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Biomedical subjects

J Bruce

Publications and source records attributed to J Bruce.

At least 19 recordsLinked to original sources
PubMed1995

Deletion of 3'-untranslated region alters the level of mRNA expression of a neurofilament light subunit transgene.

High levels of neurofilament (NF) mRNA expression are attained during early postnatal development and are a major determinant of axonal size. High level NF expression is also dependent upon axonal continuity since NF mRNA levels are down-regulated after nerve transection. This study shows that both postnatal up-regulation and axotomy-induced down-regulation are altered by deletion of 3'-UTR from the mouse light NF subunit (NF-L). Transgenes with (NF-L+) or without (NF-L-) 3'-UTR display similar patterns of neuron-specific expression but differ in their respective levels of expression. Whereas changes in the level of NF-L+ mRNA parallel those of the endogenous mouse NF-L mRNA, changes in the level of NF-L- mRNA differ from the pattern of endogenous NF-L expression during postnatal up-regulation and axotomy-induced down-regulation. Specifically, the NF-L- transgene undergoes a 3-fold aberrant up-regulation between embryonic days 15 (E15) and 18 (E18) and has lost its susceptibility to axotomy-induced down-regulation. Studies of transfected P19 cells show that 3'-UTR deletion leads to a severalfold stabilization of NF-L mRNA and an increase in steady-state mRNA level. The findings support the working hypothesis that the 3'-UTR contains determinants that alter stability and that stabilization of NF-L mRNA regulates the levels of NF-L mRNA in neuronal tissues and cells.

Aging↗
PubMed1995

Expression and immune recognition of stress proteins in sarcoidosis and other chronic interstitial lung diseases.

Stress proteins (SP) are major immunogens in a number of microbial infections and have been implicated in some autoimmune diseases. The aetiology of sarcoidosis, a non-caseating granulomatous disease, remains unknown, but mycobacteria as well as autoimmunity have been considered. In the present study, patients diagnosed with sarcoidosis and other interstitial lung diseases (ILD), as well as healthy volunteers were studied to determine: (i) the level of expression of SP in alveolar macrophages and blood monocytes; (ii) the serum levels of antibodies specific for mycobacterial SP65 and SP70; and (iii) the reactivity of peripheral blood and alveolar lymphocytes to mycobacterial SP65. Our results suggest that SP are expressed constitutively at high levels in alveolar macrophages, retrieved by bronchoalveolar lavage, from all individuals regardless of health status. In contrast, freshly isolated blood monocytes express low levels of SP, which are, however, readily upregulated following exposure to IFN-gamma and TNF-alpha. Lymphocyte reactivity and presence of antibodies against mycobacterial SP may reflect the current state of in vivo inflammation rather than the cause of inflammation.

Antibodies, Monoclonal↗
PubMed1995

Multicystic renal dysplasia diagnosed in the antenatal period: a note of caution.

OBJECTIVE: To document the urological problems associated with multicystic renal dysplasia (MCRD), to assess the efficacy of radiological methods for following the natural history of MCRD and to review current experience in the light of historical data regarding this condition. PATIENTS AND METHODS: From January 1982 to December 1992 data were obtained prospectively on 62 patients (41 boys and 21 girls, age range 1-11 years) who had a diagnosis of MCRD suspected on antenatal ultrasonography. All patients had the diagnosis confirmed with radioisotope scans and micturating cystograms. Serum creatinine was measured in each patient and repeated clinically as indicated. Follow-up was from 1 to 11 years, with a clinical review and an annual ultrasonogram. The natural history of these patients was compared with those in other published studies. RESULTS: Of the 62 patients, 12 had associated vesicoureteric reflux. Four patients developed impaired renal function during the course of observation and 10 patients required urological surgery for other pathologies. In the patients managed conservatively, 38% underwent no resolution on sequential ultrasonograms during the 2-year follow-up, and in four children, where complete resolution of the MCRD had occurred on ultrasonography, significant cellular renal masses were excised at subsequent surgery. CONCLUSION: Patients with MCRD have significant associated urological malformations and the natural history in such patients is unpredictable. We do not regard MCRD as an entirely benign condition and feel that all patients require appropriate investigation of their urinary tract and long-term follow-up where conservative treatment is instituted. From the natural history of these patients, reviewed in conjunction with the literature, we recommend that decisions for management can only be taken with the full informed consent of the parents and that surgical excision is offered as part of that process.

Child↗
PubMed1995

Ileocystoplasty in children: assessing safety and success.

From 1987 to 1992, bladder augmentation using clam ileocystoplasty was performed in 39 children 1.5-17.5 years old (mean age 9.7 years). Indications for augmentation included neuropathic bladder, epispadias-exstrophy complex and posterior urethral valves. A satisfactory bladder capacity at safe storage pressures of < 20 cm saline was achieved in all patients. Hydroureteronephrosis resolved or improved in 33 of the 36 moieties (91.7%). No patient showed biochemical or radiological deterioration of the upper tracts. The incidence of symptomatic urinary tract infection fell significantly postoperatively. Seven patients (17.9%) developed a total of 10 complications, with rupture of the augmented bladder occurring in 4 patients (10.3%).

