Biomedical subjects
Publications and source records attributed to R Scott.
In Japan, Spain, and the USA during one week acts of violence (verbal and nonverbal) were rated on the Index of Television Violence by 3 raters in each country. In all three countries televised violence was more likely depicted in interpersonal conflict than against property. Fewer scenes of physical or fatal injury appeared in Japan than in the other two countries. Other observations were made. Replication is urged.
An immunohistochemical method for assessing the level of tumour necrosis factor-alpha in alveolar macrophages obtained by brochoalveolar lavage is described. Cytospins of mixed populations of lung cells were incubated first with a monoclonal antibody to CD68 and then with a specific peroxidase-labelled second antibody in a two-step reaction for the detection of the macrophage marker CD68. A second similarly based two-step reaction for the detection of tumour necrosis factor-alpha followed. Both reactions were visualized, on completion, using different coloured peroxidase substrates which produced a third colour in the event of dual deposition of the substrates. Dual substrate deposition was indicative of alveolar macrophages positive for tumour necrosis factor-alpha. This method has provided a specific and reproducible semi-quantitative test for the presence of tumour necrosis factor-alpha in human activated alveolar macrophages, which can be performed retrospectively on clinical material. A range of concentrations of the cytokine has been demonstrated in individual samples. This dual detection method has the potential for detection of any cell-associated protein product by minor modification of the described method.
A striking feature of Fanconi anemia (FA) cells is their hypersensitivity towards crosslinking agents such as mitomycin C (MMC). In this study, we have shown that treatment of lymphoblastoid cells with MMC resulted in nuclear fragmentation, chromatin condensation, and DNA degradation, which is characteristic of apoptosis. The level of DNA fragmentation 48 hours after MMC treatment reached approximately 33% in both control and FA cells. In addition, 24 hours after drug addition a decrease in the number of cells in the G2/M phase of the cell cycle was seen. This coincided with the appearance of apoptotic cells in the sub-G1 phase, indicating that once the cells had passed through G2/M, apoptosis occurred. The number of apoptotic cells increased to 60% 96 hours after MMC treatment. The number of apoptotic cells increased to 60% 96 hours after MMC treatment. The onset and level of apoptosis was found to be identical in FA and control cell lines, indicating that the FA defect does not lead to abnormal apoptotic cell death.
A 4.2-kDa polypeptide termed beta protein (A beta) accumulates in senile plaques and blood vessels in Alzheimer's disease and Down's syndrome. It is widely believed that A beta is the product of the posttranslational processing of a larger precursor protein, the beta amyloid precursor protein (APP). The proteolytic processes involved in the generation of the A beta are virtually unknown. Here the purification and characterization of a protease from Alzheimer's disease brain capable of cleaving a 10 amino acid synthetic substrate flanking the N terminus of A beta at the Met-Asp bond are described. Most importantly, the purified protease degrades human recombinant APP and generates a 15-kDa amyloidogenic fragment. The protease requires the presence of a reducing agent for its activity. Its pH optimum is around physiological pH, while the enzyme is inactive at acidic pH (below pH 5.0) and basic pH (over pH 7.6). The enzyme is inhibited by N-ethylmaleimide, (hydroxymercuri)benzoate, 1.10-phenanthroline, EDTA, and EGTA. Phenylmethanesulfonyl fluoride has no effect on its activity. This protease is devoid of caseinolytic or gelatinase activities, as well as activities against cathepsin B and cathepsin L substrates. Sequence analysis reveals high homology to the rat metallopeptidase EC 3.4.24.15, a protease involved in neuropeptide processing.
