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Biomedical subjects

L Kuhn

Publications and source records attributed to L Kuhn.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prevalence of visible disruption of cervical epithelium and cervical ectopy in African women using Depo-Provera.

Associations between Depo-Provera (injectable, progesterone-only contraceptive) use and visible disruption of cervical epithelium and cervical ectopy were investigated using data collected as part of a cervical cancer screening study in periurban Cape Town, South Africa. Women were interviewed about their contraceptive use, and underwent a gynecologic examination that included two 35-mm photographs of the cervix after application of 5% acetic acid. Photographs of 723 subjects were reviewed (blind to clinical information and using systematic criteria developed before review) for evidence of atrophy and epithelial disruption, including inflammation and ulceration. The percentage of the cervix covered with columnar epithelium (ectopy) was also estimated from the photographs. A random sample of 85 photographs was reviewed again for reliability. A total of 121 current users of Depo-Provera were no more likely to have evidence of epithelial disruption (38%) than 574 nonusers (39%), odds ratio (OR) = 1.37, 95% CI: 0.89-2.11 adjusting for age and parity. The prevalence of significant ectopy (columnar epithelium covering > 10% of the cervix) was also no different among current Depo-Provera users (OR = 1.22, 95% CI: 0.80-1.86 adjusting for age and parity). Reliability of visual scoring of epithelial disruption and ectopy was excellent (kappa = 0.8). Although the underlying prevalence of visible disruption of cervical epithelium was very high, current use of Depo-Provera was not associated with increased prevalence of visible disruption of the cervical epithelium or with ectopy in this sample of African women.

Adult↗
PubMed1999

Distinct risk factors for intrauterine and intrapartum human immunodeficiency virus transmission and consequences for disease progression in infected children. Perinatal AIDS Collaborative Transmission Study.

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Anti-HIV Agents↗
PubMed1999

Human immunodeficiency virus infection and female lower genital tract malignancy.

The risk of lower genital tract neoplasia is increased in women infected with HIV. This has been best demonstrated in cervical squamous intraepithelial lesions, but has also been observed in vulvar and perianal intraepithelial lesions in some studies. Alterations in the prevalence and natural history of human papillomavirus infections of the lower genital tract appear to account for much of the increase. HIV-infected women are approximately four times more likely to be infected with human papillomavirus (including infection with high oncogenic risk human papillomavirus types) than are HIV-uninfected women, and these infections are more likely to be persistent. Human papilomavirus-associated lesions may be more difficult to treat in HIV-infected women. These data highlight the need to develop effective cervical cancer prevention programs for HIV-infected women.

Anus Neoplasms↗
PubMed1998

Long-term survival of children with human immunodeficiency virus infection in New York City: estimates from population-based surveillance data.

The life expectancy of children with human immunodeficiency virus (HIV) infection acquired through mother-to-child transmission has important clinical and public health significance. Several sources of population-based surveillance data from New York City, covering 1982 through the end of 1994, were combined to estimate long-term survival of HIV-infected children and age-specific prevalence. HIV incidence among newborns was estimated by applying expected transmission rates to seroprevalence surveys of parturient women and by using back-calculation methods. HIV prevalence in childhood was based on cumulative HIV incidence and cumulative mortality, adjusting for underreporting of death and background causes of death. A modified actuarial method was developed to estimate survival of infected children. At the beginning of 1995, between 1,945 and 3,323 children less than age 13 years were estimated to be living with HIV infection acquired through mother-to-child transmission in New York City. Between 36% and 61% of these infected children were estimated to survive to age 13 years (median survival, 8.6 years to >13 years). A substantial proportion of infected children will survive to adolescence. Thus, it is important that their educational, medical, and other needs be considered. These methods may be useful in other areas in which HIV seroprevalence data among childbearing women and HIV mortality statistics are available.

Adolescent↗
PubMed1997

Human papillomavirus infection in women infected with the human immunodeficiency virus.

BACKGROUND: Among women infected with the human immunodeficiency virus (HIV), there is a high prevalence of human papillomavirus (HPV) infections. However, little is known about the natural history of HPV infections in HIV-seropositive women, and persistent HPV infections may explain the increased risk of cervical squamous intraepithelial lesions and invasive cervical cancer in HIV-seropositive women. METHODS: A total of 220 HIV-seropositive and 231 HIV-seronegative women in the New York City area were evaluated at two or more semiannual gynecologic examinations that included a Pap test, a test for HPV DNA, and colposcopy. RESULTS: HPV DNA was detected at the initial examination in 56 percent of the HIV-seropositive and 31 percent of the HIV-seronegative women. After four examinations, the cumulative prevalence of HPV infection was 83 percent in the seropositive women and 62 percent in the seronegative women (P<0.001). Persistent HPV infections were found in 24 percent of the seropositive women but in only 4 percent of the seronegative women (P<0.001). Twenty percent of the seropositive women and 3 percent of the seronegative women had persistent infections with HPV-16-associated viral types (16, 31, 33, 35, or 58) or HPV-18-associated types (18 or 45) (P<0.001), which are most strongly associated with cervical cancer. The detection of HPV DNA in women with previously negative tests was not associated with sexual activity during the interval since the preceding examination. CONCLUSIONS: HIV-seropositive women have a high rate of persistent HPV infections with the types of HPV that are strongly associated with the development of high-grade squamous intraepithelial lesions and invasive cervical cancer. These persistent infections may explain the increased incidence of squamous intraepithelial lesions in HIV-seropositive women.