Adolescent↗
PubMed1995

MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme.

The multiple tumor suppressor 1 (MTS1) gene encoding the p16 inhibitor of cyclin-dependent kinase 4 is deleted or mutated in a wide variety of human tumor cell lines, but the importance of this gene as a tumor suppressor in vivo appears to be highly dependent on tumor type. Because MTS1/p16/CDKN2 and the homologous MTS2/p15 gene map to a region of chromosome 9p21, which is frequently deleted in malignant gliomas, we searched for lesions of these genes in primary biopsies of glioblastoma multiforme (GBM). Our analysis confirms a sizable frequency of homozygous deletion of MTS1/p16/CDKN2 (9/27 cases) and also reveals a low but detectable frequency of intragenic DNA lesions (one point mutation in exon 2 leading to premature termination) among GBMs that retain one or both copies of the gene. No mutations were found in exon 2 of MTS2/p15 (12 cases examined), and one GBM showed a DNA deletion breakpoint in the 30 kb between MTS1/p16/CDKN2 and MTS2/p15 resulting in deletion of MTS1/p16/CDKN2 with retention of MTS2/p15. In contrast to the high-grade tumors, none of 12 low-grade gliomas showed MTS1/p16/CDKN2 deletions. These data support a role for MTS1/p16/CDKN2 as a tumor suppressor gene in the in vivo evolution of GBMs. Given that two tumors with hemizygous MTS1/p16/CDKN2 deletions and loss of heterozygosity for chromosome 9p21 did not contain detectable intragenic mutations, there may be one or more additional relevant 9p21 tumor suppressor genes.

Base Sequence↗
PubMed1994

Brain-specific enhancement of the mouse neurofilament heavy gene promoter in vitro.

We have investigated the DNA elements responsible for transcription from the proximal portion of the mouse neurofilament heavy gene (NF-H) promoter by in vitro transcription using extracts from expressing (brain) and non-expressing (liver) tissues. We have found that constructs containing 5' region from -1314 to -115 exhibit a 3-5-fold higher level of NF-H promoter activity, relative to the adenovirus major late promoter (pML), in brain versus liver extracts. Deletion to -85 lowers the level of brain transcription by 2-fold, while deletion from -65 through -31 reduces transcription by 5-fold to a relatively strong (10% of pML) basal level. Basal level expression is observed in all deletions transcribed with liver extract. Deletion to -24 (TATA-less) abolishes promoter activity with both extracts. Deletion of the -115 to -65 region from a larger construct reduces transcription in brain extracts to basal levels, suggesting that this region contains the elements necessary for the brain-specific enhancement of promoter function. Mutation of a palindromic sequence within this region abolishes brain-specific enhanced promoter activity. This loss of enhanced transcriptional activity is correlated with the loss of a shifted band in gel shift assays. Our studies suggest that the sequence (-106)GGGGAGGAGG-(15 bp)-CCTCCTCCCC(-72) (where bp = base pairs) is important in brain-specific enhancement of transcription from the mouse NF-H promoter.

Adenoviridae↗
PubMed1994

Zoonotic transmission of giardiasis: a case control study.

A case control study of locally acquired giardiasis was carried out in a district in East Anglia. Thirty-three primary cases were matched for age and sex with 112 controls selected from Family Health Service Authority registers. An association was shown between giardiasis and contact with farm animals (odds ratio 4.77; confidence interval 1.31-17.38) and pets (odds ratio 14.55; confidence interval 4.18-50.62).

Adolescent↗
PubMed1994

Meningiomas of the cranial base.

Treatment objectives for meningiomas of the cranial base include relief of neurologic disability and prevention of clinical progression or recurrence with the least morbidity. Recent advances in skull base surgical techniques, through an appreciation of skull base anatomy and institutional specialization, have contributed major improvements to the outlook for patients with these tumors, and previously inoperable cases may now often be removed completely with acceptable risk. Since significant morbidity may be incurred during surgical resection of these difficult lesions, especially in terms of cranial nerve dysfunction, the value of aggressive surgical resection must be weighted against the often indolent natural history of these lesions, and must be individualized in each patient. Completeness of resection is the major prognostic factor determining the outcome of patients with typical benign meningiomas in terms of length of survival, risk of recurrence, and neurological disability. Various means of prognosticating the growth potential of a given tumor are being investigated, though none have yet been confirmed for their predictive value in typical, histologically benign meningiomas. The role of external beam radiotherapy has not been subjected to adequately controlled, prospective studies, and there is currently insufficient followup to assess the risks and benefits of stereotactic radiosurgery. Advances in the clinical management of tumors of the skull base has had perhaps the greatest impact for patients with meningiomas who constitute a large portion of tumors seen in these locations. Although the majority have benign histological features, skull base meningiomas can present a formidable challenge due to their proximity to vital structures, surgical inaccessibility, and occasional aggressive features. The combination in recent years of advances in skull base surgical techniques, adjuvant therapy, and rehabilitation methods have dramatically improved the outcome for these tumors.