OBJECTIVE: To detect characteristics of persons with ocular hypertension that are associated with a higher risk of future glaucomatous field loss. METHODS: Annual examinations of the optic disc, nerve fiber layer, and visual field in 647 persons with bilateral intraocular pressure higher than 21 mmHg and initially normal visual field test results with the Goldmann perimeter. RESULTS: Sixty-eight persons developed a field defect on two consecutive Goldmann visual field tests in at least one eye, while 579 others retained normal fields. Moderate or severe nerve fiber layer atrophy at baseline was associated with a seven to eight times greater risk of development of visual field loss. Attributes that were significantly associated with the incidence of field loss included older age, larger cup-disc ratio, smaller rim-disc area ratio, larger cup asymmetry, presence of disc crescent, and higher intraocular pressure. Characteristics found not to be associated with incidence were gender, race, hypertension, diabetes, refractive error, family history of glaucoma, smoking or alcohol drinking history, and disc area. CONCLUSIONS: Increasing nerve fiber layer atrophy judged by a semiquantitative grading system was associated with increasing risk of development of visual field loss among persons with ocular hypertension. The relationship of the development of field loss to race, myopia, family history of glaucoma, and medical history are more complex than has been presumed.
Intranasal administration of an inoculum of 10(7) focus-forming units (FFU) of respiratory syncytial (RS) virus induced disease in BALB/c mice with signs of anorexia, cachexia, ruffled fur, and pneumonia. Mice displayed mild signs of illness on day 1 postinoculation (PI), followed by a transient recovery phase of 3 days. Disease rapidly reappeared on day 5 PI and worsened on subsequent days, with mortalities by day 7 PI. Mice inoculated with 5 x 10(6) FFU exhibited milder signs of disease, while those inoculated with 2 x 10(6) FFU and control mice given only Hep-2c cell suspension exhibited no noticeable signs of illness. High levels of bioactive tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected in both lungs and sera of mice inoculated with 10(7) FFU of virus. Peak levels of both cytokines were detected at day 1 PI but remained detectable throughout the 7 day period studied postinoculation. Cytokine levels were much lower or were undetectable in control mice. These results suggest that the macrophage is stimulated in vivo to produce inflammatory cytokines in response to RS virus infection.
An antisense approach was used to attempt to determine the function of the highly abundant, tapetum-specific A9 transcript in microsporogenesis. A Brassica napus A9 cDNA clone was linked in sense and antisense orientations to the Arabidopsis thaliana A9 promoter and the resulting chimaeric genes introduced into B. napus. A high proportion of the offspring of B. napus antisense A9 plants had very low or undetectable levels of A9 mRNA. However, these plants set seed and had pollen of normal or near normal viability. Therefore, under the conditions studied, the A9 protein appears not to be essential for male fertility in B. napus.
Amyloid deposits in Alzheimer's disease, Down's syndrome and aged brain are composed largely of A beta protein, which is generated by proteolytic processing of beta-amyloid precursor protein. Proteases responsible for liberating the A beta protein from the precursor have not yet been identified. Here, we examined the ability of cathepsin G, a chymotrypsin-like protease, to cleave two protease substrates: (i) a fluorogenic hexapeptide, whose sequence spans the cleavage site in the precursor for generating the A beta NH2-terminus, and (ii) recombinant human beta-amyloid precursor protein purified from a baculovirus expression system. Unlike two other members of the chymotrypsin family, cathepsin G readily degraded the hexapeptide. Furthermore, cathepsin G cleaved the beta-amyloid precursor protein to generate several breakdown products, including a prominent 11,500 mol. wt fragment immunoreactive with antibodies directed against the COOH-terminus of the protein. This COOH-terminal fragment co-migrated using two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis with C-100, a recombinant COOH-terminal segment of the beta-amyloid precursor, whose NH2-terminus is one residue upstream of the NH2-terminus of the A beta domain. We also examined the localization of cathepsin G in human brain. The distribution of cathepsin G-containing cells was examined by immunohistochemistry in the temporal cortex of both Alzheimer's and aged control samples. Cathepsin G-like immunoreactivity was contained specifically within neutrophils. As visualized by double-labeling with antibodies to cathepsin G and Factor VIII, neutrophils were most frequently found within meningeal or cortical blood vessels. In addition, occasional neutrophils could be identified without an apparent vascular surround, in the brain parenchyma. By simultaneous labeling with antibodies to cathepsin G and A beta protein, neutrophils were also sometimes found associated with both parenchymal and vessel amyloid deposits; however, these associations were rare. These findings indicate that cathepsin G is capable of cleaving the beta-amyloid precursor protein to liberate the free NH2-terminus of the A beta protein and may have access to areas where this material is deposited in Alzheimer's disease. However, since there is no physical association between neutrophils and deposited amyloid and no increase in the number of neutrophils in an Alzheimer's brain, cathepsin G seems to be an unlikely mediator of amyloid deposition in this disease.
