The Schizosaccharomyces pombe rad3 checkpoint gene.

The rad3 gene of Schizosaccharomyces pombe is required for checkpoint pathways that respond to DNA damage and replication blocks. We report the complete rad3 gene sequence and show that rad3 is the homologue of Saccharomyces cerevisiae ESR1 (MEC1/SAD3) and Drosophila melanogaster mei-41 checkpoint genes. This establishes Rad3/Mec1 as the only conserved protein which is required for all the DNA structure checkpoints in both yeast model systems.

Cerebral oxygenation measured by near infrared spectroscopy during cardiopulmonary bypass and deep hypothermic circulatory arrest in piglets.

Near infrared spectroscopy (NIRS) shows large changes in cerebral oxyhemoglobin (Hbo2), deoxyhemoglobin (Hb), and oxidation state of cytochrome aa3 (Cyto2) in infants undergoing cardiopulmonary bypass and deep hypothermic circulatory arrest (CPB-DHCA). To evaluate the physiologic significance of these clinical NIRS measurements, we applied the technique in a piglet model of CPB-DHCA. After an initial stabilization period on CPB, animals (n = 8) were cooled to 15 degrees C, subjected to DHCA for 1 h, then reperfused with rewarming and monitored for 180 min.

Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein.

Presence of the epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD), although the mechanism(s) by which it confers this risk is unknown. ApoE may play a direct role in AD neuropathology by modulating neuronal structure. We previously showed that apoE3-containing beta-very low density lipoprotein (beta-VLDL) can stimulate neurite outgrowth to a significantly greater extent than apoE4-enriched beta-VLDL in a central nervous system-derived neuronal cell line and that this effect is mediated by interaction with the low density lipoprotein receptor-related protein (LRP).

Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome.

To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation.

The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.

A number of cell-cycle checkpoint genes have been shown to play important roles in meiosis. We have characterized the human and mouse counterpart of the Schizosaccharomyces pombe Rad3 protein, named Atr (for ataxia-telangiectasia- and rad3-related), and the protein that is mutated in ataxia-telangiectasia, Atm. We demonstrate that ATR mRNA and protein are expressed in human and mouse testis.

Nerve growth factor and the neurotrophic factor hypothesis.

The discovery of nerve growth factor (NGF) over 40 years ago led to the formulation of the "Neurotrophic Factor Hypothesis". This hypothesis states that developing neurons compete with each other for a limited supply of a neurotrophic factor (NTF) provided by the target tissue. Successful competitors survive; unsuccessful ones die.

Cerebral metabolic recovery from deep hypothermic circulatory arrest after treatment with arginine and nitro-arginine methyl ester.

Background: Recent studies suggest that nitric oxide is important in the pathogenesis of ischemic brain injury and also has a role in controlling cerebrovascular tone. This study examines the net effects of nitric oxide on cerebral metabolic recovery after deep hypothermic circulatory arrest.

Methods: Two-week-old piglets were supported by cardiopulmonary bypass and cooled to 15 degrees C followed by 1 hour of deep hypothermic circulatory arrest, 45 minutes of reperfusion and rewarming, and then 3 hours of normothermic perfusion.

Expression of neuronal-NOS in developing basal forebrain cholinergic neurons: regulation by NGF.

Nerve growth factor (NGF) acts through the receptor tyrosine kinase trkA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band. We have previously shown that the neuronal isoform of nitric oxide synthase (NOS) is selectively expressed in a large fraction of trkA-expressing cholinergic neurons in these brain regions in the adult rat, and that NGF induces the expression of neuronal-NOS in these cells. Herein, we show that: 1) neuronal-NOS is also localized to these neurons in the developing septum; 2) the expression of neuronal-NOS is regulated in the developing medial septal nucleus and vertical limb of the diagonal band; 3) neuronal-NOS regulation parallels that for other markers of basal forebrain cholinergic neuron differentiation, such as cholineacetyltransferase; and 4) NGF infusion in the postnatal period induces robust increases in neuronal-NOS mRNA and in NOS activity in the basal forebrain.

A comprehensive study of the spatiotemporal pattern of beta-amyloid precursor protein mRNA and protein in the rat brain: lack of modulation by exogenously applied nerve growth factor.

Nerve growth factor (NGF) is a neurotrophic factor for basal forebrain cholinergic neurons, a population that degenerates and dies in Alzheimer's disease (AD). It has been suggested that NGF be used to treat AD patients. However, in vivo administration of NGF to the developing hamster brain was shown to induce the expression of the beta-amyloid precursor protein (beta APP) gene.

Influence of age on cerebral recovery after deep hypothermic circulatory arrest in piglets.

Background: In the first weeks of life there are important maturational changes in the central nervous system in many species in energy metabolism, synapse number, and concentration of neuronal excitatory receptors.

Methods: Four groups of 10 piglets (aged 1, 2, 4, and 10 weeks) underwent 1 hour of deep hypothermic circulatory arrest at 15 degrees C, with cooling and rewarming on cardiopulmonary bypass. Cerebral blood flow and metabolic rate measurements and electroencephalographic recordings were obtained from 5 animals per group.

Population estimates of household firearm storage practices and firearm carrying in Oregon.

Objectives: To examine statewide data on exposure of adults and children to loaded and unlocked household firearms, and to estimate the prevalence of firearm carrying among adults in Oregon.

Design: Analyses of 1992 and 1993 telephone survey data from 6202 adults aged 18 years and older using the Oregon Behavioral Risk Factor Surveillance System.

