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Biomedical subjects

E Morse

Publications and source records attributed to E Morse.

At least 19 recordsLinked to original sources
PubMed2001

Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants.

We have shown that the HIV-1 laboratory strain NL4-3 that contains P236L [a reverse transcriptase mutation conferring resistance to the nonnucleoside reverse transcriptase inhibitor (NRTI) delavirdine] replicates more slowly than wild-type NL4-3. Other NNRTI-resistance mutations, such as K103N and Y181C, do not reduce the replication capacity of NL4-3 as much as P236L and develop more frequently in HIV-1 isolates from patients failing delavirdine. However, a minority of patients on delavirdine therapy still have isolates with P236L. We postulated that reverse transcriptase (RT) sequences from these patient isolates contain other mutations that compensate for the adverse effect of P236L. To test this hypothesis, we created 15 chimeric NL4-3 isolates that contained delavirdine-resistant RT sequences derived from eight patient isolates and characterized their replication kinetics. Nine of 10 patient-derived clones containing P236L replicated as slowly as NL4-3 with P236L. In contrast, three of five clones that did not have P236L (but had either K103N or Y181C) replicated significantly better than NL4-3 with P236L. Thus, the majority of patients who acquire P236L during delavirdine therapy do not have RT mutations that compensate for the replication defect conferred by P236L. We hypothesize that HIV-1 isolates with P236L may have a compensatory mutation outside RT. Alternatively, variants of HIV-1 with reduced replication fitness may be selected during antiretroviral therapy, suggesting that stochastic events rather than viral replication fitness may determine which drug-resistant mutants emerge early during antiretroviral failure. In some isolates, it appears that the background RT sequence can contribute significantly to the replication fitness of drug-resistant HIV-1 variants.

Anti-HIV Agents↗
PubMed2001

A sequence-ready map of the human chromosome 1q telomere.

A 260-kb half-YAC clone derived from human chromosome 1q was mapped at high resolution using cosmid subclone fingerprint analysis and was integrated with overlapping clones from the telomeric end of a separately derived 1q44 BAC contig to create a sequence-ready map extending to the molecular telomere of 1q. Analysis of 100 kb of sample sequences from across the 260-kb region encompassed by the half-YAC revealed the presence of EST sequence matches corresponding to 12 separate Unigene clusters and to 12 separate unclustered EST sequences. Low-copy subtelomeric repeats typical of many human telomere regions are present within the distal-most 30 kb of 1q. The previously isolated and radiation hybrid-mapped markers Bda84F03, 1QTEL019, and WI11861 localized at distances approximately 32, 88, and 99 kb, respectively, from the 1q terminus. This sequence-ready map permits high-resolution integration of genetic maps with the DNA sequences directly adjacent to the tip of human chromosome 1q and will enable telomeric closure of the human chromosome 1q DNA reference sequence by connecting the molecular 1q telomere to an internal BAC contig.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Integration of telomere sequences with the draft human genome sequence.

Telomeres are the ends of linear eukaryotic chromosomes. To ensure that no large stretches of uncharacterized DNA remain between the ends of the human working draft sequence and the ends of each chromosome, we would need to connect the sequences of the telomeres to the working draft sequence. But telomeres have an unusual DNA sequence composition and organization that makes them particularly difficult to isolate and analyse. Here we use specialized linear yeast artificial chromosome clones, each carrying a large telomere-terminal fragment of human DNA, to integrate most human telomeres with the working draft sequence. Subtelomeric sequence structure appears to vary widely, mainly as a result of large differences in subtelomeric repeat sequence abundance and organization at individual telomeres. Many subtelomeric regions appear to be gene-rich, matching both known and unknown expressed genes. This indicates that human subtelomeric regions are not simply buffers of nonfunctional 'junk DNA' next to the molecular telomere, but are instead functional parts of the expressed genome.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Father-child contact in inner-city African American families with maternal HIV infection.

This study examines father-child contact in inner-city African American families with maternal HIV infection. Participants were 246 African American women, 40% of whom are infected with HIV, and one of their non-infected children. Children from non-infected families were more likely to have fathers who are alive and who are living in the home. In addition, regardless of whether or not the father lived in the home, these children had more frequent father contact than children from families with maternal HIV infection. Explanations and implications of the findings are discussed.

Adolescent↗
PubMed2000

Child resiliency in inner-city families affected by HIV: the role of family variables.

This study examined the role of family variables in child resiliency within a sample of African-American, inner-city children whose mothers are HIV-infected. Variables from three dimensions of the family were included: family structural variables, maternal variables, and mother-child (parenting) variables. The participants were 82 children between the ages of 6 and 11 and their HIV-infected mothers. Correlational analyses indicated that resiliency was associated only with three parenting variables: parent-child relationship, parental monitoring, and parental structure in the home. Hierarchical regression analyses indicated a multiplicative relationship between parental monitoring and parent-child relationship and between parental monitoring and parental structure in the home, suggesting that parenting variables potentiate each other. Clinical implications of the findings are considered.