Adolescent↗
PubMed1994

Stabilization of neurofilament transcripts during postnatal development.

Neurofilament (NF) mRNAs in primary sensory neurons are long-lived transcripts that undergo transcription-dependent destabilization when placed in primary culture [32]. Destabilization of NF transcripts implies that the transcripts are stabilized in high-expressing neurons and that stabilization may coordinate and increase levels of NF expression. The present study examines the stabilities of the three NF subunit mRNAs in postnatal cultures of dorsal root ganglia (DRG) to determine whether increased stability of NF mRNAs could be responsible for the coordinate postnatal upregulation of the three NF subunits [29]. The studies show that the light (NF-L), mid-sized (NF-M) and heavy (NF-H) NF mRNAs are lost at 8 and 16 h in primary cultures from postnatal day 2 (P2) rats, but much less so in cultures from postnatal day 16 (P16) and day 30 (P30) rats. Losses of each NF mRNAs in P2 cultures occurs simultaneously in the presence or absence of actinomycin. The findings support the view that stabilization of NF transcripts contribute to the high and coordinate level NF expression and that components of the stabilizing process are acquired during postnatal development.

Actins↗
PubMed1994

Polydipsia amongst adults with a learning disability in an institution.

A hospital-based adult learning disabled population (n = 371) was screened for polydipsia with the help of a purpose-designed questionnaire. Polydipsia was defined as excessive drinking of more than 3 l of non-alcoholic fluid over a 24-h period. Altogether, 23 (6.2%) subjects were found to have polydipsia. The polydipsic group was compared with the whole hospital population on variables such as age and IQ distribution. A matched group of 23 individuals without a history of polydipsia was drawn from the same hospital population. The polydipsic and the matched group were compared using various biochemical and psychological measures. Thirty-five per cent of polydipsic patients, compared to 13% of the matched group, showed evidence of compensated hyponatraemia. This difference was not significant. There was no significant difference between the polydipsic and the matched group in the frequency of psychiatric illness, behavioural problems or autism. There also was no significant difference in the IQ levels of the polydipsic patients and the total hospital population. Polydipsia in this population is largely seen as part of an abnormal behavioural repertoire without any evidence of possible organic cause, except unidentified diabetes mellitus. Klein Levin syndrome and pica were represented in the polydipsic group, but not amongst the matched group.

Adult↗
PubMed1994

Piccadilly Circus legionnaires' disease outbreak.

BACKGROUND: An outbreak of legionnaires' disease occurred in central London in January and February 1989. An Infection Control Committee was established to investigate the outbreak and institute control measures. The objective of this paper is to describe the investigation and control of the outbreak. METHODS: An epidemiological survey and case-control study were carried out. The subjects were cases of community acquired pneumonia associated with central London with onset of illness in January and February 1989. RESULTS: Thirty-three confirmed cases, including five deaths, and ten suspected cases, including three deaths, were identified with dates of onset from 1 January to 11 February. A clustering of visits by cases to the vicinity of Piccadilly Circus was noted, and a case-control study demonstrated a strong association between illness and visits to this area in the two weeks before onset of symptoms. The causative organism, Legionella pneumophila serogroup 1, was isolated from six patients. Legionella pneumophila of the same serogroup was isolated from water samples from five wet cooling systems (cooling towers) in the area under investigation, but in only two systems was the organism indistinguishable by subtyping from the patients' strains. Many of the cooling towers examined were inadequately maintained, including one of the two above a building adjacent to Piccadilly Circus from which a strain indistinguishable from the outbreak strain was isolated. All cooling towers in the area were shut down until inspected, and only allowed to restart after appropriate maintenance had been instigated. CONCLUSIONS: This outbreak showed the continuing risk of legionnaires' disease posed by wet cooling systems, including cooling towers, and highlighted the need to assess this risk so that appropriate maintenance is carried out. Regulations have recently been introduced, under the Health and Safety at Work Act, requiring notification of all wet cooling systems to the local authority to facilitate the investigation of outbreaks of legionnaires' disease.

Adolescent↗
PubMed1994

Assessment of praziquantel therapy in treatment of Schistosoma mansoni infection.

The present study is the first report of the epidemiological survey carried out as a part of the Praziquantel resistance project which is one of the projects of Schistosomiasis Research Project (SRP) in Egypt. The results of the study, which has been carried out in 3 villages, revealed that praziquantel is effective as an antischistosomal drugs and reduced egg count significantly. However at the end of the study some cases remained infected in spite of the three treatment regimens. Several factors can be responsible, among them is the presence of resistance strains, which will only be elucidated in the subsequent steps of the project, when identification of resistant strains in experimental animals will be carried out.

Drug Resistance↗