Biomedical subjects

David Mann

Publications and source records attributed to David Mann.

34 records · Page 2Linked to original sources

PubMed2005

Surgical management of hydrocephalic dementia in Paget's disease of bone: the 6-year outcome of ventriculo-peritoneal shunting.

Paget's disease of bone is a chronic progressive skeletal disorder usually occurring in the long bones and skull of older adults and elderly persons. In the skull, softening of the skull base may lead to basilar impression and consequently obstruction of the cerebrospinal fluid through the basilar cisterns, resulting ventricular enlargement in association with gait difficulties, incontinence and dementia: a syndrome resembling normal pressure hydrocephalus. The optimal management of hydrocephalus associated with Paget's disease of the skull is not well documented and is still debated. We report a patient with hydrocephalic dementia linked to Paget's disease of the skull who showed marked sustained improvement in her neurological condition after ventriculo-peritoneal shunt insertion. We have now followed this patient for 6 years. Our experience supports the view that ventricular shunting is the procedure of choice for treating hydrocephalus linked to the Paget's disease of bone and is best carried out in the early stages of the illness.

Aged↗

PubMed2005

One conversion of ventricular fibrillation is adequate for implantable cardioverter-defibrillator implant: an analysis from the Low Energy Safety Study (LESS).

OBJECTIVES: The purpose of this study was to analyze defibrillation conversion data from the Low Energy Safety Study (LESS) to determine how implant criteria that use fewer inductions of ventricular fibrillation (VF) correlate with outcome and, in particular, to assess the reliability of using a single VF induction and test shock at 14 J. BACKGROUND: A safety margin of 10 J has become standard for implantation of an implantable cardioverter-defibrillator (ICD), but the specifics and rigor of the implant test sequence are not standardized. METHODS: In LESS, 611 ICD recipients completed a rigorous VF induction test scheme that began at 14 J and continued until the energy that succeeded three times without a failure was determined (DFT++). The data were analyzed to determine how well the outcome of the first 14-J shock and various other combinations of first and/or second shocks predicted a rigorous gold standard of DFT++ < or =21 J (i.e., three successes at < or =21 J). RESULTS: The positive predictive accuracy for the 91% of patients in whom the first 14-J shock succeeded was virtually identical to the positive predictive accuracy for the commonly used criteria of two successes at < or =17 J (99.1% vs 99.0%, P = .69), and slightly higher than the positive predictive accuracy for two successes at < or =21 J (98.8%, P = .51). A single success at 17 J or 21 J had a somewhat lower positive predictive accuracy of 98.2% (P = .17). Eliminating VF induction testing would have resulted in a significantly lower positive predictive accuracy of 97.1% (P = .01). CONCLUSIONS: A single conversion success at 14 J on the first VF induction provides similar positive predictive accuracy as two successes at 17 J or 21 J. Using this criterion, 91% of patients meet implant criteria with a single induction of ventricular fibrillation.

Aged↗

PubMed2005

Frontotemporal dementia.

Frontotemporal dementia (FTD) is a focal clinical syndrome characterised by profound changes in personality and social conduct and associated with circumscribed degeneration of the prefrontal and anterior temporal cortex. Onset is typically in the middle years of life and survival is about 8 years. The presence of microtubule-associated-protein-tau-based pathological features in some patients and the discovery, in some familial cases, of mutations in the tau gene links FTD to other forms of tauopathy, such as progressive supranuclear palsy and corticobasal degeneration. However, more than half of all patients with FTD, including some with a strong family history, show no apparent abnormality in the tau gene or protein, indicating pathological and aetiological heterogeneity. FTD provides a challenge both for clinical management and for theoretical understanding of its neurobiological substrate.

Behavior↗

PubMed2004

Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies.

Abnormalities in tau mRNA splicing cause frontotemporal dementia and parkinsonism linked to chromosome 17, and similar alterations are suggested in sporadic tauopathies such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). We have analyzed the expression of three-repeat (3R) and four-repeat (4R) tau isoforms in brains with familial and sporadic tauopathies. By RT-PCR analysis, decreased levels of 3R tau mRNA were detected not only in severely affected cases with progressive supranuclear palsy or corticobasal degeneration but also in cases with Alzheimer's disease or Pick's disease. Levels of 3R tau transcripts were closely correlated with levels of neurofilament transcripts. By contrast, expressions of glial fibrillary acidic protein and myelin basic protein were similar in all brains. These results suggest that decrease of 3R tau mRNA associated with loss of neuronal element may largely contribute to the increased ratio of 4R/3R tau mRNA in sporadic tauopathies.