Adaptation, Psychological↗
PubMed1999

Coping strategies and behavior problems of urban African-American children: concurrent and longitudinal relationships.

The development and correlates of 82 inner-city African-American children's coping strategies were examined across three years. Results indicated no change in the mean frequency of self-reported coping strategies over the three years, and a significant correlation of emotion-focused strategies with increased self- and mother-reported behavior problems. Child-reported externalizing problems (and, to a lesser degree, internalizing problems) predicted changes in coping strategies across assessments.

Adaptation, Psychological↗
PubMed1999

Orphans of the AIDS epidemic in the United States: transition-related characteristics and psychosocial adjustment at 6 months after mother's death.

This study has two purposes: (1) to describe the characteristics related to the transition to orphanhood for children whose mothers die from AIDS and (2) to examine the psychosocial adjustment of these children at six months following maternal death. Twenty orphans and a control sample of 40 children from the same neighbourhoods, as well as their mothers or care-givers, served as participants. Two assessments occurred: (1) prior to the death of the mother in the orphan group and (2) six months after her death. The results indicated that relatives, particularly maternal grandparents, became the new care-giver of the orphans, no more than one residential move had occurred following the mother's death, and the new care-givers were providing a stable home environment. Child psychosocial adjustment did not change following maternal death.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Women who are HIV infected: the role of religious activity in psychosocial adjustment.

The role of religious activity in the psychosocial adjustment of 205 inner-city African-American women, one-half of whom are HIV infected, was examined. Those who were HIV infected reported praying more but viewed prayer as less effective in coping with a chronic illness. Frequency of prayer predicted optimism about the future, whereas religious activity was not related to current depressive symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Traumatic stress in HIV-infected women.

This study assesses the prevalence of specific traumatic stressors that meet criterion A for the Diagnostic and Statistical Manual of Mental Disorders' (DSM-IV) diagnosis of posttraumatic stress disorder (PTSD) and symptoms of PTSD in a representative sample of HIV-infected women. The study also assesses the impact of these stressors and symptoms on the clinical progression of HIV infection. The Life Stressor Checklist and the Impact of Events Scale-Revised were administered via interview to 67 Africa-American women beyond the initial stages of HIV infection. The ratio of CD4 t-cells to CD8 t-cells were abstracted from medical records at dates that approximated psychological interviews and were examined at two points in time 12 to 14 months apart. The prevalence of traumatic stressors and PTSD symptoms were high among HIV-infected women. Traumatic stressors were significantly associated with a lower CD4 to CD8 ratio at the 1-year follow-up. Among women who reported a traumatic event, those who also met criteria for PTSD evidenced a lower CD4 to CD8 ratio at the follow-up assessment. The study concludes that prevention and treatment efforts targeted at HIV-infected women must take into account traumatic stressors and PTSD symptoms and their potential impact on the course of the disease.

Adolescent↗
PubMed1998

The Family Health Project: psychosocial adjustment of children whose mothers are HIV infected.

The psychosocial adjustment of 87 inner-city African American children 6-11 years old whose mothers were HIV infected was compared with that of 149 children from a similar sociodemographic background whose mothers did not report being HIV infected. Children were not identified as being HIV infected. Mother reports, child reports, and standardized reading achievement scores were used to assess 4 domains of adjustment: externalizing problems, internalizing problems, cognitive competence, and prosocial competence. The results indicated that, on average, children from both groups had elevated levels of behavior problem scores and low reading achievement scores when compared with national averages. Relative to children whose mothers were not infected, those whose mothers were HIV infected were reported to have more difficulties in all domains of psychosocial adjustment. Potential family processes that may explain the findings are discussed.

Achievement↗
PubMed1996

Mechanism of clearance and transfer of dipeptides by perfused human placenta.

Glycylglutamine (Gly-Gln) is stable source of glutamine for parenteral nutrition. In the present study we have investigated whether this dipeptide is transferred intact across the human placenta. Although after 90 min of placental perfusion there was almost complete disappearance of Gly-Gln (100 microM) from the maternal compartment, only a small concentration of this dipeptide (< 6 microM) appeared in the fetal compartment. To investigate whether this transfer was due to transcellular transport, brush-border membrane vesicles of the human placenta were probed with [3H]Gly-Gln, which showed no uptake. To investigate whether hydrolysis was the mechanism of disappearance of Gly-Gln, the perfusion study was repeated with glycylsarcosine (Gly-Sar), which is resistant to hydrolysis. In sharp contrast to Gly-Gln, after 90 min of perfusion nearly 80% of Gly-Sar remained in the perfusate (half-life of 24 vs. 235 min). The rest of the Gly-Sar was recovered intact in the fetal compartment. The addition of Gly-Gln to the maternal compartment increased the accumulation of glycine, but not glutamine, in both the maternal and fetal compartments. In conclusion, our data suggest that 1) the mechanism of clearance of Gly-Gln by perfused human placenta is largely hydrolysis, whereas that of Gly-Sar is largely passive diffusion, and 2) the placenta has a greater preference for glutamine than for glycine.

