Cortical Lewy body pathology in the diagnosis of dementia.

Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are distinguishable clinically but often not neuropathologically. This study aims to test whether the distribution of cortical Lewy bodies differs in these clinicopathological groups and to develop diagnostic protocols for their differentiation. Brains were obtained at autopsy from cases recruited from prospective clinical studies of dementia or movement disorders.

Interleukin-1beta but not tumor necrosis factor is involved in West Nile virus-induced Langerhans cell migration from the skin in C57BL/6 mice.

Langerhans cells are bone marrow-derived epidermal dendritic cells. They migrate out of the epidermis into the lymphatics and travel to the draining lymph nodes where they are responsible for the activation of T cells in the primary immune response. Tumor necrosis factor and interleukin-1beta, have previously been shown to be responsible for Langerhans cell migration in response to contact sensitizers in BALB/C mice; however, which cytokines are responsible for mediating Langerhans cell migration in response to a replicating cutaneously acquired virus such as the West Nile Virus, are not known.

Alzheimer's disease: its diagnosis and pathogenesis.

A hypothesis has been presented that links many of the identified and putative risk factors for AD and suggests a mechanism for their action. Crawford (1996, 1998) proposes an association between AD and cerebral blood flow (CBF) by citing evidence that many of the factors that are linked with an increased risk of AD also decrease CBF (e.g.

Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin.

The induction of epidermal immunity depends on activation of local dendritic cells (DC), Langerhans cells (LC), to migrate from the skin to local lymph nodes and mature into potent immunostimulatory cells. We have previously shown that progressor skin tumors, which evade immunological destruction, prevent contact sensitizer-induced LC migration from the skin to draining lymph nodes. In contrast, regressor tumors, which evoke protective immunity, did not inhibit DC mobilization.

Relationship between DNA fragmentation, morphological changes and neuronal loss in Alzheimer's disease and dementia with Lewy bodies.

This aim of the present study was to identify whether apoptotic features relate to the degree of cortical neuronal loss in cases with variable cortical degeneration. Neuronal apoptosis was assessed using histochemical and morphological criteria in cases with Alzheimer's disease (AD, n=7) or Lewy bodies (n= 11) compared with controls (n=11). AD cases had both significant plaque and tangle formation but no Lewy bodies, while cases with Lewy bodies had significant plaque formation but no tangles.

Effects of low-dose ultraviolet radiation on in vivo human cutaneous recall responses.

Relatively few studies have examined the effects of low-dose ultraviolet (UV) radiation on in vivo human cutaneous immunity, or the ability of sunscreens to prevent UV-induced immunosuppression. We have studied the effects of solar-simulated UV radiation on nickel contact hypersensitivity (CHS) in nickel-allergic volunteers, and on delayed type hypersensitivity responses in Mantoux-positive volunteers. Nickel CHS and Mantoux responses were significantly suppressed by acute, suberythemal UV exposures equivalent to less than 8 min summer sunlight.

Corticobasal syndrome with tau pathology.

Six cases with a clinical corticobasal syndrome (progressive asymmetric apraxia and parkinsonism unresponsive to levodopa) and tau pathology were selected from 97 brain donors with parkinsonism. Postmortem volumetric measures of regional brain atrophy (compared with age/sex-matched controls) were correlated with clinical features and the degree of underlying cortical and subcortical histopathology. At death, no significant asymmetry of pathology was detected.

Infiltration by inflammatory cells required for solar-simulated ultraviolet radiation enhancement of skin tumor growth.

In this study we compared the effects of subinflammatory and inflammatory doses of solar-simulated ultraviolet (UV) radiation on enhancement of skin tumor growth, sensitization to haptens and cellular changes within the epidermis of C3H/HeN mice. Tumors transplanted into mice 3 days after exposure to inflammatory, but not subinflammatory, doses of UV radiation had a higher growth rate than those tumors inoculated into unirradiated control mice. Both doses of UV radiation suppressed the induction of contact hypersensitivity and induced tolerance when hapten was painted onto the skin 3 days after irradiation.

Lesion of thalamic centromedian--parafascicular complex after chronic deep brain stimulation.

A patient with PD who exhibited disabling tremor and prominent dyskinesia underwent deep brain stimulation (DBS) of the left thalamic ventral intermediate nucleus. The electrode migrated and was replaced but with suboptimal clinical response. Two years later, postmortem analysis found the second electrode tip had entered the thalamic centromedian-parafascicular complex.

Parkinson's disease with late Pick's dementia.

We report a case in which typical clinical features of idiopathic Parkinson's disease existed for seven years prior to the development of significant behavioral and cognitive changes and severe dementia. The patient presented with right-sided resting tremor, bradykinesia, and rigidity, which were highly responsive to levodopa. Serial neuropsychological evaluation revealed no evidence of dementia until late in the disease.

Cortical degeneration associated with phonologic and semantic language impairments in AD.

Objective: To compare the pattern of cortical degeneration associated with different language deficits in cases of AD.

Methods: Cases for detailed neuropathologic analysis (Patients 1 and 2) were selected because of their detailed clinical and neuropsychological assessments of language dysfunction in AD. Patient 1 had severe phonologic impairment with relatively preserved semantic aspects of language.

Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation.

We describe an Australian family of Greek origin with a parkinsonian syndrome and an Ala53Thr alpha-synuclein gene mutation. Five of 9 siblings were affected, the average age of onset was 45 years, and the initial symptoms were variable, including resting tremor, bradykinesia, and gait disturbance, as previously described in families with the same point mutation. Affected family members responded well to levodopa, developed progressive cognitive impairment, and had a disease duration of 5 to 16 years.