Basic Helix-Loop-Helix Proteins↗

PubMed2004

Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease.

Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of alpha4beta2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the beta2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the alpha4 and beta2 subunits, CHRNA4 and CHRNB2 respectively, for genetic associations with late-onset AD. A significant association for disease was observed for a non-coding polymorphism in CHRNB2 (odds ratio=0.57, 95% confidence interval=0.35-0.95, P=0.024). Replication analysis was performed in two further sample sets. While these did not individually yield significant results, a significant association remained when all samples were pooled (odds ratio=0.70, 95% confidence interval=0.52-0.95, P=0.019). These data suggest that this variant warrants further examination in large case-control series.

Aged↗

PubMed2004

High-field quasiballistic transport in short carbon nanotubes.

Single walled carbon nanotubes with Pd Ohmic contacts and lengths ranging from several microns down to 10 nm are investigated by electron transport experiments and theory. The mean-free path (MFP) for acoustic phonon scattering is estimated to be l(ap) approximately 300 nm, and that for optical phonon scattering is l(op) approximately 15 nm. Transport through very short (approximately 10 nm) nanotubes is free of significant acoustic and optical phonon scattering and thus ballistic and quasiballistic at the low- and high-bias voltage limits, respectively. High currents of up to 70 microA can flow through a short nanotube. Possible mechanisms for the eventual electrical breakdown of short nanotubes at high fields are discussed. The results presented here have important implications to high performance nanotube transistors and interconnects.

Journal Article↗

PubMed2004

Evidence of a founder effect in families with frontotemporal dementia that harbor the tau +16 splice mutation.

The +16 exon 10 splice mutation of the tau gene (microtubule-associated protein tau, MAPT) has been reported in numerous families with frontotemporal dementia (FTD). To date, the majority of these families are from England and Wales in the UK, although families with this mutation have been reported from Australia and the USA. Our own analysis has identified eight families with the +16 MAPT splice mutation from around the Manchester and North Wales areas of the UK. Given the proximity of the UK families to one another it is likely that they are related and represent a single extended pedigree. In order to investigate this possibility, and the possibility that the families with this mutation from London, the USA, and Australia are related, we genotyped 11 microsatellite markers around the tau locus. In most cases (20/25, 80%), a common haplotype, approximately 3 cM in size, was identified. In the remaining cases, this haplotype appears to have been varyingly reduced in size by recombination. We demonstrate that the +16 mutation is on the H1 tau haplotype and that H1 specific polymorphisms are also shared by these families. These data provide evidence that the MAPT +16 splice mutation cases from around the world analyzed in this study are indeed related and represent a single pedigree that probably originated in the North Wales area of the UK. Furthermore, this single large pedigree may be of use in the identification of disease modifying loci in FTD.

Australia↗

PubMed2004

Alpha-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease.

The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.

Aged↗

PubMed2003

Increased expression of endoarterial vascular cell adhesion molecule-1 mRNA in an experimental model of lung transplant rejection: diagnosis by pulmonary arterial biopsy.

BACKGROUND: Early detection of rejection after lung transplantation may prevent allograft failure. This study determines if mRNA from the cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in pulmonary endovascular tissue samples could be markers of early rejection. METHODS: Single left lung transplants were performed in five dogs. Each dog was treated for 2 weeks with immunosuppression, after which rejection was allowed to occur. Percutaneous biopsies from 2- to 3-mm distal branch pulmonary arteries were obtained in each dog from the normal and the transplanted lungs at the end of immunosuppression therapy and periodically (2-4 times) for 1 to 3 weeks until euthanasia. Levels of cell adhesion molecule mRNA in the biopsy samples were quantitated by reverse-transcriptase polymerase chain reaction and normalized to beta-actin mRNA levels. RESULTS: Between three and five pulmonary endoarterial biopsy samples were obtained from each lung at each catheterization procedure. There was a significant increase in VCAM-1 mRNA levels in the biopsies of the transplanted lungs (which were undergoing rejection) compared with the native right lungs in all dogs. Progressive increases in VCAM-1 mRNA were observed with longer rejection times. VCAM-1 mRNA changes were detected earlier than histologic changes of rejection. CONCLUSIONS: In pulmonary endoarterial biopsy samples obtained in a canine lung transplant model, there was a progressive increase in VCAM-1 mRNA levels with increasing rejection. Changes in VCAM-1 mRNA were observed earlier than histologic changes of rejection. VCAM-1 quantitation by endoarterial biopsy may be useful in surveillance and early diagnosis of rejection in patients who undergo lung transplantation.

