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Biomedical subjects

J Summers

Publications and source records attributed to J Summers.

At least 37 records · Page 2Linked to original sources

College women's perceptions regarding resistance to sexual assault.

College women's perceptions about resistance to sexual assault were examined. Twenty-one percent of the 334 women surveyed stated that they had been sexually assaulted. The vast majority of participants had changed their lifestyles to prevent a sexual assault. Less than 1 woman in 5 of those surveyed had taken a self-defense class. Participants believed that resisting sexual assault by a stranger with a weapon was more likely than resisting an unarmed attacker to increase their chances of being physically harmed, raped, or murdered. Twenty-two percent of the participants said they were "very likely" to resist sexual assault by a stranger with a weapon; 52% would resist a stranger without a weapon. The findings indicate the need for an increase in the number of women taking self-defense classes and a revision in women's perceptions about resisting sexual assault.

Adult↗

A novel transcriptional element in circular DNA monomers of the duck hepatitis B virus.

We report the presence of two elements, pet and net, that are required for proper transcription of the duck hepatitis B virus (DHBV). These regions were previously identified by using plasmid clones of the virus in transient expression assays (M. Huang and J. Summers, J. Virol. 68:1564-1572, 1994). In this study, we further analyzed these regions by using in vitro-synthesized circular DHBV DNA monomers to mimic the authentic transcriptional template. We observed that pet was required for pregenome transcription from circular viral monomers, and in the absence of pet-dependent transcription, expression of the viral envelope genes was increased. We found that deletion of net in circularized DNA monomers led to the production of abnormally long transcripts due to a failure to form 3' ends during transcription. In addition, we report the presence of a net-like region in the mammalian hepadnavirus woodchuck hepatitis virus. These results are consistent with a model that net is a region involved in transcription termination and that in DHBV, pet is required for transcription complexes to read through this region during the first pass through net.

Animals↗

Indices of renal tubular function in perinatal asphyxia.

AIMS: To determine and compare two urinary indices of renal tubular function, N-acetyl-glucosaminidase (NAG) and beta 2-microglobulin (beta 2 M), in healthy term neonates and babies with perinatal asphyxia. METHODS: In a prospective case-control study using asphyxiated (n = 35) and normal control (n = 55) infants, urinary NAG and beta 2 M were assayed at 24-48 hours of life, 4-6 days, and 4-6 weeks. RESULTS: NAG and beta 2 M were significantly increased at 24-48 hours and 4-6 days in the asphyxiated infants compared with the controls. Increased NAG values reflect the degree of perinatal asphyxia more than do beta 2 M. Gentamicin also increased NAG excretion, but to a lesser extent than did perinatal asphyxia. CONCLUSIONS: NAG (+/- beta 2 M) may be a useful marker of perinatal asphyxia. Urinary NAG concentrations correlate with the severity of perinatal asphyxia.

Acetylglucosaminidase↗

Increasing return rates to a mail survey among health educators.

This study indicated a combination of methods increased the return rate (80%) in a national survey of health educators (n = 546). Also, use of a $1.00 bill incentive was not significantly more effective than no incentive, and the rate of double responses in this anonymous mail survey was very low (1%).

Adult↗

Covalently closed circular viral DNA formed from two types of linear DNA in woodchuck hepatitis virus-infected liver.

We found that livers from woodchucks chronically infected with woodchuck hepatitis virus (WHV) contained covalently closed circular DNA (cccDNA) molecules with deletions and insertions indicative of their formation from linear viral DNA by nonhomologous recombination, as we previously described for the duck hepatitis B virus (W. Yang and J. Summers, J. Virol. 69:4029-4036, 1995). However, evidence for two different types of linear precursors was obtained by analysis of the recombination joints in WHV cccDNA. Type 1 linear precursors possessed the structural properties that correspond to those of in situ-primed linear DNA molecules, which constitute between 7 and 20% of all viral DNA replicative intermediates synthesized in the liver. Type 2 linear precursors are hypothetical species of linear DNAs with a terminal duplication of the cohesive-end region, between DR1 and DR2. This type of linear DNA has not been previously described and was not detected among the DNA species present in nucleocapsids. A fraction of cccDNAs formed from both type 1 and type 2 linear DNAs are predicted to be functional for further DNA synthesis, and some evidence for the formation of two or more generations of cccDNA from linear DNA was observed.

Animals↗

Pseudomonas aeruginosa wound infection associated with a nursing home's whirlpool bath.

Whirlpool baths are fitted with hydrojet circulation and/or air induction bubble systems. Water in a whirlpool bath, unlike a spa pool, is not filtered or chemically treated but the bath is drained and cleaned between each bather. This is, we believe, the first report of Pseudomonas aeruginosa wound infection associated with the use of a whirlpool bath in a nursing home. Microbiologically confirmed infections with P. aeruginosa of identical antibiotic sensitivity patterns arose in one week in wounds of four of 24 residents who used a whirlpool bath from which P. aeruginosa was also isolated. P. aeruginosa was not isolated from the wounds of a further seven residents who did not use the whirlpool bath. The incident control team advised that use of the whirlpool bath should be restricted to continent residents with intact skin, and that the bath should be cleaned with a degreasing agent and disinfected with hypochlorite between use by individual residents. The hazard of infection posed by whirlpool baths, particularly in nursing homes, needs to be assessed. National guidance for their cleaning, maintenance, and disinfection is required.