Dipeptides↗
PubMed1986

The motivation to use drugs: a psychobiological analysis of urges.

Traditionally, theories of addiction have stressed that drug urges are characterized by dysphoria, occur in response to decreasing levels of drug or drug effect, and are associated with withdrawal symptoms/signs or drug-antagonistic responses arising from a homeostatic mechanism. However, recent research has shown that urges, drug self-administration, and relapse all occur concomitant with both positive and negative affect, rising and falling levels of drug, and with drug-agonistic responses, as well as antagonistic/withdrawal responses. In keeping with recent theorizing about motivation and emotions, we believe that affective responding provides a readout of the motivational status of an organism (e.g., Buck, 1985). We conceive of urges as affects, whose activation mediates drug pursuit and self-administration. Moreover, we believe that affects are represented in neural networks comprising information on affect-relevant stimuli, responses, and meaning/expectancy. We believe that there are two types of urge networks. One, a "positive-affect" network, is activated, associatively and nonassociatively, by appetitive stimuli, especially appetitive drug actions that activate "GO" motivational incentive systems. Activation of this network is characterized by positive affect, drug isodirectional responding, attentional focus on a dominant response, and enhanced pursuit of appetitive stimuli--especially the drug. The operating characteristics of the positive-affect network, and the associated motivational systems, result in a drug's instating a positive feedback loop. Appetitive drug actions increase the likelihood of the pursuit of appetitive stimuli, and additional drug constitutes a prepotent candidate from among the available appetitive stimuli. This positive feedback loop may account in part for cardinal features of addiction: for example, the great relapse likelihood once any drug is sampled, the attainment of very high blood levels of a drug, and the pursuit of adjunctive appetitive stimuli while using a drug. The second type of urge network we have labeled a "negative-affect" network, and we believe it is activated, associatively and nonassociatively, by inappetitive stimuli or consequences (punishment, signals of punishment, frustrating lack of reward, etc.) and by withdrawal and signals of withdrawal (e.g., drug cues, which during the course of addiction are associated with both direct drug effects and withdrawal). Activation of the network is characterized by withdrawal symptoms and signs, negative affect, and drug seeking.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Psychological↗
PubMed1981

Dysmenorrhea induced by autologous transfusion.

A circulating factor capable of inducing symptoms of dysmenorrhea has been demonstrated in 10 women by collecting plasma during periods of dysmenorrhea and infusing it during asymptomatic intervals. Typical symptoms of abdominal pain occurred in 8 of 12 women who received a plasma infusion that had been drawn at the time symptoms were present. Plasma drawn at the time of no symptoms, when given to 10 women, produced no abdominal pain (P less than .01). Combinations of pain and/or emotional irritability were found in 11 of 12 women after symptomatic units were infused and in only 2 of 10 women after asymptomatic units were infused (P less than .001). The uterus need not be involved, as 7 of 10 patients had a hysterectomy prior to the infusions. It is suggested that a circulating factor may activate prostaglandin synthesis, which in turn may stimulate the neuronal system, thus causing symptoms.

Abdomen↗
PubMedDate not supplied

Disclosing HIV status: are mothers telling their children?

OBJECTIVE: Mothers living with HIV face a complex set of child-rearing decisions, often within the context of many competing stressors. One difficult decision for HIV-infected mothers is whether to disclose their HIV status to their children. The purpose of this study is to provide information to HIV-affected families and the professionals working with them as they approach disclosure-related decisions. METHODS: Eighty-seven HIV-infected African American mothers and one of their children who was not HIV-infected were separately interviewed on two occasions. Mothers reported whether they disclosed their HIV status to the child and provided their assessment of the child's functioning. Children also completed an assessment of their functioning. RESULTS: Results revealed that less than one-third of mothers disclosed their HIV status to their children. Disclosure was associated with mother's income level and perceived severity of physical symptoms. In addition, children disclosed to were more often older and female. Contrary to expectation, disclosure was not related to child functioning. CONCLUSIONS: Professionals should note the low rate of disclosure among these families. In the absence of conclusive data regarding impact on child functioning, professionals must remain aware of the complexity of disclosure-related decisions when working with HIV-affected families, particularly in terms of the family and cultural milieu within which families operate.

Adult↗
PubMedDate not supplied

Adoptive transfer of activated human autologous macrophages results in regression of transplanted human melanoma cells in SCID mice.

The potential anti-tumor activity of human macrophages, grown in macrophage colony stimulating factor (M-CSF), was examined in mice homozygous for the mutation severe combined immune deficiency (scid) bearing xenografts of autologous human melanoma. Injection of scid mice, bearing subcutaneous melanoma xenografts, with the cultured macrophages or with the macrophage culture supernatant, once or repeatedly, resulted in partial to complete regression of tumors. Since a large number of such macrophages (greater than 1 x 10(9)) could be grown in vitro for repeated injection, the scid-human chimera can serve as an in vivo model to examine the role of human macrophages in tumor immunity and to explore the potential of the in vitro cultured macrophages in the therapy of cancer.

Animals↗