Animals↗

PubMed2003

Selective reduction of soluble tau proteins in sporadic and familial frontotemporal dementias: an international follow-up study.

Recently, biochemical criteria were proposed to complement histological criteria for the diagnosis of dementia lacking distinctive histopathology (DLDH), the most common pathological variant of frontotemporal dementias (FTDs), based on evidence of a selective reduction of soluble tau proteins in brains from a large cohort of sporadic DLDH and hereditary FTD (HDDD2 family) patients. To ensure that these findings are not unique to the populations included in the initial report, we extended the previous work by analyzing 22 additional DLDH brains from the United States and international centers. Our biochemical analyses here confirmed the previous findings by demonstrating substantial reductions in soluble brain tau in gray and white matter of 14 cases and moderate reductions in 6 cases of DLDH. We also analyzed brain samples from an additional affected HDDD2 family member, and remarkably, unlike other previously studied members of this kindred, this patient's brain contained substantial amounts of pathological or insoluble tau. These findings confirm and extend the definition of DLDH as a sporadic or familial "tau-less" tauopathy with reduced levels of soluble brain tau and no insoluble tau or fibrillary tau inclusions, and the data also underline the phenotypic heterogeneity of HDDD2, which parallels the phenotypic heterogeneity of other hereditary neurodegenerative FTD tauopathies caused by tau gene mutations.

Adult↗

PubMed2003

Tau haplotype frequency in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

It has been reported that the H1 haplotype of the tau gene, located on chromosome 17q21, is associated with progressive supranuclear palsy. Recently, it has also been claimed that the H1 haplotype could also be a risk factor for frontotemporal dementia. However, these claims are variable and the involvement of the apolipoprotein E gene as well as the H1 haplotype has been suggested. In light of this we assessed the frequency of tau gene haplotypes in 113 cases of frontotemporal lobar degeneration and 168 control samples. We found a positive association between the H1 haplotype and frontotemporal dementia, but not with any of the other disease groupings (P = 0.029, odds ratio 1.81). We did not observe any affect on age at onset and tau haplotype or apolipoprotein E alleles, nor were any deviation from control frequencies of apolipoprotein E alleles observed. These data are consistent with the hypothesis that the tau gene, or nearby gene on the H1 haplotype, is a risk factor for frontotemporal dementia.

Age of Onset↗

PubMed2002

Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions.

alpha-Synuclein is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and Hallervorden-Spatz disease, which are referred to as alpha-synucleinopathies. We have shown previously (Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., and Iwatsubo, T. (2002) Nat. Cell Biol. 4, 160-164) that alpha-synuclein deposited in synucleinopathy brains is extensively phosphorylated at Ser-129 and migrates at 15 kDa. Here we examined the biochemical characteristics of the additional, higher molecular mass species of phosphorylated alpha-synuclein-positive polypeptides that also are recovered in the Sarkosyl-insoluble fraction of synucleinopathy and migrate at about 22 and 29 kDa. These 22 and 29 kDa bands were positive for three different anti-ubiquitin antibodies and comigrated perfectly with in vitro ubiquitinated alpha-synuclein that may correspond to mono- and diubiquitinated alpha-synuclein, respectively. Furthermore, cyanogen bromide cleavage of the 22 and 29 kDa polypeptides shifted the mobility to 19 and 26 kDa, respectively, and they retained immunoreactivity for both ubiquitin and alpha-synuclein. Finally, protein sequence analysis showed that the 19 kDa band contained two amino-terminal sequences of alpha-synuclein and ubiquitin. These results strongly suggest that phosphorylated alpha-synuclein is targeted to mono- and diubiquitination in synucleinopathy brains, which may have implications for mechanisms of these diseases.