Aged↗

Duration illusions in a train of visual stimuli.

The first stimulus in a sequential train of identical flashes of light appears to last longer than those in the middle of the train. Four flashes (each 600 or 667 ms) were presented and the first was shortened until it appeared to have the same duration as that of the next. The duration of the first stimulus was found to be overestimated by about 50%. The illusion was unaffected by stimulus contrast, size, or interflash interval (between 100 and 600 ms). For some subjects, the last stimulus in the train also appeared to be about 50% longer than the penultimate flash. The results are discussed in terms of theories of how attention, arousal, and stimulus processing can affect duration perception. The mechanisms activated are peculiar to the visual system, since no similar illusion of duration was consistently experienced with a train of auditory tones.

Humans↗

Psychiatric morbidity associated with acquired immune deficiency syndrome-related grief resolution.

This study examined acquired immune deficiency syndrome (AIDS)-related grief resolution and psychiatric morbidity in 286 human immunodeficiency virus (HIV)-positive and HIV-negative gay men examined between 1989 and 1993 in San Diego, CA. Psychiatric morbidity, mood ratings, and bereavement assessments were obtained using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scales for Depression and Anxiety, and Texas Revised Inventory of Grief. Sixty percent of the men (N = 171) reported a loss within the previous 12 months. Eighteen percent of the bereaved met criteria for unresolved grief. No differences were evident in lifetime psychiatric disorders, yet men with unresolved grief demonstrated an elevated prevalence of current major depression and panic disorder when compared with resolved grievers. Clinician sensitivity to the grief process and its relationship to psychiatric complications is an important component of comprehensive psychiatric and medical care of men at high risk for HIV during this era of AIDS.

Acquired Immunodeficiency Syndrome↗

High school students' perceptions of nonconsensual sexual activity.

A total of 588 secondary students completed a 25-item survey on perceptions regarding nonconsensual sexual activity. Subjects included an equal percentage of males and females and were predominantely White (61%), freshmen (67%), and of lower academic achievement (< 3.0 GPA = 57%). Females, African Americans, and those with low academic achievement were more likely to perceive that all or most of their same sex peers were having sex. African American students and those with low academic achievement were significantly more likely than White students and students with high academic achievement (> 3.0 GPA) to perceive that all or most of their close friends were having sex. Females were more knowledgeable of nonconsensual sexual activity than were males. Significant differences existed on attitudes and behavioral intentions by gender, race, academic achievement, and perceived sexual activity of close friends.

Adolescent↗

Illegitimate replication of linear hepadnavirus DNA through nonhomologous recombination.

Linear hepadnavirus DNA in primary hepatocyte cultures efficiently participates in intra- and intermolecular nonhomologous recombination at its ends. The products of this recombination are (i) monomeric covalently closed circular DNAs (cccDNAs) with deletions and insertions around the site of joining and (ii) oligomeric forms in which monomers are joined near the ends in random orientation. A fraction of monomeric cccDNAs can serve as intermediates in further DNA replication through at least five generations of nonhomologous recombination in a process we call illegitimate replication. We suggest that the monomeric and oligomeric linear DNAs produced by illegitimate replication may be precursors of the integrated and other high-molecular-weight hepadnaviral DNA forms seen in chronic infection.

Animals↗

Analysis of the binding of a host cell surface glycoprotein to the preS protein of duck hepatitis B virus.

We have previously identified a 180-kDa host cell glycoprotein (gp180) that specifically binds the surface envelope of duck hepatitis B virus (DHBV) and whose binding is inhibited by neutralizing antiviral monoclonal antibodies. Here we map the viral determinants required for gp180 binding to a 66-amino acid region within the preS domain of the envelope coding region. This region includes both major neutralizing preS epitopes previously defined by monoclonal antibodies. Examination of a series of linker-substitution mutations throughout preS indicates that all mutations that block gp180 binding ablate virus infectivity. Interestingly, two mutations that do not prevent binding can also impair infectivity.

Amino Acid Sequence↗

pet, a small sequence distal to the pregenome cap site, is required for expression of the duck hepatitis B virus pregenome.

We have found that transcription of the pregenome of an avian hepadnavirus, duck hepatitis B virus (DHBV), is dependent on the presence of a small element in the 5' transcribed region of the pregenome-encoding sequence. This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. The requirement for pet depends on the presence in the transcription unit of a region of the DHBV genome located upstream of the envelope promoters, which specifically suppresses transcription of templates lacking pet. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA.

Animals↗

Two regions of an avian hepadnavirus RNA pregenome are required in cis for encapsidation.

