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Biomedical subjects

D Irving

Publications and source records attributed to D Irving.

At least 19 recordsLinked to original sources
PubMed2002

Reduced oviposition of Boophilus microplus feeding on sheep vaccinated with vitellin.

The most abundant protein present in Boophilus microplus eggs, vitellin, was isolated and purified as a non-covalent complex of six glyco-polypeptides of Mr 44-107kDa. The protein complex bound haem. Immuno-blots demonstrated that antibodies raised to vitellin recognised a 200kDa polypeptide in the haemolymph of adult female ticks. This is consistent with the general proposal that in arthropods vitellin is derived by proteolytic processing from a large precursor protein, vitellogenin. In parallel with this study, an 80kDa glycoprotein (GP80) was independently purified from larvae of B. microplus using efficacy in vaccination trials as an assay. Antibodies to GP80 also recognised a 200kDa protein in the haemolymph of ticks and a major 87kDa polypeptide present in the vitellin complex. Conversely, antibodies to purified vitellin recognised GP80. The amino-terminal amino acid sequences of the 87kDa vitellin polypeptide and GP80 were identical for at least the first 11 residues and internal peptide sequences from both polypeptides were co-located in a single but incomplete deduced amino sequence of B. microplus vitellogenin. Thus, GP80 is a processed product from vitellogenin and highly related to but not completely identical with the 87kDa vitellin polypeptide. Vaccination trials in the model host sheep were performed with purified vitellin and GP80. Sheep vaccinated with either purified vitellin or GP80 returned significantly reduced numbers of engorged female ticks with decreased weights and reduced oviposition. In contrast, sheep vaccinated with recombinant hexahis-GP80, which was incorrectly folded and not glycosylated showed no significant effects on ticks. It was concluded that vitellin and GP80 could induce immune responses that partially protect sheep from the tick, B. microplus. However, critical protective epitopes are associated with the folding of the protein and/or the oligosaccharides attached to it.

Animals↗
PubMed1998

Effect of dietary catechin and vitamin E on aortic fatty streak accumulation in hypercholesterolemic hamsters.

Male golden Syrian hamsters were fed for 16 weeks on a hypercholesterolemic diet containing, per kg, 150 g of lipids (90 g butterfat, 35 g vitamin E-stripped corn oil and 25 g fish oil), 2 g cholesterol and either 3 IU vitamin E (3 IU E), 3 IU vitamin E and 200 mg catechin hydrate (3 IU E-200 Cat) or 30 IU vitamin E (30 IU E). More fatty streaks, measured by Oil Red O staining, were deposited in aortas of hamsters fed 3 IU E than in those fed either 3 IU E-200 Cat or 30 IU E. Lipid staining increased with plasma low-density lipoprotein cholesterol (LDL-C) in all animals. At the same concentration of LDL-C, animals fed either 3 IU E-200 Cat or 30 IU E developed less fatty streaks than those fed 3 IU E. Plasma LDL-C and total cholesterol were highest in hamsters fed 3 IU E and LDL-C and total cholesterol in animals fed 3 IU-200 Cat were not different from those fed either 3 IU E or 30 IU E. This study showed the importance of circulating plasma LDL-C on atherogenesis and the inhibitory effect on this process of both dietary vitamin E and catechin.

Animals↗
PubMed1996

Prognostic characteristics of surgical stage I endometrial adenocarcinoma.

PURPOSE: To evaluate and correlate the expression of pathologic characteristics, flow cytometric DNA content analysis, and estrogen and progesterone receptor levels with survival in patients with surgical Stage I endometrial carcinoma. METHODS AND MATERIALS: Hospital tumor registry records were surveyed, and this identified 232 patients diagnosed with endometrial adenocarcinoma between July 1, 1989, and December 30, 1993. DNA content analysis was performed on either paraffin-embedded or fresh tissue samples. Survival was calculated from the date of diagnosis by the Kaplan-Meier method. Postoperative irradiation (whole pelvis external beam therapy and low dose rate vaginal cuff brachytherapy) was delivered to patients felt to be at high risk for failure. RESULTS: One hundred seventy-one patients had Stage I tumors and were available for analysis. Patients with Stage 1C tumors had a statistically significant lower survival rate compared to patients with Stages IA or IB (p = 0.03 and p < 0.01, respectively). Patients with DNA content diploid tumors had a slightly increased (but nonsignificantly so) survival compared to patients with non-DNA content diploid tumors (p = 0.12). Logistic regression analysis failed to identify an independent prognostic factor that could predict for disease specific survival in patients with Stage I cancers. CONCLUSION: Logistic regression analysis did not identify a single independent prognostic factor in patients with Stage I tumors. Pathologic characteristics reported to predict survival advantage correlated with pathologic stage. Additional translational research is needed to identify molecular characteristics of tumors that may indicate more aggressive treatment for patients at high risk for recurrence.