Aged↗

PubMed2002

Sporadic Pick's disease: a tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter.

Pick's disease is characterized neuropathologically by distinct tau-immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble tau proteins with predominantly three microtubule-binding repeat tau isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule-binding repeat, detected other tau lesions in Pick's disease. To better define the spectrum of tau pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the tau isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule-binding repeat pathological tau isoforms are present in gray and white matter of various brain regions. Using phosphorylation-dependent anti-tau antibodies, we show that major tau phosphoepitopes are present in sarcosyl-insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule-binding repeat tau isoforms are present in Pick bodies from selected brains. Isolated tau filaments were straight or twisted and formed by three microtubule-binding repeat or four microtubule-binding repeat tau isoforms. Major tau phosphorylation-dependent and exon 10-specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule-binding repeat tau pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.

Aged↗

PubMed2002

Osteoporosis risks. A comparative study of Asian Australian and Caucasian Australian women.

OBJECTIVE: To describe the self reported level of osteoporosis knowledge, attitudes and preventive activities, including dietary calcium intake of Asian and Caucasian women. METHOD: Self administered questionnaires in English and Chinese including a food frequency survey were posted to potential respondents that were recruited via general practices, community newsletters and notices. RESULTS: Asian women had less osteoporosis knowledge and lower calcium intake (mean 793 +/- 49 mg/day standard error of the mean) than Caucasian women (1298 +/- 56 mg/day). Postmenopausal Asian women were at greater risk of being below the recommended daily intake (73%) than Caucasian women (31%). CONCLUSION: Osteoporosis knowledge and preventive activities among Asian and Caucasian women could be better. Higher dietary or supplementary calcium intake should be considered.

Adult↗

PubMed1998

An exploratory study of the relationship between face recognition memory and the volume of medial temporal lobe structures in healthy young males.

A rigorous new methodology was applied to the study of structure function relationships in the living human brain. Face recognition memory (FRM) and other cognitive measures were made in 29 healthy young male subjects (mean age = 21.7 years) and related to volumetric measurements of their cerebral hemispheres and of structures in their medial temporal lobes, obtained using the Cavalieri method in combination with high resolution Magnetic Resonance Imaging (MRI. Greatest proportional variability in volumes was found for the lateral ventricles (57%) for the cerebral hemispheres (8%) in the mean volumes of the hippocampus, parahippocampal gyrus, amygdala, caudate nucleus, temporal pole and temporal lobe on the right and left sides of the brain. The volumes of the right and left parahippocampal gyrus, temporal pole, temporal lobe, and left hippocampus were, prior to application of the Bonferroni correction to take account of 12 multiple comparisons, significantly correlated with the volume of the corresponding hemisphere(p < 0.05). The volumes of all structures were highly correlated (p < 0.0002 for all comparisons) between the two cerebral hemispheres. There were no positive relationships between structure volumes and FRM score. However, the volume of the right amygdala was, prior to application of the Bonferroni correction to take account of 38~multiple comparisons, found to be significantly smaller in the five most consistent high scorers compared to the five most consistent low scorers (t = 2.77,p = 0.025). The implications for possible relationships between healthy medial temporal lobe structures and memory are discussed.

Journal Article↗

PubMedDate not supplied

Rapid progression of scoliosis following insertion of intrathecal baclofen pump.

Placement of an intrathecal baclofen pump is a common treatment of spasticity in cerebral palsy patients. Though effective, the hardware is prone to malfunction, and multiple revisions are often necessary. Additional complications have also been described, including infection and drug toxicity or withdrawal. The authors report another complication of intrathecal baclofen therapy: accelerated progression of scoliosis after pump insertion. A retrospective chart review was performed on four patients who showed accelerated scoliotic progression after intrathecal baclofen pump insertion for treatment of spasticity. Cobb angles were measured from preoperative and postoperative radiographs to determine the rate of scoliotic degeneration both before and after pump insertion. Although there may not be a direct correlation between intrathecal baclofen and scoliosis, the authors consider the issue important enough to warrant discussion with any patient considering intrathecal baclofen.

Adult↗