Here are some of the juciest of the results of the simple MEDLINE search:
RECORD NO.: 96358483
AUTHOR: Laurent M
ADDRESS: Service d'Imagerie Cellulaire, URA 1116, Universite Paris-
Sud, Centre d'Orsay, France.
TITLE: Prion diseases and the 'protein only' hypothesis: a
theoretical dynamic study.
SOURCE: Biochem J (9YO), 1996 Aug 15; 318 ( Pt 1) 35-9
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ANNOUNCEMENT: 9611
PUB. TYPE: JOURNAL ARTICLE
ABSTRACT: In the 'protein only' hypothesis, prion diseases are thought
to result from the conformational change of a normal isoform
of a prion protein (PrPC) to a protease-resistant,
pathogenic form called PrPSc. This conversion rests on an
autocatalytic process requiring the presence of pre-existing
PrPSc. Theoretical kinetic analysis of the dynamic process,
including the turnover of the normal prion protein, shows
that the system exhibits bistability properties, indicating
that the very slow accumulation of the abnormal form of the
protein in the brain could in fact be the consequence and
not the cause of the disorders. The cause would be a
transition between two alternative steady states of the
system. The presence of a small amount of the PrPSc protein
in lymphocytes does not necessarily constitute any
indication of a non-symptomatic but infectious pathogenic
state. Moreover, infectious prion particles should not be
seen as necessarily composed of the abnormal isoform of the
protein, as usually stated. Particles containing only an
excess of the normal form of the protein might also be
pathogenic. Compounds that can act on the turnover rate of
the normal PrPC protein could be a therapeutic strategy
against prion diseases.
MESH HEADINGS: Prion Diseases--metabolism (*ME); PrPC Proteins--chemistry
(CH)/metabolism (*ME); PrPSc Proteins--chemistry
(CH)/metabolism (*ME); Cattle; Kinetics; Protein
Conformation; Animal; Human; Support, Non-U.S. Gov't
CHEMICAL SUBS: 0 (PrPC Proteins); 0 (PrPSc Proteins)
STANDARD NO.: 0264-6021
DATES: Entered 960926
RECORD NO.: 96365284
AUTHOR: Collinge J
TITLE: New diagnostic tests for prion diseases [editorial; comment]
SOURCE: N Engl J Med (NOW), 1996 Sep 26; 335 (13): 963-5
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ANNOUNCEMENT: 9611
PUB. TYPE: COMMENT; EDITORIAL
NOTES: Comment on: N Engl J Med, 1996 Sep 26;335(13):924-30
MESH HEADINGS: Cerebrospinal Fluid Proteins--analysis (*AN); Creutzfeldt-
Jakob Syndrome--cerebrospinal fluid (CF)/diagnosis (*DI);
Prion Diseases--cerebrospinal fluid (CF)/transmission
(TM)/diagnosis (*DI); Proteins--analysis (*AN); Biological
Markers--cerebrospinal fluid (CF); Human
CHEMICAL SUBS: 0 (brain 14-3-3 protein); 0 (Biological Markers); 0
(Cerebrospinal Fluid Proteins); 0 (Proteins)
STANDARD NO.: 0028-4793
DATES: Entered 960926
RECORD NO.: 96195875
AUTHOR: Prusiner SB
ADDRESS: Department of Neurology, University of California, San
Francisco 94143-0518, USA.
TITLE: Transgenetics of prion diseases.
SOURCE: Curr Top Microbiol Immunol (DWQ), 1996; 206 275-304
LANGUAGE: English
COUNTRY PUB.: GERMANY
ANNOUNCEMENT: 9608
PUB. TYPE: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
NUMBER REFS.: 134
MESH HEADINGS: Prion Diseases--etiology (ET)/pathology (PA)/genetics (*GE);
Animals, Transgenic; Disease Models, Animal; Gene Targeting;
Mice; Prions--genetics (GE)/pathogenicity (PY); Scrapie--
etiology (ET)/genetics (GE); Animal; Human; Support, Non-
U.S. Gov't; Support, U.S. Gov't, P.H.S.
