Human endopeptidase (THOP1) is localized on chromosome 19 within the linkage region for the late-onset alzheimer disease AD2 locus.

A cDNA encoding the rat endopeptidase 24.15 was used to determine the chromosomal localization of the respective human gene. Hybridization to DNA from human-rodent somatic cell hybrids assigned the human gene to chromosome 19.

Plasma and cerebrospinal fluid hyperinsulinism in asphyxiated piglets.

Insulin (I) plays a crucial role in the maturation of the perinatal brain, and it may also be involved in the pathogenesis of neonatal brain injuries. The aim of the present study was to reveal the effect of neonatal asphyxia on the regulation of I and glucose (G) metabolism in plasma and cerebrospinal fluid (CSF) in newborn piglets. The I concentrations were measured by radioimmunoassay, while the G levels were analyzed by the G oxidase method during three phases (basal, critical, recovery) of bilateral pneumothorax in newborn piglets.

Allele epsilon 4 of apolipoprotein E shows a dose effect on age at onset of Pick disease.

Pick disease is a rare progressive dementing illness characterized by severe atrophy of the frontal and temporal lobes. Clinically, Pick disease may be difficult to distinguish from Alzheimer disease (AD). The fact that Pick disease is often familial, and the evidence suggesting that the epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for AD and possibly other dementias, prompted us to study ApoE isoforms in Pick disease.

Purification of the adenomatous polyposis coli (APC) gene product.

Mutation of the adenomatous polyposis coli (APC) gene is responsible for familial adenomatous polyposis and is an etiologic factor for digestive tract malignancies. Although the APC gene product (APC) is believed to play a role in growth suppression of colonocytes, the underlying mechanism is not clear. However, recent evidence does suggest that APC is a microtubule-associated protein (MAP), and like other MAPs, it can be phosphorylated, as we have shown.

Exposure of tumor necrosis factor-alpha to luminal membrane of bovine brain capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cytoplasmic stress fiber formation of actin.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has long been known to be involved in the pathogenesis of central nervous system infections and of certain neurodegenerative diseases. However, the possible role of the blood-brain barrier (BBB), the active interface between the blood circulation and brain tissue, remained unknown during these pathological conditions. In our in vitro reconstructed BBB model, 1-hr exposure of recombinant human TNF-alpha (in concentrations of 50, 250, and 500 U/ml, respectively) to the luminal membrane of bovine brain capillary endothelial cells (BBCEC) did not change significantly the transendothelial flux of either sucrose (m.

The role of cerebral microvessels in the elimination of histamine released during postasphyxial reperfusion in newborn piglets.

Histamine, released from intracerebral sources during hypoxic-ischemic conditions, may take part in the pathogenesis of neonatal brain injuries. In order to elucidate the possible role of cerebral microvessels in the elimination of histamine from the extracellular space, we determined the concentration of histamine using a modified radioenzymatic method in plasma taken from the internal jugular vein, in cerebrospinal fluid, and in capillary-rich fraction of cerebral microvessels prepared from cortex in 12 sham-operated piglets. Then, bilateral pneumothorax was induced in 20 piglets, samples were taken from the same compartments as from the controls before and during asphyxia, as well as 15 and 180 min thereafter, respectively.

Penetration of small molecular weight substances through cultured bovine brain capillary endothelial cell monolayers: the early effects of cyclic adenosine 3',5'-monophosphate.

Second messengers, such as cyclic adenosine 3',5'-monophosphate (cAMP), have been shown to take part in the regulation of blood-brain barrier permeability. In the present study, elevation of cAMP levels decreased sucrose (mol. wt, 342) and inulin (mol.

Immunodetection of the presence or absence of full-length APC gene product in human colonic tissues.

In order to detect the presence or absence of wild-type adenomatous polyposis coli (APC) gene protein (APC) in human colonic tissues, we immunoaffinity purified two polyclonal rabbit antibodies (APC-1 and APC-2) directed against defined epitopes in the middle and carboxyl regions of APC. Such antibodies proved useful in western blot analysis of matched colonic mucosa and tumor sample pairs. A 300 kDa band corresponding to APC was detected in samples from normal colonic mucosa using both antibodies.

