Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 325 records · Page 18Linked to original sources

PubMed1996

The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism.

Eukaryotic rRNAs (with the exception of 5S rRNA) are synthesized from a contiguous pre-rRNA precursor by a complex series of processing reactions. Final maturation of yeast 5.8S rRNA involves processing of a 3'-extended, 7S precursor that contains approximately 140 nucleotides of the internal transcribed spacer 2 (ITS2) region. In yeast strains carrying the temperature-sensitive (ts) rrp4-1 mutation, 5.8S rRNA species were observed with 3' extensions of variable length extending up to the 3' end of the 7S pre-rRNA. These 3'-extended 5.8S rRNA species were observed at low levels in rrp4-1 strains under conditions permissive for growth and increased in abundance upon transfer to the nonpermissive temperature. The RRP4 gene was cloned by complementation of the ts growth phenotype of rrp4-1 strains. RRP4 encodes an essential protein of 39-kD predicted molecular mass. Immunoprecipitated Rrp4p exhibited a 3'-->5' exoribonuclease activity in vitro that required RNA with a 3'-terminal hydroxyl group and released nucleoside 5' monophosphates. We conclude that the 7S pre-rRNA is processed to 5.8S rRNA by a 3'-->5' exonuclease activity involving Rrp4p. Homologs of Rrp4p are found in both humans and fission yeast Schizosaccharomyces pombe (43% and 52% identity, respectively), suggesting that the mechanism of 5.8S rRNA 3' end formation has been conserved throughout eukaryotes.

Amino Acid Sequence↗

PubMed1996

Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study.

OBJECTIVE: To determine the prevalence and associations of retinal vein occlusion (RVO) in a defined older Australian population. DESIGN: Participants (N = 3654; age, > or = 49 years), representing 88% of the permanent residents from an area west of Sydney, Australia, underwent a detailed eye examination, including stereophotography (Zeiss). The diagnosis of RVO was made clinically and from photographic grading. RESULTS: Signs of RVO were found in 59 participants (1.6%; 95% confidence interval, 1.3-1.9). The prevalence for each age-specific participant was as follows: 0.7%, younger than 60 years; 1.2%, 60 to 69 years; 2.1%, 70 to 79 years; and 4.6%, 80 years or older. There was no significant sex difference in prevalence. Branch RVO was observed in 41 subjects (69.5%); of this number, 10 subjects had branch RVO outside the vascular arcade or in the nasal fundus and 3 subjects developed new vessels. Hemispheric RVO was found in 3 subjects (5.1%), and central RVO was observed in 15 (25%); RVO was bilateral in 3 subjects (5.1%). Visual acuity was affected most in the people with central RVO, with a visual acuity of 20/200 or less in 60% compared with 14% among the people with branch RVO. Retinal vein occlusion was the fifth most frequent cause of unilateral blindness in this population. Significant associations with RVO were found with glaucoma, hypertension, stroke, and angina. CONCLUSIONS: This study emphasizes RVO as an important cause of unilateral visual loss in an older population. The proportion of the 3 vein occlusion sites shows some differences from those of clinic-based reports and suggests a likely selection bias in previous clinic studies.

Aged↗

PubMed1996

Smoking and age-related maculopathy. The Blue Mountains Eye Study.

OBJECTIVE: To assess the associations between stage of age-related maculopathy (ARM) and current, past, and passive smoking. METHODS: A cross-sectional study of 3654 subjects from a defined geographic area west of Sydney, Australia, identified subjects with late age-related macular degeneration (AMD) and early ARM by ocular examination and detailed grading of retinal photographs. Interviewer-administered questionnaires provided data about smoking history for subjects and spouses. Logistic regression, adjusting for age and sex, and 2-way analysis of variance were used to assess associations. RESULTS: Current tobacco smoking was significantly associated with late AMD (odds ratio [OR], 3.92), including neovascular AMD (OR, 3.20) and geographic atrophy (OR, 4.54), and early ARM (OR, 1.75). Having ever smoked was significantly associated with late AMD (OR, 1.83) but not early ARM. Passive smoking was associated with increased but insignificant odds for late AMD. The risk was slightly higher among women compared with men for most exposure categories. CONCLUSIONS: These findings provide convincing evidence that smoking may be causally associated with ARM. The strongest risk was found for current smokers, suggesting potential benefits of targeting education to older people who are current smokers and have signs of early ARM.

Aged↗

PubMed1996

Psoriatic arthritis in a fifth-century Judean Desert monastery.