Main Outcome Measures: Number of adults and children exposed to household firearms always or sometimes stored loaded and unlocked.

Neonatal mice lacking neuronal nitric oxide synthase are less vulnerable to hypoxic-ischemic injury.

We hypothesized that elimination of neuronal nitric oxide synthase (nNOS) by targeted disruption of the nNOS gene would result in amelioration of damage seen after hypoxia-ischemia in the developing brain since nitric oxide (NO) has been implicated in glutamate-mediated neurotoxicity after ischemia. Both wildtype and nNOS-deficient pups were subjected to focal ischemia followed by 1.5 h of hypoxia at Postnatal Day 7.

Relative phosphocreatine and nucleoside triphosphate concentrations in cerebral gray and white matter measured in vivo by 31P nuclear magnetic resonance.

Rates of ATP metabolism generally are higher in cerebral gray matter compared to white matter. In order to study the physiology of this regional difference in vivo, the 1-dimensional chemical shift imaging technique (1D-CSI) was used to acquire 31P nuclear magnetic resonance spectra from 2.5 mm slices of 4-week old piglet brains.

Nevermore: the hymen and the loss of virginity.

A major milestone in a woman's life is the loss of virginity, "defloration," with the breaking of the hymen. Psychoanalysis has paid little attention to the meaning of defloration to either women or men, and virtually none to the hymen as a part of the female genitalia. The reasons for this disregard or avoidance are explored.

'Hot spots' of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus.

Creatine kinase (CK) isoenzymes, with emphasis on the mitochondrial CK isoenzymes, were characterized and localized in chicken cerebellum. Chicken cerebellum extracts analyzed by two-dimensional gels, using antipeptide antibodies specific for sarcomeric muscle-type mitochondrial CK (Mib-CK) and revealed the presence of a Mib-CK variant in avian cerebellum. This CK isoform was localized by immunofluorescence staining exclusively in the Purkinje neurons.

Phosphocreatine and creatine kinase in piglet cerebral gray and white matter in situ.

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter.

Nerve growth factor protects the neonatal brain against hypoxic-ischemic injury.

Nerve growth factor (NGF) has been shown to protect specific neurons that express its signaling receptor, trkA, from a variety of insults. There are some data, in particular in the developing brain, indicating that NGF has neuroprotective actions that extend beyond cells expressing trkA. In this study, we asked whether NGF would protect against brain injury in a neonatal model of hypoxia-ischemia.

Creatine and nucleoside triphosphates in rat cerebral gray and white matter.

In vivo localized nuclear magnetic resonance spectroscopy has shown three-fold higher phosphocreatine/nucleoside triphosphate (PCr/NTP) ratios in cerebral white compared to gray matter. To interpret these results, total creatine (Cr) and ATP concentrations were measured enzymatically in samples taken from rapidly frozen rat cerebral cortex and corpus callosum. Total Cr (PCr plus Cr) and ATP concentrations were the same in the two regions.

Parent and peer communication effects on AIDS-related behavior among U.S. high school students.

Data from a 1989 national probability sample of 8,098 high school students in the United States indicate that young people's discussions about the human immunodeficiency virus (HIV) with parents and with peers are highly correlated and have opposite effects on behavior. Students who discussed HIV with their parents were less likely than those who did not to have had multiple sex partners, to have had unprotected sexual intercourse and to have ever injected drugs; on the other hand, students who discussed HIV with their peers were more likely than those who did not to have had multiple partners and to have had unprotected sexual intercourse. Subgroup analyses show that young women were influenced more by HIV discussions with parents, while young men were influenced more by discussions with peers; some communication effects differed by race and ethnicity.

Selective inhibition of axon outgrowth by antibodies to NGF in a model of temporal lobe epilepsy.

The molecular basis of the axonal reorganization that follows seizure-induced brain injury is unknown. Elevations in neurotrophins following seizures suggest that growth factors may play a role in this process. After pilocarpine-induced seizures, robust axonal sprouting from dentate granule cells and cholinergic forebrain neurons was evident in the inner molecular layer of the dentate gyrus.

Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.

The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified.

Enamel hypoplasia, bilateral cataracts, and aqueductal stenosis: a new syndrome?

We report on a 12-year-old girl who presented with generalized enamel hypoplasia, cataracts, and enlargement of the cerebral ventricles secondary to aqueductal stenosis. Previously described syndromes of enamel defects with or without cataracts were excluded on the basis of clinical criteria and appearance of the dentition. Metabolic conditions which could have caused cataracts were excluded clinically and by biochemical tests.

Trends in risk behaviors for HIV infection among U.S. high school students, 1989-1991.

The objective of this study was to examine trends in rates of self-reported HIV-related instruction and behaviors among high school students in the United States. Self-administered questionnaires were completed by three independent, multistage national probability samples of public and private school students in grades 9 through 12 who were surveyed in the spring of 1989, 1990, and 1991, respectively. Controlling for demographic characteristics, we used logistic regression to test for trends from 1989 to 1991.

Elements in the 5' flanking sequences of the mouse low-affinity NGF receptor gene direct appropriate CNS, but not PNS, expression in transgenic mice.

We have initiated a characterization of the cis-acting regulatory elements of the murine low-affinity NGF receptor (p75NGFR) gene. Despite studies in cultured cells that suggest the p75NGFR promoter is constitutive, a detailed analysis of this promoter in five lines of transgenic mice demonstrated a high degree of cell-type specificity: 8.4 kb of 5' flanking sequence directs expression of a lacZ reporter to retinal and CNS neurons normally expressing p75NGFR.