Adenocarcinoma↗
PubMed1996

Clinicopathologic correlation of DNA flow cytometric content analysis (DFCA), surgical staging, and estrogen/progesterone receptor status in endometrial adenocarcinoma.

DNA flow cytometric content analysis (DFCA) and estrogen (ER) and progesterone (PR) receptor levels are reported to be prognostic with regard to the malignant potential of endometrial adenocarcinoma. We retrospectively reviewed the records of 50 patients presenting with endometrial adenocarcinoma between July 1990 and December 1992, to determine the extent of any pathologic features reported at the time of hysterectomy. Patients whose tumors were nondiploid (aneuploid) by flow cytometry generally presented with a higher pathologic stage, higher grade, and more frequent lymph node involvement. In addition, the majority of clear cell and uterine papillary serous (UPS) adenocarcinoma were also nondiploid. Fourteen of 21 ER-positive tumors aneuploid, as were 18 of 37 PR-positive tumors. We also found DNA-A (DNA content aneuploid) patterns frequently associated with tumor characteristics implicated by other authors as related to aggressiveness. Further studies comparing the molecular biology of tumors to their clinicopathologic features and behavior are needed to fully understand the ultimate malignant potential.

Adenocarcinoma↗
PubMed1995

Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.

High-affinity nicotine binding, considered to primarily reflect the presence of CNS alpha 4 beta 2 nicotinic receptor subunits, was examined autoradiographically in brain regions most severely affected by Alzheimer and Parkinson types of pathology. In the midbrain, the high density of binding associated with the pars compacta of the substantia nigra was extensively reduced (65-75%, particularly in the lateral portion) in both Lewy body dementia and Parkinson's disease. Since loss of dopaminergic neurons in Lewy body dementia was only moderate (40%), loss or down-regulation of the nicotinic receptor may precede degeneration of dopaminergic neurons in this region. In the dorsolateral tegmentum, where diffuse cholinergic perikarya are located, nicotine binding was highly significantly decreased in both Lewy body dementia and Parkinson's disease with almost no overlap between the normal and disease groups, indicative of a major pathological involvement in or around the pedunculopontine cholinergic neurons. In the hippocampus, binding was decreased around the granular layer in Lewy body dementia and Alzheimer's disease, although unchanged in the stratum lacunosum moleculare, where binding was relatively higher. Dense bands of receptor binding in the presubiculum and parahippocampal gyrus--areas of highest binding in human cortex--were diminished in Alzheimer's disease but not Lewy body dementia. In temporal neocortex there were reductions in Alzheimer's disease throughout the cortical layers but in Lewy body dementia only in lower layers, in which Lewy bodies are concentrated. Abnormalities of the nicotinic receptor in the diseases examined appear to be closely associated with primary histopathological changes: dopaminergic cell loss in Parkinson's disease and Lewy body dementia, amyloid plaques and tangles in subicular and entorhinal areas in Alzheimer's disease. Loss or down-regulation of the receptor may precede neurodegeneration.

Acetylcholinesterase↗
PubMed1994

Flow cytometric DNA content analysis of paraffin-embedded tissue derived from cervical carcinoma.

PURPOSE: Flow cytometric deoxyribonucleic acid (DNA) content analysis has been shown to be of prognostic importance in some cancers. There have been recent reports of a prognostic importance for DNA content analysis in cervical carcinoma. METHODS AND MATERIALS: We retrospectively reviewed the hospital and radiation oncology records of cervical carcinoma patients who presented between 1984-1990. RESULTS: A total of 101 archival paraffin-embedded blocks were processed, of which 77 were of technical quality for analysis. Thirty-five percent were found to be DNA content aneuploid (DNA-A) and 65% DNA content diploid (DNA-D). No statistical difference was found between the two groups in age at diagnosis, % S-phase, coefficient of variation (CV), or proliferative index (PI). A statistical difference was noted in the G2M phase between the two groups (p = 0.004). The median % S-phase was 8.4% in the DNA-D group. A statistical difference (p = 0.017) in survival was noted between the low and high % S-phase DNA-D groups. In patients who received radiation alone, high-PI patients had improved survival compared to low-PI patients. No statistical difference in survival was noted in the high % S-phase DNA-D group and DNA-A group (p = 0.28). Proportional Hazard (Cox) Regression found clinical stage the only independent prognostic indicator for survival. CONCLUSION: Flow cytometric DNA content analysis is being used more frequently in the management of different malignant tumors. Our study shows that DNA content analysis is useful in determining the prognosis and survival outcomes in cervical carcinomas and may aid in predicting outcome to certain types of treatment regimens.