Psoriatic arthritis is a greatly underreported seronegative erosive arthropathy, due to the ambiguous lesions it leaves on bone in all but the most severe cases. For a confident diagnosis of psoriatic arthritis to be made, sacroiliac and intervertebral joint fusion must be present together with erosive lesions of the peripheral skeleton including most especially the terminal interphalangeal joints. In modern times it is only a small percentage of cases who experience such debilitating disease, which may explain who so few cases of psoriatic arthritis can confidently be identified from past populations. This report describes this pathological condition as observed in the comingled skeletal remains of nine males and one female from the tomb of Paulus in the Byzantine Monastery of Martyrius, in the Judean Desert. Visual study was complemented using radiographic techniques along with scanning electron microscopy. Two adult males show characteristic lesions of psoriatic arthritis, demonstrating the form known as arthritis mutilans. A third individual shows less widespread erosive lesions which may signify a pauciarticular example of psoriatic arthritis, as is true of most cases in modern times, or the remains may represent Reiter's disease. During the Byzantine period the earlier practise of expelling those with disfiguring diseases (biblical leprosy) evolved into a philanthropic, caring philosophy where the sick were housed and fed out of charity, often within monasteries. The presence of these cases of psoriatic arthritis within such a Judean Desert monastery confirms earlier suggestions that psoriasis was one of the diseases included by those in the ancient eastern Mediterranean under the umbrella term of biblical leprosy.

Arthritis, Psoriatic↗

PubMed1996

Contamination in reasoning about false belief: an instance of realist bias in adults but not children.

Children aged around 5 and 9 years and adults were presented with stories and videos about a protagonist who heard a message purporting to provide factual information. Observing subjects knew whether the message was true or false. In some cases, this message contradicted the listener's existing belief based on what he or she had seen previously. Subjects judged whether the listener would believe or disbelieve the message. Child subjects frequently judged that a contradicting message would be disbelieved, irrespective of whether they (the child subjects) knew it to be true or false. In contrast, adult subjects made judgements that were contaminated by their own privileged knowledge of the truth. For three different scenarios, adult subjects judged more frequently that the message would be believed if they (but not the listener protagonist) knew it to be true, than if they thought it was false.

Adolescent↗

PubMed1996

Alcohol intake and age-related maculopathy.

PURPOSE: To assess associations between alcohol intake and age-related maculopathy. METHODS: A population-based study of 3,654 subjects identified cases of late age-related macular degeneration, early age-related maculopathy, and any large drusen (larger than 125 microns) by examination and grading of retinal photographs. Interviewer-administered questionnaires provided data on alcohol intake. RESULTS: Neither total alcohol intake nor intake of beer specifically was significantly associated with age-related maculopathy, although a significant positive association was found between consumption of spirits and early age-related maculopathy. CONCLUSIONS: These findings provide little evidence that alcohol is causally associated with age-related maculopathy.

Aged↗

PubMed1996

Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.

PURPOSE: The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older. SUBJECTS: There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census. METHODS: All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry. RESULTS: A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension. CONCLUSIONS: These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.

Age Distribution↗

PubMed1996

Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study.

BACKGROUND: The Blue Mountains Eye Study is a population-based study of vision and the causes of visual impairment and blindness in a well-defined urban, Australian population 49 years of age and older. METHODS: The logarithm of the minimum angle of resolution (logMAR) visual acuity was measured before and after refraction in 3647 persons, representing an 88% response rate in two postcode areas in the Blue Mountains area, west of Sydney. RESULTS: Refraction improved visual acuity by one or more lines in 45% of participants and by three or more lines in 13%. Visual impairment (visual acuity 20/40 or worse in the better eye) was found in 170 participants (4.7%). Mild visual impairment (Snellen equivalent 20/40 to 20/60 in the better eye) was found in 3.4% moderate visual impairment (20/80 to 20/160 in the better eye) in 0.6%, and severe visual impairment or blindness (20/200 or worse in the better eye) in 0.7%. Visual impairment increased with age from 0.8% of persons 49 to 54 years of age to 42% of persons 85 years of age or older. Visual impairment was significantly more frequent in females at all ages. Among persons with severe visual impairment, 79% were female. After adjusting for age, females were less likely to achieve 20/20 best-corrected visual acuity than males (odds ratio, 0.57; confidence interval, 0.48-0.66). After adjusting for age and sex, no association was found between visual acuity and socioeconomic status. Age-related macular degeneration was the cause of blindness in 21 of the 24 persons with corrected visual acuity of 20/200 or worse. CONCLUSION: Increasing age and female sex were independent predictors of visual impairment.