The source of wear debris in total hip arthroplasty may occur at various interfaces: metal-ultra-high molecular-weight polyethylene bearings, metal-cement micromotion, bone-cement interfaces, and implant coatings. Wear-induced osteolysis may result in a spectrum of radiographic changes from radiolucent lines to massive osteolysis. Subsequent loosening of the implant may occur and revision may be difficult because of bone deficiencies. Impingement of the femoral neck on the acetabular component may result in polyethylene and/or metal debris, leading to early femoral stem loosening. The five cases presented, involving six hips, illustrate how bipolar cup-stem impingement may result in significant wear-induced femoral osteolysis.
In a community survey of 873 persons aged 70 years or over, focusing on dementia, cognitive decline, depression, and current life circumstances, we included an enquiry into the emotional impact of the interview. A large majority reported at the end of the interview that it had no adverse effect on their emotional state. About 4% reported that it made them distressed, 1% that it depressed them, and 2% that it had intruded on their privacy. By contrast, 52% said it had made them feel good about themselves. Distress seemed to be largely related to performing poorly on cognitive tests. There is no information on the duration of these effects in the period following the interview. It is recommended that respondents in community surveys, including the elderly, be informed that they can decline to answer any question, and that interviewers be trained in how to respond to the few who will be distressed by the experience.
In a community survey, subjects and their informants were asked the same questions about memory and intellectual decline in the subjects. Subjects and informants both commonly reported cognitive decline, although in most cases the decline was not seen as interfering with daily life. However, when responses from subjects and informants were cross-tabulated, agreement was found to be poor. For subjects, reports of cognitive decline were correlated with anxiety and depression symptoms and with trait neuroticism. Subjects' reports were uncorrelated with age and only weakly correlated with cognitive test performance, indicating little validity. By contrast, informants' reports were correlated with the subjects' cognitive test performance and age, but also with the informants' own anxiety and depression symptoms. Although informants' reports have validity, they may also be contaminated by the informants' affective state.
An 18-item inventory designed by Goldberg et al. (1987) to detect symptoms of anxiety and depression was administered to an elderly general population sample. Latent trait analysis was used to assess the dimensionality of the inventory and the location and discriminatory ability of the symptoms. The items showed different patterns of discrimination in this group compared to the sample of general practice attenders on which the inventory was developed. Overall, the items did define two correlated dimensions of anxiety and depression. In addition, a third dimension of sleep disturbance was detected. Both individual scales and the total symptom scores were sensitive and relatively specific detectors of depressive disorders assessed according to ICD-10 and DSM-III-R criteria. The retention of sleep items on their original scales did not affect the sensitivity of the scales to detect depressive disorders. A two-step administration procedure suggested for use in the administration of the scales was investigated but found to be sensitive to differences between the current sample and the sample on which the inventory was developed. This symptom inventory can be recommended for use in epidemiological investigations as a brief, valid and acceptable method of detecting elevated levels of anxiety and depression in elderly persons.
The purpose of our study was to investigate the extent to which the ratio between axial length and corneal radius (the AL/CR ratio) determines the refractive state of the human eye. Subjects for the study were 194 young adults between the ages of 18 and 30 years, whose spherical equivalent refraction ranged from +7.91 to -13.32 D. For each subject, manifest objective refraction, corneal radii, and axial ocular distances were measured. Lens power was determined using a formula proposed by Bennett and Rabbetts. The AL/CR ratio was found to be approximately 3.00 for emmetropic eyes, ranging from 2.60 for the most highly hyperopic eye to 4.10 for the most highly myopic eye. The coefficient of determination of linear regression for the AL/CR ratio as a function of spherical equivalent refraction was 0.84, suggesting that 84% of the variance in refraction could be accounted for by variance of the AL/CR ratio. The results of the study suggest that for a given amount of ametropia, an eye having a relatively high AL/CR ratio would tend to have a low-powered lens (indicating that the lens had "emmetropized"), whereas an eye having a relatively low AL/CR ratio would tend to have a high-powered lens. We conclude that the AL/CR ratio can provide information concerning the extent to which the lens has emmetropized by reducing its power concurrent with axial elongation.