CHEMICAL SUBS: 0 (Prions)
GRANT NO.: NS14069; NS; NINDS; AG08967; AG; NIA; AG02132; AG; NIA; +
STANDARD NO.: 0070-217X
DATES: Entered 960530
RECORD NO.: 96071228
AUTHOR: Blakemore WF
TITLE: Observations on oligodendrocyte degeneration, the resolution
of status spongiosus and remyelination in cuprizone
intoxication in mice.
SOURCE: J Neurocytol (JB3), 1972 Dec; 1 (4): 413-26
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ANNOUNCEMENT: 9604
PUB. TYPE: JOURNAL ARTICLE
MESH HEADINGS: Cuprizone--poisoning (*PO); Myelin Sheath--drug effects
(*DE); Nerve Degeneration--physiology (*PH);
Oligodendroglia--physiology (*PH); Prion Diseases--
chemically induced (*CI); Mice; Mice, Inbred Strains;
Animal; Male
CHEMICAL SUBS: 370-81-0 (Cuprizone)
STANDARD NO.: 0300-4864
DATES: Entered 960129
RECORD NO.: 96020175
AUTHOR: Parchi P; Gambetti P
ADDRESS: Division of Neuropathology, Case Western Reserve University,
Cleveland, Ohio, USA.
TITLE: Human prion diseases.
SOURCE: Curr Opin Neurol (BX4), 1995 Aug; 8 (4): 286-93
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ANNOUNCEMENT: 9602
PUB. TYPE: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
NUMBER REFS.: 55
ABSTRACT: Major advances have been made in prion diseases. Recent data
indicate that the prion protein is likely to be a synaptic
protein with a functional role in synaptic transmission. An
impressive body of evidence suggests that (1) the normal
prion protein plays a central role in prion replication; (2)
the replication process implies an interaction between the
normal prion protein and the pathogenic prion protein; and
(3) the pathogenic prion protein is the infectious agent,
the infectivity of which is dependent on its abnormal
conformation. Genetic and protein analyses have expanded the
spectrum of prion diseases and have underlined the
complexity of genotype-phenotype interactions.
MESH HEADINGS: Dementia, Senile--genetics (GE)/pathology (PA)/diagnosis
(*DI); Prion Diseases--genetics (GE)/pathology
(PA)/diagnosis (*DI); Adult; Aged; Genotype; Mice; Mice,
Transgenic; Middle Age; Phenotype; Prions--genetics (GE);
Synaptic Transmission--genetics (GE); Animal; Female; Human;
Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
CHEMICAL SUBS: 0 (Prions)
GRANT NO.: AG08012; AG; NIA; AGNS08155; AG08992; AG; NIA
STANDARD NO.: 1350-7540
DATES: Entered 951212
RECORD NO.: 96030866
AUTHOR: Beekes M; Baldauf E; Cassens S; Diringer H; Keyes P; Scott
AC; Wells GA; Brown P; Gibbs CJ Jr; Gajdusek DC
ADDRESS: Robert Koch-Institut, Bundesinstitut fur
Infektionskrankheiten und nicht ubertragbare Krankheiten,
Berlin, Germany.
TITLE: Western blot mapping of disease-specific amyloid in various
animal species and humans with transmissible spongiform
encephalopathies using a high-yield purification method.
SOURCE: J Gen Virol (I9B), 1995 Oct; 76 ( Pt 10) 2567-76
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ANNOUNCEMENT: 9602
PUB. TYPE: JOURNAL ARTICLE
ABSTRACT: SAF-protein, an amyloid, is the main constituent of scrapie-
associated fibrils (SAF) and a specific marker for
transmissible spongiform encephalopathies (TSE). Using an
improved extraction method and Western blot detection, the
disease-specific amyloid was found in various parts of the
central nervous system of hamsters orally infected with
scrapie, of squirrel monkeys orally infected with kuru,
sporadic Creutzfeldt-Jakob disease (CJD) and scrapie, of
human patients with sporadic CJD, of a sheep with natural
scrapie and of a cow with bovine spongiform encephalopathy
(BSE). In human CJD samples, the concentration of TSE-
specific amyloid was estimated to be 1000- to 10 000-fold
lower than in the central nervous system of hamsters with
scrapie. The extraction method has a yield of 70% and allows
Western blot detection of the TSE-specific amyloid in
samples representing 1-10 micrograms of brain tissue from
intracerebrally infected hamsters, as well as in individual
spleens from hamsters with terminal scrapie infected by the
intracerebral, oral or intraperitoneal route. A 20-100 mg
sample of material is sufficient for the extraction of the
pathological protein from different rodent, monkey, ovine,
bovine and human tissues. The results reported here
demonstrate the potential suitability of the method for the
routine diagnosis of TSE as well as for the detailed
analysis of distribution patterns of the TSE-specific
amyloid in experimental approaches to the investigation of
these diseases.