Adult↗

PubMed1996

Cooperative hernia study. Pain in the postrepair patient.

BACKGROUND: The Cooperative Hernia Study assessed postoperative pain in a prospective trial as part of a larger study looking at the recurrence rate and other morbidity of the Bassini, McVay, and Shouldice repairs. METHODS: Patients were randomized to one of three surgical hernia repairs. Patients were seen in follow-up at 6, 12, and 24 months and were assessed for the presence of pain, numbness, paresthesia, and recurrence. RESULTS: Three hundred fifteen patients were seen in follow-up, with 276 seen at the 2-year mark. At 1 year, 62.9% of patients had groin or inguinal pain and 11.9% of patients had moderate to severe pain; 53.6% had pain and 10.6% of patients continued to report moderate to severe pain 2 years postoperatively. The predictors for long-term postoperative pain were as follows: absence of a visible bulge before the operation (p < 0.001); presence of numbness in the surgical area postoperatively (p < 0.05); and patient requirement of more than 4 weeks out of work postoperatively (p < 0.004). Three distinct chronic pains were identified. The most common and most severe pain was somatic, localized to the common ligamentous insertion to the public tubercle. The second was neuropathic and was referable to the ilioinguinal or genitofemoral nerve distribution. This was likely because of injury to the genitofemoral nerves, either at surgery or subsequently by encroachment of scar. The third pain was visceral, ejaculatory pain. Twenty-four percent of patients had postoperative numbness at 2 years, independent of the type of repair. Numbness was most common in the distribution of cutaneous branches of the ilioinguinal and iliohypogastric nerves. CONCLUSION: Pain or numbness are common late sequelae of traditional external surgical hernia repairs. Strategies need to be developed to reduce the risk of these complications.

Adult↗

PubMed1996

Pneumothorax during laparoscopic mobilization of the oesophagus.

During laparoscopic dissection of the oesophagus, the left pleura is easily breached, resulting in pneumothorax. This complication has not been widely reported, although it is likely to be common. Management depends on subsequent cardiorespiratory effects, which are variable. Five cases are reported from an initial experience of 190 laparoscopic Nissen fundoplications, illustrating a variety of presentations and management options.

Adult↗

PubMed1996

Consequences of success: do more teeth translate into more disease and utilization?

OBJECTIVES: Increased tooth retention coupled with increased numbers of older adults means that the actual number of teeth at risk to dental disease will increase sharply. Whether this increase in the number of teeth will translate into more disease and utilization in unknown. The purpose of this study was to test this "more teeth, therefore more dental disease" theory using cross-sectional data. METHODS: In-home personal interview and oral examination data were obtained on a probability sample of elders aged 70 years and older living in the six New England states using the Medicare beneficiary list as a sampling frame. Data on dental utilization, number of teeth, dental caries, and periodontal disease were included in the current analysis. RESULTS: Analysis of variance on subjects with 1-10 (Group 1), 11-24 (Group 2), and 25-32 (Group 3) teeth show that the extent of bleeding on probing, pocket depth, and loss of attachment all increase as numbers of teeth increase. Similarly, a greater number of restored coronal and root surfaces were found in Group 3 relative to the other two groups. Mean numbers of decayed and filled coronal surfaces were 8.4 in Group 1.33.0 in Group 2, and 50.3 in Group 3. In contrast, unrestored coronal and root surface were significantly higher in Group 1 (mean root DS = 1.3) than Group 3 (mean root DS = 0.3). Utilization patterns of those with successful aging dentitions (Group 3) show that they are visiting dentists more frequently than the compromised group (Group 1). CONCLUSIONS: These cross-sectional data obtained from a probability sample of New England elders show that subjects who retained higher numbers of teeth have more periodontal disease and dental caries experience, and visit the dentist more frequently.

Aged↗

PubMed1996

Immunological detection of type II collagen degradation: use in the evaluation of anti-arthritic therapies.

Propagated Swaram rat chondrosarcoma cells, rabbit chrondrocytes (from articular cartilage of knee, shoulder and hip joints), and bovine nasal cartilage explant cultures were studied. Type II collagen (CII) and its peptide fragments were quantitated in cell medium and cell layer separately, using two previously developed assays; one assay employed a monoclonal antibody, C4F6, that reacts specifically with triple helical CII and the other assay used an antibody, EIE5, that reacts specifically with a peptide of CII. A time-dependent increase in the content of CII and CII-derived peptides was observed in both rat and rabbit cultures. In both culture systems the majority of the native type II collagen is found associated with the cell layer (97% in rat cultures and 73% in rabbit cultures), while the major part of the CII peptides is found in the media (73% in rat cultures, 88% in the rabbit cultures). The concentration of peptides in the media reaches approximately 2 micrograms mL-1 in both chondrocyte monolayer cultures after 4 days. The CII peptide assay employing E1E5 was well suited to quantitate articular cartilage collagen degradation in explant culture. thus it can be used to evaluate potential therapeutic agents that can modify or inhibit cartilage degradation. The assay has the added potential that it could be used in-vivo to evaluate the effectiveness of potential metalloproteinase inhibitors in animal models of osteoarthritis or in clinical trials.

