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P Blumbergs

Publications and source records attributed to P Blumbergs.

At least 19 recordsLinked to original sources
PubMed2005

Topography of c-fos immunoreactivity in an ovine head impact model.

Cortical neuronal and glial c-fos immunoreactivity has been demonstrated in experimental and human brain injury. c-fos is one of the immediate early genes important in signal transduction linking environmental stimuli to the cellular genome. c-fos immunoreactivity was semi-quantitated in a head impact sheep model using a grid system applied to standard coronal brain sections obtained from 12 impacted and 4 control sheep. Substantial glial and neuronal c-fos immunoreactivity was present in the pericontusional (penumbra) region, but was absent or minimal in the core of the contusion. Apart from these focal changes, c-fos immunoreactivity was diffusely distributed, with greater involvement in the cerebrum on the side of impact. In the cerebellum, Bergmann glia showed prominent c-fos immunoreactivity, while Purkinje cells were consistently immunonegative. c-fos immunoreactivity varied in different regions of the brain (focal and diffuse patterns) in this ovine head impact model.

Animals↗
PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗
PubMed2001

Visual field loss associated with vigabatrin: pathological correlations.

Pathological changes are reported in the anterior visual pathways of a 41 year old man with complex partial seizures treated with vigabatrin who developed bilateral visual field constriction. There was peripheral retinal atrophy with loss of ganglion cells and loss of nerve fibres in the optic nerves, chiasm, and tracts. No evidence of intramyelinic oedema was seen. These findings suggest that the primary site of injury lies within the ganglion cells in the retina. The degree of atrophy seen would suggest that the visual field loss is irreversible.

Adult↗
PubMed2000

Upregulation of amyloid precursor protein and its mRNA in an experimental model of paediatric head injury.

Amyloid precursor protein (APP), a membrane spanning glycoprotein which plays an important role in neuronal growth and synaptic plasticity, is increased after traumatic brain injury (TBI) and has been used as a sensitive marker of neuronal damage in an adult sheep head impact model. We hypothesised that APP expression would similarly be increased in lambs, suggesting that in the immature injured brain APP is also upregulated as an acute phase response to trauma. Ten anaesthetised and ventilated 4-5 week old Merino lambs sustained a left temporal head impact from a humane stunner. At 2 h after impact, there was widespread and intense neuronal cell body APP immunoreactivity which was more widely distributed than axonal APP. APP messenger RNA (mRNA) expression was also markedly increased with a distribution similar to that of APP antigen. These results demonstrate that APP antigen and mRNA are sensitive early indicators of TBI in paediatric cases.

Amyloid beta-Protein Precursor↗
PubMed1998

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice.

Previously we described activating mutations of hbetac, the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the hbetacFIDelta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in hbetac may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic hbetac activation has the potential to contribute to pathological events in the central nervous system.

Animals↗
PubMed1998

Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model.

Amyloid precursor protein (APP) has been shown to accumulate in traumatically injured axons as early as 1 hour after injury. This accumulation may be due to interruption of fast axoplasmic transport and/or upregulation of APP synthesis. The aim of this study was to examine the neuronal cell body response to head impact using APP immunostaining in a focal non-missile head impact model. Ten anaesthetised and ventilated 2 year old Merino ewes were subjected to graded impact in the left temporal region by captive bolt. 2 hours after impact the brain was perfused fixed with formaldehyde. The tissue was mounted in paraffin, sectioned and stained with a monoclonal antibody to APP and standard H&E stain. APP positivity was semi-quantitated using a modification of our previously described sector scoring system [1]. Widespread neuronal APP positivity was found in the cerebral hemispheres and brain stem distant from the site of focal injury in all 10 animals. The most prominent APP positivity was found in the nerve cell bodies of the impacted left cerebral hemisphere. APP positive neurons were also found within regions which were structurally normal when stained with H&E. These results demonstrate diffuse neuronal perikaryon APP immunoreactivity following a focal head impact injury. The expression of APP within the neuronal cell body may be due to upregulation of APP synthesis or alterations in the availability of epitopes of APP. Further studies are in progress to address these hypotheses.

Amyloid beta-Protein Precursor↗
PubMed1995

A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.

Nemaline myopathies are diseases characterized by the presence in muscle fibres of pathognomonic rod bodies. These are composed largely of alpha-actinin and actin. We have identified a missense mutation in the alpha-tropomyosin gene, TPM3, which segregates completely with the disease in a family whose autosomal dominant nemaline myopathy we had previously localized to chromosome 1p13-q25. The mutation substitutes an arginine residue for a highly conserved methionine in a putative actin-binding site near the N terminus of the alpha-tropomyosin. The mutation may strengthen tropomyosin - actin binding, leading to rod body formation, by adding a further basic residue to the postulated actin-binding motif.

Amino Acid Sequence↗
PubMed1994

Inclusion body myositis in association with rheumatoid arthritis.

We describe 2 patients with rheumatoid arthritis (RA) and inclusion body myositis (IBM). Examination and laboratory tests including muscle biopsy with frozen section and electron microscopy were performed. Both patients fulfilled diagnostic criteria for IBM, which is increasingly recognized in association with autoimmune disease. A high index of suspicion and early thorough investigation are required to diagnose IBM in patients with RA.

Aged↗
PubMed1993

A dominant hereditary ataxia resembling Machado-Joseph disease in Arnhem Land, Australia.

A dominant ataxia among four families of the Arnhem Land Aboriginal people of Northern Australia has many clinical features in common with Machado-Joseph disease. Neuropathology on one case showed multiple system involvement, with sparing of the inferior olives and cerebellar cortex, consistent with Machado-Joseph disease. Portuguese ancestry is possible, although not proven.

