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Biomedical subjects

D O'Neill

Publications and source records attributed to D O'Neill.

At least 127 records · Page 7Linked to original sources

Evaluation of the PEP mask in cystic fibrosis.

Twenty-eight patients suffering from cystic fibrosis, with an age range of 8-21 years entered a randomised cross-over trial to study the efficacy of the Positive Expiratory Pressure (PEP) mask as a method of chest physiotherapy, both on its own and in conjunction with other physiotherapy techniques. Twenty-four of these patients completed the trial consisting of 4 treatment programmes each lasting one month and with no wash-out period between them. Five of these patients went on to a fifth programme of Forced Expiratory Technique (FET) alone. At the end of the trial, no significant difference was found between the programmes as regards growth, Shwachman score, Chrispin-Norman score or pulmonary function tests. Twenty-three patients chose to continue using the PEP mask in conjunction with FET long-term as their chest physiotherapy programme as they felt it was an effective treatment allowing increased independence, with postural drainage being kept to a minimum.

Adolescent↗

Pulmonary peptides, norepinephrine and endocrine cells in monocrotaline pulmonary hypertension.

The concentrations of norepinephrine and of the peptides bombesin, calcitonin gene-related peptide and neurotensin were measured in rats with monocrotaline pulmonary hypertension. The numbers of pulmonary endocrine cells showing positive immunoreactivity for calcitonin, calcitonin gene-related peptide, protein gene product 9.5 and bombesin were counted in a second group of rats with monocrotaline pulmonary hypertension. The concentration of norepinephrine in the lungs decreased significantly in the test rats but this could be attributed to dilution by an increased mass of tissue. The pulmonary concentration of all three peptides showed a decrease in the rats treated with monocrotaline but this was highly significant only in the case of bombesin. The pulmonary content of bombesin showed a substantial and significant decrease in the test rats. No neuroendocrine cells immunopositive for bombesin were identified in any of the control or test rats. There was no difference between the control and test rats with respect to the form or distribution of the cells immunoreactive for the other three The lack of pulmonary endocrine cells showing immunoreactivity for bombesin may be related to the absence of intimal proliferation in the pulmonary arteries in this species. This is in striking contrast to what occurs in plexogenic pulmonary arteriopathy in man and suggests that monocrotaline-induced pulmonary hypertension in rats is not a good animal model for this disease.

Animals↗

Protein-DNA interactions upstream from the human A gamma globin gene.

We have used DNAase I footprinting and the gel mobility shift assay to study proteins which bind to promoter elements located between -140 and -382 upstream of the human A gamma globin gene. Footprints are found with both erythroid and nonerythroid nuclear extracts at three sites: from -294 to -264, -242 to -227, and -189 to -172 from the transcription initiation site. An erythroid-specific footprint is identified from -194 to -189. We demonstrate that two known transcription factors, the ubiquitous octamer-binding protein OTF-1 and the erythroid regulatory factor NFE-1, bind to the -194 to -172 region and that their footprints overlap. Binding of OTF-1 to this region is reduced by a mutation at -175 associated with a form of non-deletion hereditary persistence of fetal hemoglobin. We conclude that OTF-1 may compete with NFE-1 for the -175 binding site, possibly functioning as a repressor of gamma globin transcription.

Base Sequence↗

Elder abuse.

Elder abuse is an under-recognised cause of morbidity in the elderly. The frail elderly with multiple physical and psychiatric problems living with a relative who may also have a physical or psychiatric problem are particularly at risk. Although increased awareness of the problem and a high index of suspicion are necessary factors to diagnose the condition, clinical pointers towards diagnosis are available. Treatment for both victim and "carer" should be on the basis of multi-disciplinary assessment, and may result in admission of the elderly patient to an extended-care facility.

Aged↗

The effect of mild to moderate dementia on the Geriatric Depression Scale and on the General Health Questionnaire.

The Geriatric Depression Scale (GDS) and two versions of the General Health Questionnaire (GHQ 28 and corrected GHQ 28) were administered to 111 patients admitted to an acute geriatric medical unit. Depression and dementia were diagnosed by semi-structured interview using DSM III criteria. There was no statistically significant difference in the three scales between cognitively normal depressed patients and demented depressed patients. The three scales were sensitive indicators of depressive illness (greater than 90%), but the GHQ 28 and CGHQ 28 needed adjustment of their community-based threshold values.

Aged↗

The regulation of gamma-globin gene expression.

