background A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. methods We received clinical specimens from patients in six countries and tested them, using virus isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. results No classic respiratory or bacterial respiratory pathogen was consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted microscopically in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination of cultures revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription–polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point source outbreak. Indirect fluorescent antibody tests and enzyme-linked immunosorbent assays made with the new coronavirus isolate have been used to demonstrate a virus-specific serologic response. Preliminary studies suggest that this virus may never before have infected the U.S. population. conclusions A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. The name Urbani SARS-associated coronavirus is proposed for the virus.

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A novel coronavirus associated with severe acute respiratory syndrome.

1. The association between plaque counts in sections of cerebral cortex and measures of intellectual and personality functioning undertaken in elderly subjects during life has been studied.

2. There was no evidence that degenerative changes had contributed significantly to the causation of illness in patients with "functional" psychiatric disorders or delirious states.

3. There is a highly significant correlation between mean plaque counts and scores for dementia and performance in psychological tests. The findings suggest that psychological and pathological indices are closely related to one another, possibly through their common association with the underlying degenerative process in the brain.

4. Among severely demented subjects and those diagnosed clinically as "senile dements", correlations between psychological and pathological measures decline sharply. However, pathological differences between normal, mildly demented, and severely demented subjects appear to be of a quantitative nature. The possibility that there are qualitative differences in this group, inaccessible to present methods of examination, cannot be excluded.

The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70124-8.pdf

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

http://lib.ajaums.ac.ir/booklist/archives%20of%20neurology_24%20Jan-2_17.pdf

The cardiovascular health study: Design and rationale

A new variant of Creutzfeldt-Jakob disease in the UK

Ultrastructural studies in alzheimer's presenile dementia.

With a technique of preselecting the mitotic cell in the living state for subsequent electron microscopy, it has been possible to examine the ultrastructure of the various stages of mitosis with greater precision than has been reported previously. The early dissolution of the nuclear envelope has been found to be preceded by a marked undulation of this structure within the nuclear "hof." This undulation appears to be intimately related to the spindle-forming activity of the centriole at this time. Marked pericentriolar osmiophilia and extensive arrays of vesicles are also prominent at this stage, the former continuing into anaphase. Progression of the cell through prophase is accompanied by a disappearance of these vesicles. A complex that first makes its appearance in prophase but becomes most prominent in metaphase is a partially membrane-bounded cluster of dense osmiophilic bodies. These clusters which have a circumferential distribution in the mitotic cell are shown to be derived from multivesicular bodies and are acid phosphatase-positive. The precise selection of cells during the various stages of anaphase has made it possible to follow chronologically the morphological features of the initiation of nuclear membrane reformation. The nuclear membrane appears to be derived from polar aggregates of endoplasmic reticulum, and the process begins less than 2 minutes after the onset of karyokinesis. While formation of the nuclear envelope is initiated on the polar aspects of the chromatin mass, envelope elements appear on the equatorial aspect long before the polar elements fuse. Apparently interfering with this fusion are continuous spindle tubules which traverse the chromatin mass in striking density at characteristic points. Several cortical changes, also most pronounced in anaphase, have been described, as has the kinetochore which is seen to good advantage only in this stage. The Golgi complex has been found to disappear both morphologically and histochemically during mitosis and to reappear rapidly in telophase. Evidence is presented which implicates the continuous spindle tubules in certain phases of chromosome movement.

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The ultrastructure of a mammalian cell during the mitotic cycle

We have compared the retrograde axonal transport of horseradish peroxidase (HRP), to the retrograde transport of HRP conjugated with wheat germ agglutinin (WGA). Morphometric studies have shown that WGA-HRP conjugates were 40 times more sensitive than free HRP, in the tracing of retrograde connections from the rat submandibular gland to the superior cervical ganglion. Also, WGA-HRP was more sensitive than free HRP in the tracing of retrograde connections from the rat tongue to the hypoglossal nucleus. Our findings with WGA-HRP are consistent with the observations by Schwab et al. who reported (-125I) WGA is a highly sensitive retrograde tracer (Brain Research 152:145, 1978 (22)).

Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport

MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by γ-interferon

FOR SEVERAL WEEKS prior to the formation of mature muscle cells, the process of which is virtually completed by the fifth fetal month in humans,1the cell exists as a myotube. Similar muscle cells were seen in the biopsy of an adolescent boy with a muscle-wasting disorder. Since this unusual pathological occurrence appears to be unique, it is the purpose of this report to present the clinical, pathological, cytochemical, and electron microscopic studies of this disease. An attempt will also be made to correlate these findings with previously reported studies in myogenesis. Methods Biopsy specimens of gastrocnemius muscle were removed on two separate occasions (September 1962 and January 1965) after infiltration of the overlying skin with a local anesthetic. The initial specimen was removed with sutures and fixed in Zenker's solution; the second specimen was removed with a C-shaped clamp designed for that purpose, and fixed in Bouin's solution.

Nicholas K. Gonatas

Papers

Ultrastructural studies in alzheimer's presenile dementia.

The ultrastructure of a mammalian cell during the mitotic cycle

Superior sensitivity of conjugates of horseradish peroxidase with wheat germ agglutinin for studies of retrograde axonal transport

MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by γ-interferon

Myotubular myopathy. Persistence of fetal muscle in an adolescent boy.