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Biomedical subjects

B McDonald

Publications and source records attributed to B McDonald.

At least 37 records · Page 2Linked to original sources
PubMed1998

Analysis of a human cDNA containing a tissue-specific alternatively spliced LIM domain.

A unique clone, isolated from a human pancreatic cDNA library, was sequenced and characterized. Northern blot analysis showed that the gene is active in a number of fetal and adult tissues, and immunoblots showed expression in nuclear and cytosolic cell fractions. The gene corresponding to the clone was localized to chromosome 13 by human/rodent somatic cell hybrid panels. The largest open reading frame contains a LIM domain, and the deduced peptide from the open reading frame appears to have the characteristics of a LIM-only protein, designated LMO7. RT-PCR and genomic sequence analyses indicate that expression of this gene product is subject to tissue-specific modulation by elimination of the LIM domain by alternative splicing in neural tissues.

Adult↗
PubMed1998

Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study.

In a post-mortem study of cerebral asymmetry in schizophrenia it was found that asymmetry of the length from the frontal pole to the central sulcus measured dorsally over the external surface of the brain on both hemispheres, showed a gender x diagnosis interaction (p = 0.002). Female controls had a left-greater-than-right asymmetry, and the male controls had a right-greater-than-left asymmetry. This pattern was reversed in schizophrenia. The converse effect was observed on a similar measure of the occipito-parietal lobes (p = 0.028). Significant changes were not seen in measures taken around the lateral surface of the hemispheres. Further, within the patient group, the frontal lobe asymmetry was related to age of onset such that leftward asymmetrical brains were associated with a later age of onset than rightward asymmetrical brains (p = 0.0463 for the females; p = 0.0162 for the males). The occipito-parietal asymmetry was not related to age of onset. We conclude that the asymmetry of the relative distribution of tissue between frontal and posterior regions of the hemispheres is altered in schizophrenia. The findings also suggest that there is an interaction between gender and cerebral asymmetry that is critical in determining age of onset.

Age of Onset↗
PubMed1998

Temporal-lobe length is reduced, and gyral folding is increased in schizophrenia: a post-mortem study.

This post-mortem study of the brains of 29 controls and 25 patients with schizophrenia investigated the length and gyral folding of the temporal lobes, and the asymmetries and inter-relationships of these two measures. The degree of gyral folding was significantly increased in schizophrenia (p = 0.002), but the orientation of the sulci was not changed (p = 0.420). Neither gender nor side affected any of the measures of gyral anatomy, nor were there any significant interactions of these variables with diagnosis. The temporal lobes were significantly shortened in schizophrenia, on two different measures (p = 0.009, and p = 0.001), and on one of these, females had shorter temporal lobes than males (p < 0.0005). No diagnosis x side interactions were found. The temporal-lobe shortening remained after controlling for brain weight and was not statistically related to gyral folding. These two structural changes may reflect an alteration of the cortico-cortical connectivity of the brain in schizophrenia.

Aged↗
PubMed1998

Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene.

The MLL gene is frequently rearranged in acute human leukemia of both the myeloid and lymphoid lineages. Using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we identified several abnormally spliced transcripts in which MLL exons were joined in an order different from the genomic orientation (scrambled exons). Mis-splicing of MLL was present in both normal and malignant tissues. Although the majority of these scrambled transcripts were joined accurately at consensus splice sites, there were several examples in which the junctions of exons spliced in aberrant order were at non-consensus sites. A number of features differentiate mis-splicing of MLL from the previously described cases of scrambled exons and circular RNAs. Some scrambled transcripts appear to be present in the polyadenylated fraction of RNA. No correlation of exon scrambling with exon skipping was found, and there was no particular tendency for the exons involved to be near large introns. Our data show that splicing of MLL is extremely complex. The presence of scrambled transcripts in both normal and leukemic cells, indistinguishable from transcripts resulting from genomic MLL rearrangements, precludes the use of nested RT-PCR as a screening method for detection of tandem duplication of tandem duplication of MLL.

Acute Disease↗
PubMed1998

Absence of aluminium in neurofibrillary tangles in Alzheimer's disease.

Using the new technique of nuclear microscopy, aluminium is not detected in pyramidal neurons in brain tissue from Alzheimer's disease (AD) patients. The analytical technique of nuclear microscopy can simultaneously image and analyse features in unstained and untreated tissue sections. In tissue which had been previously subjected to conventional procedures such as fixation and osmication, aluminium was observed in both neurons and surrounding tissue. This result shows that the analysis of tissue prepared using conventional chemical techniques may produce contamination or elemental redistribution, and supports our previous investigations which implied that aluminium is not involved in the aetiology of AD. In addition, significant increases in iron, phosphorus and sulphur concentrations were noted between neurons from Alzheimer tissue and neurons from age-matched controls, and between the supporting Alzheimer tissue and supporting control tissue, implying an overall increase in these elements. No significant increase in calcium was observed between neurons from Alzheimer tissue and neurons from age-matched controls.