Aneuploidy↗
PubMed1993

Monoaminergic activities in Lewy body dementia: relation to hallucinosis and extrapyramidal features.

Serotonergic (5-HT) and dopaminergic activities have been examined in Lewy Body Dementia (LBD) and compared with Parkinson's disease (PD) and Alzheimer's disease (AD). In the neocortex the LBD subgroup experiencing hallucinations was distinguished from the other categories by an increase in the 5HIAA:5HT ratio measured in frontal cortex and by the serotonergic (5-HIAA or 5-HIAA:5-HT): cholinergic (choline acetyltransferase) ratio in frontal and temporal cortex. In the neostriatum (caudate nucleus), loss of dopamine and increased HVA:dopamine ratio correlated with the reduction in substantia nigra neurons in LBD but not PD, despite the greater loss of neurones and dopamine and the higher dopamine turnover ratio in PD. LBD patients experiencing severe Parkinsonism as a result of neuroleptic treatment tended to have lower neuron counts, in combination with higher turnover ratios, than the remainder. Qualitative differences between LBD and PD included decreased cortical 5-HT turnover in PD compared with the increase in LBD. There were no significant changes in any parameter in AD, with the exception of a reduction in temporal cortex 5HIAA. The results suggest that although the neurochemical pathology of LBD and PD involves similar systems, the nature of the derangements differs sufficiently between the diseases to account for differences in symptomatology.

Aged↗
PubMed1993

Detection of Lewy bodies in Trisomy 21 (Down's syndrome).

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a clinico-neuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Adult↗
PubMed1993

Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease.

Senile dementia of Lewy body type or Lewy body dementia (LBD), characterized neuropathologically by the presence of Lewy bodies in the brainstem and cortex, and in most cases neocortical senile plaques (but few or no tangles), bears a closer resemblance to Parkinson's (PD) than to Alzheimer disease (AD) in its cholinergic neurochemical pathology. Thus, reductions in the biochemical activity of choline acetyltransferase were generally more extensive in neo- as opposed to archicortical regions in LBD (especially hallucinating cases) and in PD, whereas muscarinic receptor binding was significantly increased in LBD and PD but not in AD. Nerve growth factor receptor (P75) assessed immunocytochemically in the archicortex were decreased in PD and, to a lesser extent, in LBD in conjunction with reductions of neuronal numbers in the nucleus of Meynert (Ch4), but were relatively spared in AD. These observations indicate that although AD is primarily associated with dysfunction of cholinergic axonal input to the cortex, LBD and PD are more likely to involve degeneration of the basal forebrain cholinergic system. Relevance of the findings in terms of aetiopathology and cholinergic treatment strategies is discussed.

Aged↗
PubMed1992

The 42-kilodalton rhoptry-associated protein of Plasmodium falciparum.

The gene coding for a 42-kDa rhoptry protein of Plasmodium falciparum has been cloned. On the basis of prior monkey vaccination studies, this protein is regarded as an important vaccine candidate, but its identity has been the subject of considerable uncertainty. Analysis of the cloned sequence shows that it is a basic, hydrophobic protein, without repetitive elements, unrelated to any of the previously postulated gene products and shows minimal sequence diversity. The availability of the corresponding recombinant protein will enable studies of its efficacy in human vaccine trials to be undertaken.

Amino Acid Sequence↗
PubMed1991

Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients.

A Lewy body dementing syndrome in the elderly has been recently described and designated senile dementia of Lewy body type (SDLT) on the basis of a distinct clinicopathological profile. The pathological changes seen in SDLT include the presence of cortical Lewy bodies (LB) frequently, but not invariably, associated with senile plaque (SP) formation. Whilst neocortical neurofibrillary tangles (NFT) are sparse or absent, a proportion of these cases show involvement of the temporal archicortex by lesions comprising Alzheimer-type pathology (ATP, i.e. NFT, SP and granulovacuolar degeneration [GVD]). Thus the relationship between SDLT and senile dementia of Alzheimer type (SDAT) is complex and controversial. In this study quantitative neuropathology was used to compare the intensity and distribution of ATP in the hippocampus and entorhinal cortex of 53 patients from 3 disease groups (SDLT, SDAT, Parkinson's disease (PD)) and a group of neurologically and mentally normal elderly control patients. For most brain areas examined the extent of ATP between the patient groups followed the trend SDAT greater than SDLT greater than PD greater than control. Statistical comparison of these groups revealed significant differences between the mean densities of NFT, SP and GVD although individual cases showed considerable variability. These results confirm additional pathological differences between SDAT and SDLT regarding the intensity of involvement of the temporal archicortex by ATP. Many patients with Lewy body disorders (LBdis) show a predisposition to develop ATP albeit in a more restricted distribution (e.g. low or absent neocortical NFT) and at lower densities than is found in SDAT. Some cases of SDLT show minimal SP and NFT formation in both neocortex and archicortex supporting previously published data distinguishing this group from Alzheimer's disease.