MESH HEADINGS: Amyloid--isolation & purification (*IP); Blotting, Western--
methods (*MT); Central Nervous System--chemistry (*CH);
Prion Diseases--diagnosis (DI)/veterinary (VE)/metabolism
(*ME); Cattle; Hamsters; Mesocricetus; Protein Precursors--
analysis (AN); Proteins--analysis (AN); Saimiri; Sheep;
Spleen--chemistry (CH); Animal; Female; Human; Support, Non-
U.S. Gov't
CHEMICAL SUBS: 0 (amyloid fibril protein SAF); 0 (Amyloid); 0 (Protein
Precursors); 0 (Proteins)
STANDARD NO.: 0022-1317
DATES: Entered 951128
RECORD NO.: 96341236
AUTHOR: Tranchant C; Rodier G; Schmitthaeusler R; Warter JM
ADDRESS: Service des Maladies du Systeme Nerveux et du Muscle,
Hopitaux Universitaires de Strasbourg.
TITLE: [Amyloidosis, protein conformation dynamics and neurologic
diseases]. Amylose, dynamique conformationnelle des
proteines et maladies neurologiques.
SOURCE: Rev Neurol (Paris) (SU9), 1996 Mar; 152 (3): 153-7
LANGUAGE: French
COUNTRY PUB.: FRANCE
ANNOUNCEMENT: 9612
PUB. TYPE: English Abstract; JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
NUMBER REFS.: 26
ABSTRACT: The abnormal protein which accumulates in the extracellular
space in the central nervous system in Alzheimer's disease
and prion diseases could result from similar mechanisms.
Many studies have demonstrated that the abnormal protein is
resistant to proteolytic agents. This resistance is
correlated with a modification in the conformation of the
protein, inverting the ratio of alpha and beta helix
structures. This change in conformation could be the cause
of the central nervous system lesions. The mechanism of the
modification in conformation could be related to a process
of hydrophobisation of the protein resulting from mutation.
A hydrophilic amino acid would be replaced by a hydrophobic
amino acid or in sporadic forms, modifications in the
environment of the peptide may lead to physical and chemical
aggressions. Hydrophobisation of the two proteins could
later lead to formation of polymers and then insoluble
aggregates with the physical and chemical characteristics of
the amyloid substance. Polymerisation could be triggered by
the formation of protein dimers which would be, in one case,
an endogenous protein, PrP, and in the other exogenous
proteins coming from the environment.
MESH HEADINGS: Amyloidosis--genetics (GE)/physiopathology (*PP); Nervous
System Diseases--genetics (GE)/physiopathology (*PP);
*Protein Conformation; Alzheimer's Disease--genetics
(GE)/physiopathology (PP); Amyloid beta-Protein--chemistry
(CH)/genetics (GE); Prion Diseases--genetics
(GE)/physiopathology (PP); Prions--chemistry (CH)/genetics
(GE); Human
CHEMICAL SUBS: 0 (Amyloid beta-Protein); 0 (Prions)
STANDARD NO.: 0035-3787
DATES: Entered 961010
RECORD NO.: 96401547
AUTHOR: Barron KD
ADDRESS: Department of Neurology, Albany Medical College, NY 12208,
USA.
TITLE: The microglial cell. A historical review.