AIDS-Related Opportunistic Infections↗
PubMed1997

Complex regulation of transferrin receptors during erythropoietin-induced differentiation of J2E erythroid cells--elevated transcription and mRNA stabilisation produce only a modest rise in protein content.

The regulation of transferrin-receptor synthesis was studied in J2E erythroid cells induced to differentiate with erythropoietin. Nuclear run-on assays demonstrated that transcription of the transferrin-receptor gene rose markedly after erythropoietin treatment. In addition, transferrin-receptor mRNA was stabilised and this was associated with an increase in the activity of the RNA-binding protein IRP (iron regulatory protein). As a result of increased transcription and mRNA stabilisation, steady-state RNA levels increased 10-20-fold. However, despite these large increases in mRNA, translation only doubled; consequently, modest increases in total protein and surface transferrin receptors were observed. Moreover, this rise in transferrin receptors was transient, and correlated with a burst of proliferation shortly after erythropoietin treatment. The expected inverse relationship between transferrin receptors and ferritin did not occur during J2E maturation as translation of both ferritin subunits increased when transferrin-receptor mRNA levels rose. Analysis of mutant J2E clones incapable of synthesising haemoglobin revealed that surface transferrin-receptor levels were only 15-25% that of the parental erythroid line. We propose that the surface expression of transferrin receptors in J2E cells is governed by three factors: basal levels essential for normal growth in culture; elevated levels needed for haemoglobin synthesis; and a transient erythropoietin-induced increase that is required for the final burst of proliferation. It was concluded that the regulation of transferrin-receptor production in erythropoietin-stimulated J2E cells is complex and that there are several sites of control.

Animals↗
PubMed1997

Neutrophils as a source of putative restriction proteases: degradation of mammalian and yeast proteins monitored by two-dimensional gel electrophoresis.

We have compared the ability of intact neutrophils to degrade a complex substrate of proteins from mammalian and yeast origin. The substrate was obtained by biosynthetic labeling, and subsequent lysis of K562 cells (leukemic cell line) and of yeast culture. The mammalian substrate consisted of 619 and the yeast substrate of 185 different polypeptides, as visualized and represented on two-dimensional gel patterns. Upon incubation of the mammalian substrate with neutrophils, the bulk of spots disappeared so rapidly that after 240 min of incubation only 21 spots were detectable. Just one spot remained unaltered in its intensity throughout the whole period of incubation. About 440 spots reveal a t1/2 shorter than 8 min. Yeast substrate is represented by a smaller number of the starting polypeptides (185) from which 55 spots "survive" the neutrophil treatment. About 30 spots have a t1/2 shorter than 8 min. We conclude that neutrophils are equipped with a potent proteolytic apparatus, and this is capable of eliminating various proteins in a highly efficient manner. The system is much less effective in eliminating proteins from distant species, like yeast. Although the cells governing and regulating the immune system are clearly of lymphoid origin, it might well be that the preimmune task of eliminating self antigens in a manner as predicted in the restriction protease hypothesis is performed by neutrophils.

Animals↗
PubMed1997

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

Birth Weight↗
PubMed1997

Analysis of a randomly assorted cDNA library from BW 5147 lymphoid cells. Frequency estimates based on computer aided concatenation matching of 2D gel polypeptide products.

A cDNA library was divided into 291 sectors of low complexity, 800-1000 recombinant phage plaques per sector. Aliquots of DNA from sectors prepared from high titer phage were subjected to in vitro transcription using T7 polymerase and thereafter RNA was translated in a cell-free rabbit reticulocyte system in the presence of [35S] methionine. The resulting polypeptides were separated by 2D gel electrophoresis. Radiofluorographs of the gels prepared from 10 sectors were subjected to scanning and image analysis. A multilevel spot matching procedure was employed allowing us to recognise spot occurrence in the 10 sectors. The number of detected polypeptide spots per sector varied between 147 and 325. Overall, 1082 different spots were counted totalling 1983 spots considering multiple entries. The distribution of the spots and the frequency distribution of the RNA population among the 10 sectors are shown. The highest detected frequency is 10(-2), while one half of the RNA molecular species are present at a frequency of 10(-3) or lower.