Aluminum↗
PubMed1998

Worker health and safety training: assessing impact among responders.

A mail survey was conducted among emergency responders who received training at the New Jersey/New York Hazardous Materials Worker Training Center. Responses indicate that technical topics are extremely important (i.e., decontamination, personal protection); that the vast preponderance of trainees felt confident in their ability to recall specific critical concepts in a crisis; and that 42% of respondents (75) had experienced an incident that would have resulted in injury or death without training. Phone surveys for details of specific incidents reported by 43 of the 75 mail survey respondents revealed that anecdotal data provide powerful evidence of the value of training; that extensive and uniform training is needed across jurisdictions; that training should emphasize the technical aspects of health and safety, and should include demonstration and hands-on techniques; and that integrated organizational support for implementation of health and safety practices is critical.

Decontamination↗
PubMed1998

Temporal cortex synaptophysin mRNA is reduced in Alzheimer's disease and is negatively correlated with the severity of dementia.

We measured synaptophysin mRNA in neocortical tissue from 7 prospectively assessed, pathologically verified normal individuals, 17 subjects with Alzheimer's disease (AD), and 13 subjects with a non-AD dementia. In temporal cortex (Brodmann area 21), synaptophysin mRNA was decreased in AD and non-AD dementia groups compared to controls. The loss was also present relative to polyadenylated mRNA content. Synaptophysin mRNA signal correlated negatively with the degree of dementia and negatively with the pathological severity of AD. In occipital cortex (Brodmann area 17) there were no differences between groups nor clinicopathological correlations. These data extend the evidence for a regional synaptic pathology in AD which affects synaptic protein gene expression by temporal cortex neurons.

Aged↗
PubMed1998

Gene expression studies of mRNAs encoding the NMDA receptor subunits NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C, and NMDAR2D following long-term treatment with cis-and trans-flupenthixol as a model for understanding the mode of action of schizophrenia drug treatment.

It has been hypothesized that glutamate receptor function is important in both the aetiology and treatment of schizophrenia. In order to understand how specific glutamate receptor genes are involved in the treatment of schizophrenia we have used a multiprobe oligonucleotide solution hybridization (MOSH) technique to examine the regulation of gene express of the NMDAR1, 2A, 2B, 2C, 2D receptor subunits in the left rat brain following treatment with the optical isomers of flupenthixol. cis- and trans-flupenthixol are both present in the commonly used oral and depot treatments for schizophrenia and a controlled trial showed that cis-flupenthixol had a significantly superior ability to ameliorate the positive symptoms of schizophrenia compared to its trans-isomer. At a dose of 0.2 mg/kg/day over a period of 1, 2, 4, 8, 12 and 24 weeks, we found that both isomers down regulated the expression of NMDAR1 mRNA in most regions of the brain. NMDAR2A, 2B and 2C receptor subunits showed a significantly decreased expression from 12 to 24 weeks but after 2 weeks NMDAR2B, 2C, 2D expression was increased in several brain regions. The NMDAR1 receptor subunit immunoreactivity in the right brain following 4 and 24 weeks of drug treatment was also examined by Western blotting. Both trans- and cis-flupenthixol significantly decreased the NR1 immunoreactivity in the right cerebellum after 24 weeks of treatment. These results suggest that NMDA receptor subunits may have a role in the action of antipsychotic drugs. If we assume that the NMDA receptor expression changes reflect a beneficial and significant mechanism in the treatment of schizophrenia, it could be argued that NMDA receptor changes are more related to the negative or non-specific symptoms of schizophrenia.

Administration, Oral↗
PubMed1998

Electron microscopy study of explanted intraocular lenses from clinically noninfected eyes.