SOURCE: J Neurol Sci (JBJ), 1995 Dec; 134 Suppl 57-68
LANGUAGE: English
COUNTRY PUB.: NETHERLANDS
ANNOUNCEMENT: 9612
PUB. TYPE: HISTORICAL ARTICLE; JOURNAL ARTICLE; REVIEW; REVIEW,
TUTORIAL
NUMBER REFS.: 88
ABSTRACT: Effectively, modern research has confirmed Hortega's view of
the origin of the microgliacyte from circulating monocytes
of the monocyte-macrophage series that invade the brain
during embryonic and early postnatal life. Their phagocytic
capacity is exercised during the brain remodelling that
marks brain maturation. They then convert to the ramified
resting microglial cell visualized in the silver carbonate
staining technique of Hortega and by modern lectin-binding
methods. In response to injury, reactive microglia exhibit
hypertrophy and hyperplasia, and may or may not go on to
form typical lipid-laden phagocytes. Activated microglia
show upregulation of the many marker antigens they share
with circulating monocytes, including the major
histocompatibility class (MHC) class II antigens that
bespeak their immunocompetent nature. However, MHC class I
and II expression and development of immunohistochemical
positivity for cytoplasmic and plasma membrane antigens that
characterize the monocyte-macrophage do not necessarily
indicate an immunological response though there is ample
evidence that microglia can serve as antigen-presenting
cells. Rather, microglia are extraordinarily sensitive to
changes in the brain microenvironment, whatever the nature
of the exciting mechanism or substance. They may be
considered to serve an ever alert, protective and supportive
function that can be assembled rapidly to deal with
infections, physical injuries, physiologic changes and
systemic influences. In addition to elaboration and
secretion of cytokines with varied actions, e.g.,
suppression of astrogliosis, they secrete factors, including
nerve growth factor, which are supportive of neurons. They
have an important role in iron metabolism and the storage of
iron and ferritin. They may promote central nervous system
regeneration. They are prominently involved in such
pathologic processes as the acquired immunodeficiency
syndrome, multiple sclerosis, prion diseases and the
degenerative disorders, e.g., Alzheimer's disease and
Parkinson's disease. With aging, they grow more numerous,
become richer in iron and ferritin and exhibit phenotypic
alteration, e.g., the expression of MHC class II antigens
that are not ordinarily demonstrable immunohistochemically
in the resting state. The rate of growth of our knowledge of
microglia during the last decade has been exponential and
continues.
MESH HEADINGS: Microglia--metabolism (ME)/physiology (*PH); Axons--
physiology (PH); History of Medicine, 20th Cent.; Iron--
metabolism (ME); Neurology--history (HI); Animal; Human;
Support, U.S. Gov't, Non-P.H.S.
CHEMICAL SUBS: 7439-89-6 (Iron)
STANDARD NO.: 0022-510X
DATES: Entered 961024
RECORD NO.: 96298695
AUTHOR: Hope J; Shearman MS; Baxter HC; Chong A; Kelly SM; Price NC
ADDRESS: BBSRC & MRC Neuropathogenesis Unit, BBSRC Institute for
Animal Health, Edinburgh.
TITLE: Cytotoxicity of prion protein peptide (PrP106-126) differs
in mechanism from the cytotoxic activity of the Alzheimer's
disease amyloid peptide, A beta 25-35.
SOURCE: Neurodegeneration (B99), 1996 Mar; 5 (1): 1-11
LANGUAGE: English
COUNTRY PUB.: ENGLAND
ANNOUNCEMENT: 9611
PUB. TYPE: JOURNAL ARTICLE
ABSTRACT: The abnormal form of the prion protein (PrPSc), a synthetic
prion protein peptide fragment (PrP106-126) and fragments of
the Alzheimer's protein precursor, APP, have been shown to
be cytotoxic in vitro. We have used synchronous, clonal cell
models originally developed to study the toxicity of the
Alzheimer's disease amyloid peptide, A beta 25-35, to
investigate the actions of PrP peptides. We found that the
cytotoxicity of the PrP106-126 depends on its state of
aggregation and the cellular expression of PrPc, and is
independent of a loss of MTT reduction activity in the
absence of cell death associated with the cellular effects
of A beta 25-35. These factors may play a role in the lesion
specificity of different pathological phenotypes of prion-
protein related diseases.