In summary, our analysis indicates that important sequences for the proper initiation of fetal gene transcription in fetal cells are located in the gamma-globin [sequence: see text] promoter. These sequences are sufficient for tissue-specific expression but not induction in K562 cells. Sequences in the gamma-globin IVS-2 and the beta-globin 3' enhancer increase gamma beta and gamma-Neo transcripts when cells containing these genes undergo erythroid maturation as measured by induction with hemin. The mechanism by which these sequences exert their effect remains to be elucidated. [see text] Multiple protein factors bind to both the gamma promoter and the beta 3' enhancer. Both of these regions contain binding sites for the erythroid-specific factor NFE-1 and the octamer binding factor OTF-1. In the gamma upstream region, there may be a competition between OTF-1 binding and NFE-1 binding that affects gamma gene regulation. Our results indicate that the beta 3' enhancer interacts with the gamma gene promoter to permit increased gamma gene expression. We have developed a model for globin gene switching that takes into consideration the effect of cis-acting sequences on globin gene transcription. A similar model of hemoglobin switching in chickens has been proposed by Choi and Engel. In our model, competition for the beta-globin 3' enhancer is involved in stage-specific transcriptional activation of gamma-globin genes in fetal cells and beta-globin genes in adult cells. In adult cells the protein-protein interactions between adult cell-specific factors interacting with the beta-globin promoter and erythroid-specific factors interacting with the beta 3' enhancer would activate transcription of the beta-globin gene. In fetal cells protein-protein interactions between fetal cell-specific factors interacting with the gamma-globin promoter and erythroid-specific factors interacting with the beta 3' enhancer would activate the transcription of the gamma-globin genes.

Base Sequence↗

Herniated lumbar disc in patients over the age of fifty.

Fifty patients ranging in age between 50-78 years (mean, 56) underwent surgery for a herniated lumbar disc between January 1986 and July 1988. All had objective clinical and radiographic evidence of a herniated disc. All had had failure during an appropriate period of conservative treatment. Far lateral herniation occurred in 8%, and 28% had disc herniations at L2 or L3. Surgical results were 64% excellent, 28% good, 6% fair, and 2% poor. Complications including urinary tract infection, wound infection, myocardial infarction, and pulmonary embolism were observed in 8% of patients. Lumbar disc herniation in the elderly is common. After thorough evaluation to exclude neoplasm or infection, decompression of neural structures can lead to 90% good to excellent results. Spinal stenosis must be carefully considered both preoperatively and intraoperatively. Also, a higher incidence of more cephalad lumbar herniations and far lateral herniations was observed in older patients.

Age Factors↗

Regulation of human fetal hemoglobin gene expression.

An understanding of the mechanism involved in the regulated expression of the human gamma and beta globin genes requires the detailed definition of the cis-acting DNA sequences and trans-acting protein factors responsible for their developmental stage specific expression. To determine the critical cis-acting elements, hybrid genes containing elements of the gamma and beta globin genes were transfected into K562 cells, a human erythroleukemia line. The regulated expression of the gamma and beta genes was also studied by transferring hybrid genes containing the gamma or beta promoters linked to the neomycin resistance gene (neoR) into erythroid (K562) cells and nonerythroid (Hela) cells. DNA sequences found to be important to the expression of the gamma gene were assayed for the presence of transacting factors by studying the binding of protein factors using the gel mobility shift assay. The results suggest that there are multiple cis-acting elements 5' and 3' to the gamma and beta genes, and perhaps within these genes contributing to their regulation. In addition, there are multiple trans-acting protein factors interacting with these regions which may determine their transcriptional regulation in erythroid cells.

Binding, Competitive↗

Screening for dementia and delirium using an adapted Folstein Mini-Mental State Examination.

An adapted Folstein Mini-Mental State Examination was applied to 244 consecutive admissions to an acute geriatric medical unit to determine the prevalence of cognitive impairment. At a cut-off point of 23/30, 109 (44%) were rated as normal and 44 (19%) were unable to perform the test. Of the 85 (36%) who scored less than 23, 63 were suffering from dementia, nine were delirious, and 12 had normal cognitive function, a false positive rate of 14%. The most common dementia was senile dementia of the Alzheimer type. Cognitive impairment was not noted by the admitting doctor in 57% of affected cases. The need for increased awareness of cognitive impairment in the elderly is emphasized, and the more widespread use of formal mental test scores is recommended.

Cognition Disorders↗