Animals↗

PubMed1996

If the referral fits: bridging the gap between patient and referrer requirements in a tertiary referral unit.

OBJECTIVE: We examined the reasons for which doctors refer and patients request referral to our tertiary Mood Disorders Unit (MDU), focussing on congruence and 'fit', and the potential for more efficient use of referral resources. METHOD: A postal survey of patients (n = 265 or 83% responders) and referrers (n = 156 or 94% responders) sought views regarding referral and service components. Ratings from 156 matched referrer-patient dyads were compared. RESULTS: Overall, referrers and patients were satisfied with the MDU. There was disparity between what referrers sought and what patients thought were the reasons for referral, and different perceptions of the value of interventions and the amount of improvement. Congruent matched referrer-patient judgements of patient outcome were more likely to correspond with objective clinician ratings than discordant ratings. Satisfaction with MDU contact or intervention was not necessarily linked to improvement; better management of chronic depression was also valued. Referrer and patient responses to open-ended questions highlighted beneficial ingredients of referral. CONCLUSIONS: There was considerable lack of fit between referrers' and patients' experience of the referral. Better communication between referrer and patients can clarify the purpose of referral and possibly lead to increased compliance with medical regimens.

Adolescent↗

PubMed1996

Defining the personality disorders: description of an Australian database.

OBJECTIVE: We seek to improve the definition and classification of the personality disorders (PDs) and derive a large database for addressing this objective. METHOD: The paper describes the rationale for the development of a large set of descriptors of the PDs (including all DSM-IV and ICD-10 descriptors, but enriched by an additional 109 items), the design of parallel self-report (SR) and corroborative witness (CW) measures, sample recruitment (of 863 patients with a priori evidence of personality disorder or disturbance) and preliminary descriptive data. RESULTS: Analyses (particularly those comparing ratings on molar PD descriptions with putative PD dimensions) argue for acceptable reliability of the data set, while both the size of the sample and the representation of all PD dimensions of interest argue for the adequacy of the database. CONCLUSIONS: We consider in some detail current limitations to the definition and classification of the PDs, and foreshadow the analytic techniques that will be used to address the key objectives of allowing the PDs to be modelled more clearly and, ideally, measured with greater precision and validity.

Adult↗

PubMed1996

Clinical and subclinical hypothyroidism in patients with chronic and treatment-resistant depression.

OBJECTIVE: To investigate the relationship between hypothyroidism and treatment-resistant depression (TRD). METHOD: A retrospective case audit of 93 inpatients of a specialist Mood Disorders Unit. Patients referred with TRD were sub-classified into 'adequate' or 'inadequate' prior treatment groups on the basis of pre-established criteria, and compared with a 'non-TRD' control sample. Grades I (clinical) and II (subclinical) hypothyroidism were determined by review of relevant thyroid indices. RESULTS: Patients had chronic depressive disorders (sub-group means of 57.5-82.2 weeks of illness). Of those patients referred with TRD, 22% (10/46) had evidence of clinical or subclinical hypothyroidism compared with 2% (1/47) of the non-TRD patients (p < 0.01). A gradient in the rates of grade I hypothyroidism was observed with the adequately-treated TRD patients having the highest rate (13%), the inadequately-treated TRD patients having an intermediate rate (7%), and the non-TRD patients having the lowest rate (2%). Consistent with this view, the inadequately-treated TRD group had the highest rate of grade II hypothyroidism (p = 0.01) and tended to have higher thyroid stimulating hormone (TSH) values (p = 0.06). Differences in the rates of hypothyroidism could not be accounted for by differences in age or prior exposure to lithium and/or carbamazepine. Duration of the depressive episode was negatively correlated with both the free thyroxine indices (r = -0.25, P < 0.05) and TSH levels (r = -0.32, p < 0.01). CONCLUSIONS: This study suggests that relative hypothyroidism may play a role in the development of some treatment-resistant depressive disorders.

Adult↗

PubMed1995

Transcriptional activation by Myc is under negative control by the transcription factor AP-2.

