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C Schultz

Publications and source records attributed to C Schultz.

139 records · Page 8Linked to original sources
PubMedDate not supplied

Age-related progression of tau pathology in brains of baboons.

Recently, cytoskeletal changes associated with abnormally phosphorylated tau protein were demonstrated in neurons and glial cells of two aged baboons (Papio). The present study examines the effects of age on the development of tau pathology in baboons. Brains of 50 baboons ranging in age from 1 to 30 years were categorized into four age groups: Group I: 1-10 years [n = 9], group II: 11-20 years [n = 13], group III: 21-25 years [n = 17], group IV: 26-30 years [n = 11]). Whole hemisphere sections (100 microm) were examined using phosphorylation-dependent anti-tau antibodies. Cytoskeletal changes were completely absent in animals of group I. In group II four animals (31%) exhibited cytoskeletal changes which were rated as mild or moderate. In group III abnormal tau was found in 12 brains (71%) ranging in severity from mild to severe. Finally, in group IV 10 out of 11 animals (91%) exhibited some degree of tau pathology which was rated as severe in 4 animals (36%). A statistically significant relationship was found between advancing age and progression of tau pathology in baboons. In conclusion, the present findings underline the value of the baboon as a potential nonhuman primate model for age-related tau pathology afflicting the human brain.

Aging↗
PubMedDate not supplied

Expression of stress proteins alpha B-crystallin, ubiquitin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys.

Ubiquitin and alpha B-crystallin belong to a class of proteins which are overexpressed in a variety of human neuropathological conditions associated with increased cellular stress. In this study we have examined the brains of aged rhesus monkeys (Macaca mulatta; n = 10, mean age: 29.7 years) using antibodies against the stress proteins ubiquitin, alpha B-crystallin, and heat shock protein 27 (hsp27). Here, we demonstrate an increased expression of ubiquitin, alpha B-crystallin, and hsp27 in spheroid bodies predominantly localized in the globus pallidus and pars reticulata of the substantia nigra. A portion of the pallido-nigral spheroids also contained ferric iron as highlighted by Perls' staining. On the basis of these findings we advance the hypothesis that expression of ubiquitin, alpha B-crystallin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys represents a stress response possibly related to increased iron-mediated oxidative stress.

Aging↗
PubMedDate not supplied

Parkinson's disease: the thalamic components of the limbic loop are severely impaired by alpha-synuclein immunopositive inclusion body pathology.

The Parkinson's disease (PD)-related inclusion body pathology comprises Lewy bodies (LBs) as well as Lewy neurites (LNs). The distribution and severity of this pathology were investigated in the thalamus of 12 autopsy cases with clinically diagnosed and neuropathologically confirmed PD. The LBs and LNs were visualized by immunoreactions against the protein alpha-synuclein. In the human thalamus during PD, a specific and highly stereotypical distribution pattern of LBs and LNs evolves. As in cortical and other subcortical regions, the components of human thalamus assigned to the limbic loop bear the brunt of the PD-related pathology. In contrast, the thalamic components integrated into the striatal and cerebellar loops as well as the primary sensory nuclei of the thalamus show at best a mildly developed pathology. Damage to the thalamic components of the limbic loop nuclei may contribute not only to the cognitive, emotional, and autonomic symptoms of PD but to the somatomotor and oculomotor dysfunctions as well.

Aged↗
PubMedDate not supplied

Assessment of the pathological stages of Alzheimer's disease in thin paraffin sections: a comparative study.

The staging method proposed by Braak and Braak allows the objective and reliable assessment of Alzheimer-related neurofibrillary pathology. Originally the method was designed for 100-microm thick sections. However, the use of thick sections proved to present difficulties in a routine neuropathology laboratory. In order to adapt the staging method for thin paraffin-embedded sections, we performed an inter- and intrarater study analysing the reliability of the staging method in thin sections. Statistical analysis of the data provided by six independent examiners in two rating sessions reveal kappa values of 0.6-0.8 for both the interrater and the intrarater reliability. The average rate of mistake of the examiners was rarely bigger than a half stage. We conclude that the adapted staging method in thin sections is strongly reliable and we recommend it for staging purposes in institutions where the preparation of thick sections would be difficult.

Alzheimer Disease↗
PubMedDate not supplied

Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study.

The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.

Aged↗
PubMedDate not supplied

The progression of Alzheimer's disease from limbic regions to the neocortex: clinical, radiological and pathological relationships.

Alzheimer's disease (AD) is characterised by the gradual accumulation of neurofibrillary pathology in selected regions of the brain. Earlier studies indicate that the accumulation of neurofibrillary tangles is associated both with decline in patient's cognitive performance as well as with medial temporal lobe atrophy on CT scans. There are also indications that progression through the pathological stages of AD is associated with decline in cognitive functions. The results of this study indicate that progression of disease, especially beyond the boundaries of the limbic regions, is associated with marked decline in the cognitive performance of patients suffering from AD. However the clinical manifestations of early pathological stages are not so well defined. We also found that the atrophy of the medial temporal lobe on CT scans is related to the progression of pathology. Atrophy is most apparent when the disease reaches its isocortical stages and is not marked in the limbic stages of the disease. The additive effect of pathologies co-existing with AD is apparent in reduced cognitive scores, while the atrophy of limbic structures, as measured on CT scans, seems to be mainly attributable to AD-related pathology.