MESH HEADINGS: Amyloid beta-Protein--chemistry (CH)/toxicity (*TO); Cell
Survival--drug effects (*DE); Neurotoxins--toxicity (*TO);
Peptide Fragments--chemistry (CH)/chemical synthesis
(CS)/toxicity (*TO); Prions--chemistry (CH)/chemical
synthesis (CS)/toxicity (*TO); PrPC Proteins--chemistry
(CH)/biosynthesis (*BI); Amino Acid Sequence; Circular
Dichroism; Dose-Response Relationship, Drug; Gene
Expression; Hela Cells; Kinetics; Lactate Dehydrogenase;
Mice; Molecular Sequence Data; Neuroblastoma; Neurons--
cytology (CY)/drug effects (DE); PC12 Cells; Rats; Tumor
Cells, Cultured; Animal; Comparative Study; Human
CHEMICAL SUBS: EC 1.1.1.27 (Lactate Dehydrogenase); 0 (amyloid beta-protein
(25-35)); 0 (prion protein (106-126)); 0 (Amyloid beta-
Protein); 0 (Neurotoxins); 0 (Peptide Fragments); 0
(Prions); 0 (PrPC Proteins)
STANDARD NO.: 1055-8330
DATES: Entered 960924
RECORD NO.: 96155568
AUTHOR: Hogan RN; Cavanagh HD
ADDRESS: Department of Ophthalmology, University of Texas
Southwestern Medical Center at Dallas 75235-9057, USA.
TITLE: Transplantation of corneal tissue from donors with diseases
of the central nervous system [see comments]
SOURCE: Cornea (DSN), 1995 Nov; 14 (6): 547-53
LANGUAGE: English
COUNTRY PUB.: UNITED STATES
ANNOUNCEMENT: 9605
PUB. TYPE: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
NUMBER REFS.: 67
ABSTRACT: A great deal of controversy and concern exists over
potential transmission of central nervous system diseases by
corneal transplant. The purpose of this study was to
evaluate the available data relative to this question,
pertaining especially to transmission of infectious
dementia. From these data, determination of conveyance risks
are possible, and rational policies for donor inclusion
criteria can be constructed. Retrospective analysis of
available published data regarding transmission of
infectious dementias was performed. Risk of disease
transmission was calculated from population data. Of the
various forms of dementia, only rabies, hepatitis B, and
Creutzfeldt-Jakob disease (CJD) have been transmitted by
corneal transplantation. Transmission of the first two
viruses is preventable by serologic testing. Prevention of
CJD transmission relies on clinical history. Despite the
possibility of transmission and the lack of available
testing, slow virus disease (CJD) has been transmitted only
once. That this case represents an extremely rare event is
supported by a lack of successful transmission via corneal
transplant in monkeys; lower levels of infectious agent in
cornea than in brain; lack of successful transmission of
similar human dementias, including Alzheimer's disease to
primates; the apparent requirement for homozygosity at codon
129 of chromosome 20 for transmission; lack of transmission
in 5-10% of CJD cases even after brain inoculation; and low
numerical risk of transmission based on population data.
Only 0.5-4 CJD infected donors per year would be expected.
Current Eye Bank Association of America criteria for donor
exclusion based on suspicious history are adequate to
protect against accidental conveyance of transmissible
dementia.
NOTES: Comment in: Cornea, 1995 Nov;14(6):545-6
MESH HEADINGS: Corneal Diseases--etiology (ET)/prevention & control (*PC);
*Corneal Transplantation; Disease Transmission, Horizontal--
prevention & control (*PC); Prion Diseases--prevention &
control (PC)/transmission (*TM); *Tissue Donors; Callithrix;
Eye Banks--organization & administration (OG)/standards
(ST); Guidelines; Middle Age; Risk Factors; Animal; Human;
Support, Non-U.S. Gov't
STANDARD NO.: 0277-3740
DATES: Entered 960311