The Myc protein binds to and transactivates the expression of genes via E-box elements containing a central CAC(G/A)TG sequence. The transcriptional activation function of Myc is required for its ability to induce cell cycle progression, cellular transformation and apoptosis. Here we show that transactivation by Myc is under negative control by the transcription factor AP-2. AP-2 inhibits transactivation by Myc via two distinct mechanisms. First, high affinity binding sites for AP-2 overlap Myc-response elements in two bona fide target genes of Myc, prothymosin-alpha and ornithine decarboxylase. On these sites, AP-2 competes for binding of either Myc/Max heterodimers or Max/Max homodimers. The second mechanism involves a specific interaction between C-terminal domains of AP-2 and the BR/HLH/LZ domain of Myc, but not Max or Mad. Binding of AP-2 to Myc does not preclude association of Myc with Max, but impairs DNA binding of the Myc/Max complex and inhibits transactivation by Myc even in the absence of an overlapping AP-2 binding site. Taken together, our data suggest that AP-2 acts as a negative regulator of transactivation by Myc.

Animals↗

PubMed1995

Deletions and rearrangement of CDKN2 in lymphoid malignancy.

Recurrent abnormalities of the short arm of chromosome 9, including translocations and interstitial deletions, have been reported in both leukemia and lymphoma. The pathologic consequences of these abnormalities remain unknown. The cyclin-dependent kinase 4 inhibitor (CDKN2) gene, which maps to 9p21, has been implicated by the finding of a high frequency of biallelic deletions in leukemic cell lines. We have determined the incidence of structural abnormalities affecting CDKN2 by DNA blot in a panel of 231 cases of leukemia and lymphoma and 66 cell lines derived from patients with lymphoid malignancies with defined cytogenetic abnormalities. Structural alterations of CDKN2 were seen in 20 (8.3%) of all fresh cases and 10 (15.1%) of all cell lines. Biallelic CDKN2 deletions were seen in 11 of 53 (21%) cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). There was no association with any particular cytogenetic abnormality. Biallelic deletions were also found in high-grade and transformed non-Hodgkin's lymphoma (NHL) of both B- and T-cell lineages. In two cases of transformed NHL, analysis of sequential samples showed loss of CDKN2 with transformation. Neither deletions nor rearrangements of the CDKN2 gene were seen in any of the 119 leukemias of mature B or T cells analyzed. Biallelic deletions of CDKN2 were observed in 6 of 13 NHL cell lines. Three of the 6 cases had undergone transformation from low- to high-grade disease: in 2 of these cases it was possible to show that the CDKN2 deletions were present in fresh material from the patient and were therefore not an artifact of in vitro culture. Rearrangements of CDKN2 were seen in 2 cases (4%) of BCP-ALL, in 1 case of B-NHL, and in 1 Burkitt's lymphoma cell line and suggest the presence of a "hot spot" for recombination in the vicinity of the CDKN2 gene. These data indicate that the loss of CDKN2 expression may be involved in the pathogenesis of a subset of BCP-ALL, some high-grade NHL, and in the transformation of NHL from low- to high-grade disease. CDKN2 deletions and rearrangements occurred in the absence of detectable cytogenetic changes of chromosome 9p in 25 of 30 (83%) cases. Finally, of 10 cases of BCP-ALL that produced overt, transplantable leukemia in mice with severe combined immunodeficiency (SCID), seven showed biallelic CDKN2 deletions. In contrast, none of 11 cases that failed to engraft showed biallelic CDKN2 deletions. BCP-ALL cases that lack CDKN2 expression may have a particular propensity to grow in SCID mice.

Adolescent↗

PubMed1995

Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression.

In 39 hospital inpatients with severe primary depressive disorders, we evaluated the relationships between subcortical hyperintensities on magnetic resonance imaging (MRI) and clinical features, neuropsychological impairment and response to standard therapies. Both white matter and gray nuclei lesions were associated with older age and the absence of a family history of affective disorder. White matter hyperintensities were also associated with onset of first affective episode after the age of 50 years and impaired psychomotor speed. Most importantly, the severity of white matter hyperintensities predicted a poorer response to treatment (r = -0.44, p < .01). Negative correlations of the same order were detected in those (n = 20) who received electroconvulsive therapy (r = -0.42, p = .06) and those (n = 19) who received pharmacotherapy alone (r = -.49, p < .05). This study provides preliminary evidence supporting the clinical and prognostic significance of extensive white matter hyperintensities in patients with severe depression.

Activities of Daily Living↗