Aged↗
PubMedDate not supplied

Staging of Alzheimer-type pathology: an interrater-intrarater study.

The staging method proposed by Braak and Braak is based on the sequential accumulation of neurofibrillary pathology in the cerebral cortex. Unlike the currently used diagnostic criteria for Alzheimer's disease (AD) it does not take into consideration the age of the patients and whether they were demented or not for the establishment of the pathological stage of the disease. To examine the interobserver reliability of the method we performed an inter- and intrarater study using the Braak staging method in 41 brains. The agreement between the examiners and between the diagnoses of the same examiner at different times was almost perfect, the kappa statistics reaching values above 0.90. These findings indicate that the staging, relying on the differential distribution of neuritic pathology in the brain in AD, is a reliable and reproducible method for the description of AD-related pathology. This makes it suitable for brain-banking and research purposes.

Aged↗
PubMedDate not supplied

Current care of hepatitis C-positive patients by primary care physicians in an integrated delivery system.

BACKGROUND: Infection with the hepatitis C virus (HCV) is an emerging health problem in the United States. Management of this condition in asymptomatic patients remains controversial. METHODS: A questionnaire was mailed in November 1997 to all primary care physicians caring for adults (internists and family physicians) in an integrated health delivery system regarding the current approach to screening, diagnosis, and management of HCV infection. Charts of patients whose tests were positive for HCV were audited in selected practice sites to document care received by those patients. RESULTS: Most physicians (70%) reported ordering alanine aminotransferase (ALT) measurements to screen for HCV infection as part of a complete checkup. Each physician diagnosed an average of 3.1 new cases of HCV infection per year. Patients received widely divergent advice regarding prognosis, precautions to prevent transmission, and treatment. More than one half of the physicians advised their patients that the condition was serious (68%) and to abstain from alcohol (56%) and use condoms in monogamous relationships (62%). In caring for HCV-positive patients, more than three quarters of physicians reported recommending a liver biopsy to patients who had elevated ALT levels, and observing clinically, without liver biopsy, those patients who had normal ALT levels. A chart audit, however, showed less-aggressive intervention. Approximately one third of HCV-positive patients with elevated ALT levels had been seen by a gastroenterologist and had had a liver biopsy. Physicians in practice longer were less likely to recommend treatment with interferon-alpha. Of those patients whose physicians reported they would recommend biopsy and treatment with interferon-alpha, only 36% had a documented liver biopsy in their charts, and 29% had documented interferon-alpha treatment. Only 1.6% and 3.0% of patients, respectively, had received the recommended hepatitis A and hepatitis B vaccines. CONCLUSIONS: Approaches to screening, diagnosis, and management of HCV infection by primary care physicians vary greatly. There appears to be a considerable population of patients in primary care settings who continue to receive conservative management of asymptomatic HCV infection.

Adult↗
PubMedDate not supplied

UV light-induced autofluorescence of full-length Abeta-protein deposits in the human brain.

The formation of amyloid plaques is a hallmark of Alzheimer's disease (AD). Amyloid plaques and vascular amyloid deposits in cerebral amyloid angiopathy (CAA) consist of the beta-amyloid protein (Abeta) in association with other proteins. These Abeta-deposits can be visualized by thioflavin S, Congo red staining, silver staining methods and immunohistochemistry. Senile plaques also have been shown to exhibit blue autofluorescence. Here we report that UV light-induced autofluorescence is restricted to full-length Abeta-containing amyloid plaques and is also seen in blood vessels affected by CAA. Different types of samples from AD and control cortices were examined: native samples, formalin-fixed paraffin and polyethylene glycol-embedded tissue sections. These samples were viewed with a fluorescence microscope under UV light excitation (360 - 370 nm). By emitting blue fluorescence (>420 nm), amyloid plaques and blood vessels affected by CAA were detected in AD and CAA samples. Combination with immunofluorescence against anti-Abeta1-42, anti-Abeta17-24, and anti-Abeta8-17 demonstrated co-localization of the autofluorescent deposits with full-length Abeta containing Abeta-deposits. N-terminal truncated Abeta-deposits, such as the fleecy amyloid, do not exhibit autofluorescence. In doing so, Abeta-autofluorescence is a suitable method for screening native tissue samples for full-length Abeta-deposits. In contradistinction to conventional and immunohistochemical procedures, detection of plaques and CAA by autofluorescence enables the recognition of full-length Abeta-deposits in the human brain without any chemical interaction whatsoever on the part of Abeta.

Aged↗
PubMedDate not supplied

The dying person.

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Attitude to Death↗
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Grieving children.

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Adolescent↗