Adult↗
PubMed1992

Enterogenous cyst of the cervical spinal canal.

A case of an enterogenous cyst of the cervical spinal canal in an 18 year old man is presented, high-lighting the radiological findings. A brief overview is given of these rare cysts, together with their clinical and radiological features and associations.

Adolescent↗
PubMed1992

Amygdalo-hippocampectomy for pathological aggression.

Two patients are reported, one with severe brain damage and epilepsy, and the other with limbic epilepsy, who were treated with unilateral microsurgical amygdalo-hippocampectomy for the control of rage and aggression. Both had significant improvement in their aggressiveness, and the second patient also improved in the frequency of his seizures and psychotic episodes. The significance of these observations for our understanding of the morphophysiological basis of rage and aggression is discussed.

Adult↗
PubMed1992

Cholinesterase studies with (R) (+)- and (S)(-)-5-(1,3,3-trimethylindolinyl)-N-(1-phenylethyl)carbamate.

A limited number of carbamates have been found useful for treatment of cholinergic symptoms with pyridostigmine and physostigmine being the main focus. In recent years 5-(1,3,3-trimethylindolinyl)N,N-dimethylcarbamate (I) has received considerable attention in the Chinese literature for a similar role. We report on the first synthesis of stereoisomers of an analog of (I). The isomers prepared were (R)(+)-5-(1,3,3-trimethylindolinyl)-N-(1-phenylethyl)carbamate (II) and (S)(-)-5-(1,3,3-trimethylindolinyl)-N-(1-phenylethyl)carbamate (III). The pKa value for each isomer was 6.8. Eel acetylcholinesterase inhibition studies were carried out at 25.0 degrees C over the pH range of 6.0 to 9.0. They reflect the first pH profiles using enantiomorphs of a cholinesterase inhibitor. The inhibition potencies for (II) and (III) over the range examined were similar. At pH 7.60 the ki for II = 7.38 x 10(3) M-1 min-1 (SD = 398) and for (III) the ki = 6.67 x 10(3) M-1 min-1 (SD = 355). In accord with the findings of Wilson and Bergmann20 on physostigmine our results indicate that the protonated form of (II) and (III) is the more potent inhibitor.

Acetylcholinesterase↗
PubMed1991

Iatrogenic spinal subdural haematoma.

Spinal subdural haematoma is a rare condition, usually seen in association with lumbar puncture or a bleeding disorder. It carries a high morbidity and mortality, and successful treatment requires prompt surgical intervention. We present a case of mixed spinal subarachnoid and subdural haemorrhage complicating failed spinal anaesthesia combined with anti-coagulation in an elderly woman, together with a review of the literature.

Aged↗
PubMed1991

Anticholinesterase activity of potential therapeutic 5-(1,3,3-trimethylindolinyl) carbamates.

Six N-alkyl and N-aryl 5-(1,3,3-trimethylindolinyl) carbamates were synthesized and studied for their structure-activity relationships in inhibiting eel acetylcholinesterase (AChE). The carbamates were 5-(1,3,3-trimethylindolinyl)N,N-dimethylcarbamate (Cui Xing Ning) (I), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-ethylcarbamate (III), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-heptylcarbamate (V), and 5-(1,3,3-trimethylindolinyl)N-(3-chlorophenyl)carbamate (VI). The inhibition studies were carried out at 25.0 degrees C at pH 7.60. The rank order of the ki values for eel AChE inhibition is II > V > I > III > VI > IV. Compound II has a greater affinity for the enzyme than any irreversible inhibitor cited in the literature (Kd = 7.14 x 10(-8) M). Our findings should aid in the application of these carbamates (1) for counteracting the cholinergic problems associated with various diseases, and (2) for developing potential pretreatment compounds for organophosphate poisoning.

Acetylcholinesterase↗
PubMed1990

Malignant astrocytoma in South Australia: treatment and case survival.

Kernohan grade III and IV astrocytomas are usually fetal and in the past have had a case survival rate of only about 10% two years from diagnosis. Data on 285 cases registered at the Royal Adelaide Hospital in 1977-1986 showed a median survival of approximately six months. The survival rate was 25% at one year and 15% at two years. Survival reduced markedly with increase in age at diagnosis from a two-year rate of 53% for patients under 40 years of age to 5% for patients aged 70 years or more. This may have been due in part to the more frequent treatment of younger patients by decompression and radiotherapy. Apart from age and treatment mode, factors related to extended survival included a longer duration of symptoms before diagnosis and location of the tumour in the frontal lobes. Notwithstanding prospects for an increase in short-term survival from the use of radiotherapy as an adjunct to surgery, long-term outcomes for these neoplasms are still very poor.

Adult↗
PubMed1989

Fatal rhabdomyolysis and renal failure associated with hand, foot and mouth disease.

Fatal severe rhabdomyolysis and anuric renal failure developed in a young man who had contracted hand, foot and mouth disease during an epidemic of this disease. Viral studies implicated coxsackievirus A16 as the infecting agent. This appears to be the first reported case of rhabdomyolysis that was associated with hand, foot and mouth disease and infection with coxsackievirus A16.

Adult↗
PubMed1989

Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials.

A series of 2-substituted analogues of the exceptional drug 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline (I) were prepared and evaluated for both suppressive and prophylactic antimalarial activity. The preparation of analogues of compound I was of interest due to the high level of both blood and tissue schizonticidal activity demonstrated by this compound. One analogue, 8a, was found to be both more active and less toxic than the parent compound I. In addition, three analogues of example 8a were prepared. Although two of the three analogues showed significant antimalarial activity, both were inferior to compound 8a.

Aminoquinolines↗