PURPOSE: To determine whether intraocular lenses (IOLs) in clinically noninfected eyes are coated with a significant, bacteria-containing biofilm. SETTING: The Oxford Eye Hospital, Oxford, United Kingdom. METHODS: Twenty-six IOLs, removed for reasons other than endophthalmitis from 26 patients attending the Oxford Eye Hospital over a 3 year period, were examined by electron microscopy. Immediately following explantation, the IOL was placed in glutaraldehyde 4% in 0.1 M phosphate buffer solution and processed for scanning electron microscopy (SEM). Areas of interest were reprocessed for transmission electron microscopy (TEM). RESULTS: There was no evidence of a bacterial biofilm on any IOL. In 5 IOLs, significant host cellular debris was seen at the tip of the haptic or at the optic-haptic junction. In 4 of them, clusters of coccoid-shaped structures were seen at the optic-haptic junction on SEM, but examination by TEM showed these structures to be melanosomes, not bacteria. CONCLUSION: We found no evidence to suggest that a significant number of IOLs are coated with a bacterial biofilm in clinically noninfected cases. We advocate the use of TEM to distinguish between coccoid bacteria and melanosomes.

Adult↗
PubMed1998

Comparison of pathological diagnostic criteria for Alzheimer disease.

Because the clinical picture of Alzheimer disease (AD) is often difficult to discriminate from other dementing illnesses, the diagnosis of AD requires neuropathological confirmation. However, for the pathological diagnosis of AD, there are no unanimously accepted criteria. The three currently used sets of pathological criteria (Khachaturian: Khachaturian, Arch Neurol 1985;42:1097-105; Tiemy: Tierney et al., Can J Neurol Sci 1986; 13:424-6; CERAD: Mirra et al., Neurology 1991;41:479-86) for the disease differ from each other considerably. We applied these criteria to the first 43 consecutive subjects (37 demented) with no neuropathology other than AD-type pathology from autopsies after longitudinal prospective clinical study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). The results show that the CERAD category of definite AD corresponds closely with the cases that fulfill Tierney A3 inclusion criteria for AD. The combined CERAD categories of possible, probable, and definite AD correspond closely to cases fulfilling Khachaturian criteria forAD. The influence of a clinical diagnosis of dementia when Khachaturian and CERAD criteria were applied was considerable because between 9.3% and 90.7% of patients would have been categorized differently depending on whether clinical dementia was present or absent.

Aged↗
PubMed1997

Primary (localised non-familial) conjunctival amyloidosis: three case reports.

Conjunctival amyloidosis is an uncommon condition which usually arises secondary to chronic infection or trauma to the eye. It is rare to find significant deposits of amyloid involving the conjunctiva alone in the absence of a known antecedent infective, traumatic or hereditofamilial disorder. We report three patients with primary localised conjunctival amyloidosis. Each patient presented with a painless swelling in the lower fornix; in two this gradually extended to involve the bulbar and palpebral conjunctiva of both eyes with friable yellow deposits. Detailed clinical photographs illustrate the specific features of the disease. None of the patients had previous ocular pathology and bacterial, viral and fungal cultures of the conjunctiva were negative. There were no signs of inflammation. Conjunctival biopsies in each case showed large amorphous nodular deposits of amyloid within the substantia propria. Extensive systemic investigations including serum and urinary protein immunoelectrophoresis were normal. Follow-up ranged from 2 to 15 years after presentation. Treatment was symptomatic. As the typical features of amyloidosis present late in the course of conjunctival disease a diagnostic biopsy is often delayed. Once there is histopathological verification plasma cell disease must be excluded, although if the amyloid is limited to the conjunctiva systemic involvement is unlikely.

Aged↗
PubMed1997

Electron microscopy findings on an intraocular lens in the uveitis, glaucoma, hyphaema syndrome.

PURPOSE: To report the electron microscopic findings on an explanted intraocular lens in a patient with the uveitis, glaucoma, hyphaema syndrome. METHODS: Scanning and transmission electron microscopy were undertaken on a coccoon of cellular material from the tip of the intraocular lens haptic. RESULTS: Scanning electron micrographs showed densely packed coccoid-like structures on the haptic surface. By transmission electron microscopy these structures proved to be melanosomes. CONCLUSIONS: The scanning electron micrographs described in this report are similar to those reported in patients with chronic post-operative uveitis, but to our knowledge have not been shown before in association with the uveitis, glaucoma, hyphaema syndrome. Transmission electron microscopy determined that the coccoid-like structures were melanosomes. The melanosomes are probably derived from damaged pigment epithelial cells or iris stromal melanocytes secondary to recurrent chafing of the haptic against the posterior surface of the iris.

Aged↗
PubMed1997

Benign intracerebral cysts with ependymal lining: pathological and radiological features.

Cerebral intraparenchymal cysts without communication with the ventricles are very rare. We report four such cases with no relevant past history or evidence of infection, haemorrhage, trauma, tumour or congenital neural tube defect. At operation smooth wailed cysts with an ependymal-type lining were found. To the best of our knowledge, we present the first correlation of their pathological and radiological features (including magnetic resonance imaging). We also review the literature on these cysts.