Cancers of the colon and the rectum are the second leading cause of malignancy in European countries with similar incidence rates for men and women and, therefore, one of the major health concerns. Emphasis is placed on the early detection of a developing neoplasm in order to improve the life expectancy of patients and their quality of life. Colorectal cancer (CRC) is an excellent model for studying the etiology and pathogenesis of a common malignancy and the complex multistage process of carcinogenesis. Abundant clinical and pathological evidence suggests that CRC arises from benign adenomas that proceed through a series of steps to metastatic carcinomas. Following the discovery of oncogenes and, more importantly tumor suppressor genes, Fearon & Vogelstein (1990) proposed a scheme of genetic events which are associated with colorectal tumorigenesis. Genetic linkage studies have recently identified another type of gene for colon cancer susceptibility that seems to act by destabilising the genome.
Cross-cultural applications of Rorschach's test assume that American norms may be applied, but this assumption has little empirical basis. In fact, several such investigations have indicated that culture-specific norms must be employed on key variables employed to assess subjects' perceptual accuracy. The current study compared responses of 19 Spanish children who scored low on a reading measure and were considered by their teachers to experience significant reading problems with 19 peers who scored significantly higher on that reading measure and who experienced no apparent reading problems. Perceptual accuracy of both groups, as measured by the F+ and X+ percents, was virtually identical. Results are discussed in the context of other research which has questioned the cross-cultural applicability of American norms with respect to perceptual accuracy.
OBJECTIVES: Based on a community sample, to assess the reasons disabled elderly people need care, the type of formal services they receive, the characteristics of their carers and the degree of psychological morbidity in these carers. DESIGN AND SETTING: A community survey of people aged 70 or more years living in Canberra or Queanbeyan. Survey participants were asked to nominate informants, who were interviewed about the subjects' state of health. The informants provided information on need for care, services received and the role of carers. Informants also reported on their own health, including symptoms of anxiety and depression. RESULTS: Elderly people needed care because of physical disability more often than behavioural disability. Those with physical disability received more formal services and more help from health professionals than those with behavioural disability. Contact with general practitioners was high for both disabled and non-disabled subjects. Carers of the physically disabled had raised levels of anxiety and symptoms of depression, and poorer self-rated health, but carers of the behaviourally disabled did not. Wives, daughters and husbands made up the biggest categories of carers and around two-thirds of carers were women. CONCLUSION: Family carers play an important role in maintaining disabled elderly people in the community and this role is often stressful. Formal services have to be aimed as much at the needs of the carers as at the disabled people themselves.
The collagen fibres of rabbit and human ureter were exposed by digestion with trypsin and hyaluronidase. The fibre structure was examined using an SEM and examples of the inner and outer fibre structures are shown together with the effects of different types of mechanical strain. An interesting difference between the arrangements of the inner fibres of human and rabbit was seen where the human ureter had a cross-ply structure while in the rabbit it was helical.
The repair of interstrand crosslinks has been investigated in Fanconi anemia (FA) and normal cells as there is evidence suggesting that FA patients have a defect in DNA repair. Lymphoblasts were treated with the crosslinking agent mitomycin C (MMC) and the removal of the induced DNA lesions investigated at the level of the actively transcribed ribosomal RNA (rRNA) genes. MMC-induced crosslinks appeared to be a rather stable lesion in the rRNA genes for all cell lines studied. Variable repair efficiencies were found between the different cells lines but they could not be used to distinguish normal cells from FA cells. Therefore, we propose that the specific sensitivity of FA cells towards MMC cannot be directly correlated with a deficient repair in interstrand crosslinks and that probably the complexity of the repair process is greater than previously described.