <1:8 or 1:8. EIA and IAHA were as reliable as the neutralization and complement fixation tests for serodiagnosis of varicella and zoster infections. All tests demonstrated heterotypic varicella-zoster antibody titer rises in selected patients with initial herpes simplex virus infections, but fewer heterotypic responses were seen by EIA than by the other methods. EIA offers a rapid, sensitive, and specific method for varicella-zoster antibody assay that is applicable to use in a clinical setting.
Various subunit antigens of varicella-zoster (V-Z) virus were examined for complement-fixing (CF) activity with sera from homotypic infections and from herpes simplex virus (HSV) infections in which a CF antibody titer rise was demonstrated with crude V-Z antigen. The subunit antigens included nucleocapsids, envelopes, a soluble antigen produced from infected culture fluids by sucrose density gradient centrifugation, a soluble antigen produced by reducing the volume of clarified infected culture fluids, a soluble antigen derived from infected cell lysates, a "viral" antigen consisting largely of enveloped particles with a few nucleocapsids, and a cell membrane-associated antigen. None was more suitable than crude V-Z antigen for serodifferentiation of V-Z virus and HSV infections. The envelope antigen, cell membrane antigen, and the soluble antigen prepared by density gradient centrifugation showed little reactivity with sera from varicella and HSV infections, but gave high antibody titers with sera from zoster infections, suggesting that a secondary V-Z virus infection is required to produce an antibody response to these subunit antigens. Patients with varicella and zoster infections and the selected patients with HSV infections all showed significant CF antibody responses to the other V-Z subunit antigens.
To our knowledge, there has been reported only one previous case of prosthetic valve endocarditis due to Neisseria meningitidis. In describing a second fatal case, we emphasize the difficulty of clinical diagnosis due to lack of characteristic high fever, murmur, skin rash, or splenomegaly. This lack of findings plus the chronic, intermittent course suggest a rare occurrence of endocarditis complicating chronic meningococcemia with an acute exacerbation, leading to rapid decompensation and death.