Protection against HIV-1 gp120-induced brain damage by neuronal expression of human amyloid precursor protein.

Expression of the HIV-1 envelope protein gp120 in brains of transgenic (tg) mice induces extensive neurodegeneration (Toggas, S. M., E.

The WHO objectives for palliative care: to what extent are we achieving them?

This paper examines recent research in palliative care in the light of the guiding principles set out by the World Health Organization. It outlines the gaps in the literature and suggests priorities for future research. Areas of unmet need are documented and it is argued that research comparing outcomes across care settings and relating particular care practices to outcome measures would help to set care targets.

Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.

A radioimmunoassay (RIA) has been developed for the adenomatous polyposis coli protein (APC). High-avidity rabbit polyclonal antibodies were produced against synthetic peptides corresponding to amino acids 1865-1881 (APC-1) and to amino acids 1336-1350 (APC-2) in APC's 2844 amino acid sequence. Both antibodies were utilized in RIA to evaluate full-length APC that is present in the insoluble particulate fraction of cell lysates.

Elastase given intracisternally opens blood-brain barrier in newborn piglets.

The effect of elastase on the blood-brain barrier (BBB) permeability was intravitally studied by fluorescence photomacroscope using the open cranial window technique in newborn piglets. Eleven animals (group 1) were given intracisternal injection of porcine elastase (1.0 micrograms), while 7 piglets served as controls (group 2).

Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice.

The amyloid precursor protein (APP) is involved in Alzheimer's disease (AD) because its degradation products accumulate abnormally in AD brains and APP mutations are associated with early onset AD. However, its role in health and disease appears to be complex, with different APP derivatives showing either neurotoxic or neurotrophic effects in vitro. To elucidate the effects APP has on the brain in vivo, cDNAs encoding different forms of human APP (hAPP) were placed downstream of the neuron-specific enolase (NSE) promoter.

Measurement of condom use in 72 studies of HIV-preventive behaviour: a critical review.

Ninety-four distinct measures of condom use were identified in a review of 72 psychosocial studies of HIV-prevention. A coding scheme was developed which characterised each measure in terms of: (1) type of measure (e.g.

Biguanide derivatives: agonist pharmacology at 5-hydroxytryptamine type 3 receptors in vitro.

The effects of 24 biguanide and four guanidine derivatives on 5-hydroxytryptamine (5-HT)3 receptors in N1E-115 neuroblastoma cells were examined using radioligand binding and whole-cell voltage-clamp techniques. Displacement of the selective 5-HT3 receptor antagonist [3H]BRL 43694 by phenylbiguanide (PBG) derivatives revealed Ki values ranging from 3.4 x 10(-4) to 4.

Modelling and modifying young heterosexuals' HIV-preventive behaviour; a review of theories, findings and educational implications.

Studies applying social cognitive frameworks such as the health belief model and the theory of reasoned action to HIV-prevention are reviewed. These models suggest that appropriate beliefs, attitudes, social norms, intentions and perceived self-efficacy are sufficient psychological conditions for safer sexual behaviour. Limitations inherent in these accounts are identified and additional factors which need to be incorporated in psychological models and health education programmes are highlighted.

Exploring teenagers' adaptive and maladaptive thinking in relation to the threat of hiv infection.

Teenagers' HIV-preventive cognitions were explored within a protection motivation theory framework. Five hundred and seven adolescent men and women from two cohorts (sixteen and eighteen) completed a confidential postal questionnaire. The effect of demographic variables, previous sexual experience and appraisal of threat and coping resources upon HIV-relevant cognitions was investigated using path analysis.

Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice.

Many people infected with human immunodeficiency virus type 1 (HIV-1) develop neurological complications that can culminate in dementia and paralysis. The discrepancy between the severity of impairment and the paucity of detectable HIV-1 within neurons has led to an intense search for diffusible virus- and host-derived factors that might be neurotoxic (see ref. 2 for review).