Severe anterograde amnesia with extensive hippocampal degeneration in a case of rapidly progressive frontotemporal dementia.

Frontotemporal dementia (FTD) is usually characterized as a spectrum of relatively slowly progressive disorders with largely focal frontal or temporal presentations. The development of clinical and research criteria for discriminating FTD from Alzheimer's disease has relied, in part, on the relative preservation of episodic memory in FTD. We present a patient with FTD who, in addition to the more typical behavioural and language deficits, had a profound anterograde amnesia at the time of diagnosis.

Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells.

There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naïve recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes.

Neurofilament-immunoreactive neurons are not selectively vulnerable in Alzheimer's disease.

Abnormal neurofilament protein distribution and phosphorylation contributes to the cytoskeletal pathology of Alzheimer's disease. Anatomical studies suggest that cortical neurons immunoreactive for nonphosphorylated 200-kDa neurofilament are most vulnerable. We repeated these studies in formalin-fixed temporal lobe tissue from five Alzheimer's disease cases with tissue volume loss compared to five controls without tissue loss.

Mitochondrial ultrastructure and density in a primate model of persistent tardive dyskinesia.

The use of neuroleptic drugs to treat schizophrenia is almost invariably associated with extrapyramidal movement disorders. One of these disorders, tardive dyskinesia (TD), can persist long after neuroleptic withdrawal suggesting that permanent neurological damage is produced. However, there appears to be no convincing pathology of TD and its pathogenesis remains unknown.

Community study of people who live in squalor.

Background: The reasons why people live in squalor have been the subject of much debate but little systematic research other than reports of case series from secondary health-care services. We did a study in the community using standardised instruments to investigate the relation between squalor and mental and physical disorders.

Methods: We did a cross-sectional study of the clients of a local-authority special cleaning service.

A review of the neuropathology of schizophrenia.

1. Research on the structural basis for schizophrenia was considered a graveyard for neuropathologists, largely because its aetiology has remained obscure. However, there have been several recent major reviews and studies in leading journals on the neuropathology of schizophrenia highlighting the alterations found in the brains of schizophrenic patients.

Anti-inflammatory drugs protect against Alzheimer disease at low doses.

Context: Anti-inflammatory medications have an inverse association with Alzheimer disease (AD).

Objectives: To examine at what doses this anti-inflammatory drug effect occurs and whether other medications and/or International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses affect the association.

Design: Subjects 75 years and older from a random population sample were classified by consensus using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses.

Idiopathic generalized epilepsy: lack of significant microdysgenesis.

Background: The idiopathic generalized epilepsies (IGE) are classically regarded as due to a functional abnormality. However, microscopic microdysgenetic changes have been reported in the majority of cases by one group.

Objective: To independently evaluate the microscopic microdysgenetic changes in a controlled, blinded study.

Enhanced tumor growth in UV-irradiated skin is associated with an influx of inflammatory cells into the epidermis.

UV radiation causes a number of cellular changes within the skin which play a role in tumor outgrowth, including immunosuppression and production of growth-enhancing cytokines. Both of these enable tumors to grow but their relative importance in carcinogenesis is poorly defined. In this study, C3H/HeN mice were exposed to a single inflammatory dose of 410 mJ/cm(2) UVB radiation (plus 100 mJ/cm(2) UVA radiation) followed by the inoculation of a regressor squamous cell carcinoma into or the painting of oxazolone onto the treated skin.

Cytokine profiles in spontaneously regressing basal cell carcinomas.

Background: Basal cell carcinomas (BCCs) can cause considerable morbidity due to their ability to enlarge progressively and to destroy underlying tissues. However, some BCCs may undergo spontaneous regression in the absence of therapy capable of inducing antineoplastic effects. Histological criteria for this process have been described, and previous studies have suggested that it may be mediated by infiltrating activated CD4-positive T cells.

Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson's disease: clinical and therapeutic implications.

Whilst many reports mention neurofibrillary tangle pathology in the thalamus in progressive supranuclear palsy, there has been little detailed regional analysis of the distribution and density of thalamic pathology in this disease or in other parkinsonian syndromes. The caudal intralaminar thalamic nuclei are the major thalamic regulators of the caudate nucleus and putamen, areas known to be dysfunctional in progressive supranuclear palsy and Parkinson's disease. We investigated whether these thalamic nuclei degenerate in patients with these disorders compared with age-matched, neurologically normal controls.

Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease.

Background: There has been no analysis of brain tissue from longitudinally observed, cognitively tested patients to validate whether anti-inflammatory medications protect against the pathological changes of Alzheimer disease.

Objective: To investigate the role of anti-inflammatory medications in alleviating the pathological features of Alzheimer disease.

Design And Main Outcome Measures: A 5-year postmortem tissue collection was performed after a case-control study of Alzheimer disease (approximately 90 [30%] of patients died during follow-up, of whom consent for autopsy was obtained in 44 [50%]).

Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies.

Background: There have been no previous studies on the role of inflammation in the brain for the second most common dementing disorder, dementia with Lewy bodies.

Objective: To investigate the degree of cortical inflammation in dementia with Lewy bodies (DLB) compared with Alzheimer disease (AD) and control brains.

Design And Main Outcome Measures: Post-mortem tissue collection from a brain donor program using standardized diagnostic criteria.