We have constructed a series of deletion mutants spanning the genome of duck hepatitis B virus in order to determine which regions of the viral genome are required in cis for packaging of the pregenome into capsid particles. Deletion of sequences within either of two nonadjacent regions prevented replication of the mutant viral genomes expressed in a permissive avian hepatoma cell line in the presence of functionally active viral core and P proteins. Extraction of RNA from cells transfected with these replication-defective mutants showed that the mutants retained the capacity to be transcribed into a pregenomic-size viral RNA, but that these RNA species were not packaged into viral capsids. The two regions defined by these deletions are located 36 to 126 (region I) and 1046 to 1214 (region II) nucleotides downstream of the 5' end of the pregenome and contain sequences which are required in cis for encapsidation of the duck hepatitis B virus pregenome.

Base Sequence↗

Phosphorylation of the duck hepatitis B virus capsid protein associated with conformational changes in the C terminus.

The capsid protein of duck hepatitis B virus (DHBV) is phosphorylated at multiple sites during viral infection. A cluster of sites is located near the C terminus of the 262-amino-acid protein. We have used site-directed mutagenesis to show that three serines and one threonine serve as phosphate acceptor amino acids in the C terminus. An additional six potential phosphate acceptor sites in this region were apparently not utilized. Each serine or threonine that served as a phosphate acceptor was adjacent to a downstream proline, while all six serines that were not acceptors for phosphate residues lacked adjacent downstream prolines. Mutation of the downstream proline to glycine at each site had the same effect as mutating the serine itself, suggesting an SP or TP motif as an essential feature for capsid protein phosphorylation. Phosphorylation at these four sites resulted in complex shifts in electrophoretic mobility in sodium dodecyl sulfate gels of the capsid protein or of a C-terminal peptide containing the phosphorylated sites, suggesting that specific conformations of the C terminus are associated with different combinations of phosphorylated serines. We speculate that distinct functions of the C terminus may be associated with different phosphorylated domains on the intact capsid.

Amino Acid Sequence↗

Multiple functions of capsid protein phosphorylation in duck hepatitis B virus replication.

We have investigated the role of phosphorylation of the capsid protein of the avian hepadnavirus duck hepatitis B virus in viral replication. We found previously that three serines and one threonine in the C-terminal 24 amino acids of the capsid protein serve as phosphorylation sites and that the pattern of phosphorylation at these sites in intracellular viral capsids is complex. In this study, we present evidence that the phosphorylation state of three of these residues affects distinct steps in viral replication. By substituting these residues with alanine in order to mimic serine, or with aspartic acid in order to mimic phosphoserine, and assaying the effects of these substitutions on various steps in virus replication, we were able to make the following inferences. (i) The presence of phosphoserines at residues 245 and 259 stimulates DNA synthesis within viral nucleocapsids. (ii) The absence of phosphoserine at residue 257 and at residues 257 and 259 stimulates covalently closed circular DNA synthesis and virus production, respectively. (iii) The presence of phosphoserine at position 259 is required for initiation of infection. The results implied that both phosphorylated and nonphosphorylated capsid proteins were necessary for a nucleocapsid particle to carry out all its functions in virus replication, explaining why differential phosphorylation of the capsid protein occurs in hepadnaviruses. Whether these differentially phosphorylated proteins coexist on the same nucleocapsid, or whether the nucleocapsid acquires sequential functions through selective phosphorylation and dephosphorylation, is discussed.

Alanine↗

Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus.

We have used linker scanning and site-directed mutagenesis in an attempt to distinguish among the known functions of the duck hepatitis B virus large envelope protein, p36. We found that linker-encoded amino acid substitutions in at least one region of the pre-S envelope protein p36 produced defects in both the production of enveloped virus and the regulation of covalently closed circular DNA (cccDNA) synthesis. Most linker substitutions, typically in the 5' two-thirds of the pre-S region of the p36 gene did not affect either cccDNA regulation or enveloped virus production but did destroy the infection competence of the enveloped particles produced. Single amino acid substitutions of residues 128 and 131 demonstrated a similar correlation between defects in the ability of p36 to support enveloped virus production and to control cccDNA levels. We concluded from these studies that virus production and cccDNA regulation probably require a common activity of p36.

Amino Acid Sequence↗

Construction of avian hepadnavirus variants with enhanced replication and cytopathicity in primary hepatocytes.

Hepadnaviruses cause persistent noncytopathic infections of hepatocytes in humans and other animals. Virus replication depends on the pool of viral covalently closed circular DNA (cccDNA) molecules, which serve as transcriptional templates in the nuclei of infected cells. The size of this pool of cccDNA molecules is regulated by the ability of the large envelope protein of the virus to direct newly synthesized viral DNAs into a pathway for viral secretion and thereby inhibit their utilization for viral cccDNA synthesis. In this study, we showed that single amino acid changes in the large envelope protein could cause profound changes in cccDNA levels in transfected permissive cells or in infected cultured hepatocytes. While defects in cccDNA regulation were accompanied by a decrease of enveloped virus production in transfected cells, primary hepatocytes infected by such mutant viruses transiently produced wild-type or higher levels of enveloped virus. Moreover, high levels of cccDNA were always associated with cytopathic effects in the infected hepatocytes. The results demonstrate that the large envelope protein promotes persistent noncytopathic infection of hepatocytes by acting as an overall repressor of virus replication.

Animals↗