Aged↗
PubMed1991

Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson's disease, and Alzheimer's disease.

Cholinergic and monoaminergic (dopaminergic and serotonergic) activities have been examined in postmortem brain tissue in senile dementia of Lewy body type, Parkinson's disease, and Alzheimer's disease. Quantitative data suggest that although extrapyramidal symptoms relate to striatal levels of dopamine, cognitive impairment is most closely associated with cholinergic (but not monoaminergic) deficits in temporal and archicortical areas. Hallucinations, which are most frequent in Lewy body dementia, appear to be related to an extensive cholinergic deficit in temporal neocortex and the resulting imbalance between decreased cholinergic and relatively preserved serotonergic activities. Topographic analyses such as these including consideration of quantitative "threshold" effects, may be relevant to the future anatomic focus of neurochemical investigations in dementia and to the development of appropriate experimental models.

Adult↗
PubMed1990

Use of Gianturco self-expandable stents in the tracheobronchial tree.

Gianturco self-expandable stents were used successfully in the management of 5 patients with tracheobronchial pathology. Placement was performed under endoscopic and fluoroscopic guidance. None of the patients has experienced complications secondary to the stent placement, and in all of them the clinical problems resolved satisfactorily. Longer follow-up is required to determine the place of tracheobronchial stenting in patients with respiratory compromise.

Aged↗
PubMed1990

Lewy body prevalence in the aging brain: relationship to neuropsychiatric disorders, Alzheimer-type pathology and catecholaminergic nuclei.

In a survey to determine the occurrence of Levy bodies in the elderly, the prevalence rate of Lewy body formation was found to be critically dependent on the psychiatric status of control cases. In 131 controls between 51 and 100 years screened to exclude psychiatric and neurological disorders, the Lewy body prevalence rate was 2.3%, but inclusion of cases with psychiatric disorders other than Alzheimer's disease increased the prevalence rate to 9%. An age-related decline in substantia nigra and locus coeruleus neuron numbers was observed in the control group. Brain stem Lewy body formation (found in 3 cases) was not necessarily linked with neuron loss in substantia nigra, though in two of the cases significant locus coeruleus neuron loss was observed. Within the control group, there was no obvious relationship of Lewy body formation to the extent of Alzheimer-type pathology. These findings are compatible with the disease specificity of Lewy bodies and suggest that Lewy body disorders have a relatively short preclinical phase in which Lewy body formation may precede both locus coeruleus and substantia nigra neuron loss. The increase of Lewy body positive cases found when individuals with psychiatric disorders are included in the population surveyed supports the emerging concept of a spectrum of Lewy body diseases ranging from purely psychiatric disorders through combined psychoneurological or neuropsychiatric symptoms, to the classically described neurological disorders of Parkinson's disease.

Aged↗
PubMed1990

Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly.

A dementing syndrome has been identified in a group of psychiatric cases aged 71-90 years, presenting initially with a subacute/acute confusional state, often fluctuating and associated with visual hallucinations and behavioural disturbances. Clinically, these cases did not meet criteria for a diagnosis of Alzheimer's disease, and many were assigned to the multiinfarct dementia group, although no significant ischaemic lesions were evident at autopsy. Mild extrapyramidal features were apparent in a number of cases but the characteristic clinical triad of Parkinson's disease, i.e., tremor, rigidity, and akinesia, was absent. Detailed neuropathological examination revealed Lewy body formation and selective neuronal loss in brain stem and other subcortical nuclei, accompanied by Lewy body formation in neo- and limbic cortex, at densities well below those previously reported in diffuse Lewy body disease. A variable degree of senile degenerative change was present; numerous senile plaques and minimal neurofibrillary tangles in most cases. Neither the clinical nor the neuropathological features of this group are typical of Parkinson's or Alzheimer's disease, but suggest a distinct neurodegenerative disorder, part of the Lewy body disease spectrum, in which mental symptoms predominate over motor disabilities and lead to eventual psychogeriatric hospital admission. In a sequential series of autopsies conducted on clinically assessed demented patients, neuropathological analysis has indicated that such cases may comprise up to 20% of a hospitalized population of demented old people over the age of 70 years, an observation clearly relevant to the diagnosis and management of dementia in the elderly.

Aged↗