Adult↗
PubMed1997

The effects of additional pathology on the cognitive deficit in Alzheimer disease.

The diagnosis of Alzheimer disease (AD) according to current criteria is a combined clinical and pathological exercise. The clinical discrimination of AD from other types of dementia may be complicated when the patient suffers from more than one disease. In particular the concomitant presence of other neurological conditions may significantly influence the severity of cognitive deficit. In this study we analyze the extent of the influence of vascular and other neurodegenerative pathology on the cognitive deficit in a consecutive series of 88 prospectively assessed elderly subjects. We find that, for any given level of cognitive deficit, the densities of either all plaques or neuritic plaques alone in the neocortex are significantly lower in cases of AD mixed with other CNS pathology than in cases of AD with no other CNS pathology. In AD combined with cerebrovascular disease, the total plaque density makes a significant contribution to cognitive deficit, while neurofibrillary tangle (NFT) densities do not. In contrast, in pure AD tangle density is the major determinant of cognitive deficit. Our findings draw attention to the influence of coexisting brain pathologies on the clinical manifestation of dementia in subjects with AD. These findings indicate that pathological diagnostic criteria for AD should take into account such additional pathology in demented subjects. They also improve understanding of the circumstances in which the amyloid component of AD can play a decisive role in precipitating clinical dementia.

Aged↗
PubMed1997

The health of Filipinas in the Hunter region.

An interview survey found life-style behaviours (including risk factors and screening), social support and psychological health (GHQ-12) among a sample of 198 Filipina-Australians to be conducive to good health. Knowledge of local health services was good, and most women expressed general satisfaction with all aspects of life in Australia, except in the area of employment prospects. Despite these indications of good health in the group, there remains a need for health service providers to be aware of the difficulties faced by a proportion of Filipina migrants to Australia.

Adult↗
PubMed1997

Adaptation to the mental health setting: the lived experience of comprehensive nurse graduates.

The aim of this qualitative descriptive study was to explore the experience of new comprehensive nurse graduates as they adapted to working in the acute psychiatric setting. Interviews were conducted with four participants, focusing on their current work experiences and how the philosophical beliefs and values derived from their educational preparation fit with those they encountered within the practice setting. The data were analysed by noting common experiences, values and meanings and identifying the themes that emerged. The themes were: transition to practice, conflict, contradiction, structural constraints, and the 'reality' of the psychiatric setting. The results of the study confirm the concern that has been voiced by new graduates about the quality and quantity of current orientation programs. Conflicting values and beliefs concerning the nature of mental health/psychiatric nursing also became evident. It appears that the graduates' Comprehensive nursing preparation may have contributed to their feelings of unease as they attempted to fit their own values and beliefs about nursing with those of the acute psychiatric setting.

Adaptation, Psychological↗
PubMed1996

Ultrastructural study of the cornea in a bone marrow-transplanted Hurler syndrome patient.

This case report describes a 14-year-old girl with Hurler syndrome, who had received a successful bone marrow-transplant at the age of two. Corneal clouding was present at the time of transplant and has only partially cleared. A right penetrating keratoplasty was performed and the corneal specimen was examined by light microscopy, transmission electron microscopy with Cuprolinic blue staining for proteoglycans, and low-angle X-ray diffraction. The results show the corneal stroma to be disrupted by vacuolated stromal cells. There is abnormal accumulation of proteoglycans in the vacuolated stromal cells and nearby stroma. These proteoglycans mainly contain chondroitin/dermatan sulphate glycosaminoglycans since they are susceptible to chondroitinase ABC. There are a large range of fibril diameters (12.5-50.1 nm) and there is an abnormal distribution of the fibril diameters measured from micrographs. Both are confirmed by X-ray diffraction results (the mean collagen fibril diameters are in a range between 29.7 and > 51.1 nm). X-ray diffraction also shows that the mean centre-to-centre distance of the fibrils slightly increases. These findings suggest that proteoglycans play a role in modelling the stromal structure and can also explain the corneal clouding. Many long-spacing collagen structures with a mean periodicity of 91.8 nm are observed in the corneal stroma. The finding that the long-spacing collagen consists of fine collagen fibrils and that very few proteoglycans filaments bind to them suggests that some change in the interaction of proteoglycans and collagen is responsible for the formation of long-spacing collagen. To our knowledge, this is the first ultrastructural study of the cornea from a bone marrow-transplant patient with Hurler syndrome. The structural features documented here relate to a cornea incompletely corrected by bone marrow transplantation.

Adolescent↗