Animals↗
PubMed1997

Isolation and characterization of the mycobacterial phagosome: segregation from the endosomal/lysosomal pathway.

Mycobacteria have the ability to persist within host phagocytes, and their success as intracellular pathogens is thought to be related to the ability to modify their intracellular environment. After entry into phagocytes, mycobacteria-containing phagosomes acquire markers for the endosomal pathway, but do not fuse with lysosomes. The molecular machinery that is involved in the entry and survival of mycobacteria in host cells is poorly characterized. Here we describe the use of organelle electrophoresis to study the uptake of Mycobacterium bovis bacille Calmette Guerin (BCG) into murine macrophages. We demonstrate that live, but not dead, mycobacteria occupy a phagosome that can be physically separated from endosomal/lysosomal compartments. Biochemical analysis of purified mycobacterial phagosomes revealed the absence of endosomal/lysosomal markers LAMP-1 and beta-hexosaminidase. Combining subcellular fractionation with two-dimensional gel electrophoresis, we found that a set of host proteins was present in phagosomes that were absent from endosomal/lysosomal compartments. The residence of mycobacteria in compartments outside the endosomal/lysosomal system may explain their persistence inside host cells and their sequestration from immune recognition. Furthermore, the approach described here may contribute to an improved understanding of the molecular mechanisms that determine the intracellular fate of mycobacteria during infection.

Animals↗
PubMed1997

Infant survival, HIV infection, and feeding alternatives in less-developed countries.

OBJECTIVES: This study examines, in the context of the human immunodeficiency virus (HIV) epidemic, the effects of optimal breast-feeding, complete avoidance of breast-feeding, and early cessation of breast-feeding. METHODS: The three categories of breast-feeding were weighed in terms of HIV transmission and infant mortality. Estimates of the frequency of adverse outcomes were obtained by simulation. RESULTS: Avoidance of all breast-feeding by the whole population always produces the worst outcome. The lowest frequency of adverse outcomes occurs if no HIV-seropositive women breast-feed and all seronegative women breast-feed optimally, given infant mortality rates below 100 per 1000 and relative risks of dying set at 2.5 for non-breast-fed compared with optimally breast-fed infants. For known HIV-seropositive mothers, fewer adverse outcomes result from early cessation than from prolonged breast-feeding if the hazard of HIV transmission through breast-feeding after 3 months is 7% or more, even at high mortality rates, given relative risks of dying set at 1.5 for early cessation compared with optimal duration of breast-feeding. CONCLUSIONS: The risk of HIV transmission through breast-feeding at various ages needs to be more precisely quantified. The grave issues that may accompany a possible decline in breast-feeding in the less developed world demand evaluation.

Adult↗
PubMed1996

Cesarean deliveries and maternal-infant HIV transmission: results from a prospective study in South Africa.

Data from a prospective study undertaken at an urban hospital in Durban, South Africa, were used to investigate associations between maternal-infant HIV transmission, mode of delivery, and specific circumstances of cesarean deliveries. A total of 141 children of HIV-infected women were followed until the children were 15 months of age to determine their HIV status. supplementary data were collected from obstetric records, masked to the HIV status of the children. In this African and predominantly breast-fed population, infants delivered vaginally were more likely to be infected (39.8% infected) than were infants delivered by cesarean section [22.9% infected; odds ratio (OR), 0.45; 95% confidence interval (CI), 0.20-0.99]. There were no significant differences between cesarean deliveries undertaken following prior rupture of membranes and those undertaken with membranes intact, but numbers for this comparison were small. Singleton cesarean deliveries without concurrent obstetric complications had lower rates of transmission than did vaginal deliveries (OR, 0.20; 95% CI, 0.04-0.94). These results suggest that certain intrapartum events may modify the risk of HIV transmission and highlight the importance of collecting more detailed intrapartum information in order to clarify the route by which mode of delivery may be associated with maternal-infant HIV transmission.

Breast Feeding↗
PubMed1996

Initial binding of the elongation factor Tu.GTP.aminoacyl-tRNA complex preceding codon recognition on the ribosome.

The first step in the sequence of interactions between the ribosome and the complex of elongation factor Tu (EF-Tu), GTP, and aminoacyl-tRNA, which eventually leads to A site-bound aminoacyl-tRNA, is the codon-independent formation of an initial complex. We have characterized the initial binding and the resulting complex by time-resolved (stopped-flow) and steady-state fluorescence measurements using several fluorescent tRNA derivatives. The complex is labile, with rate constants of 6 x 10(7) M-1 s-1 and 24 s-1 (20 degrees C, 10 mM Mg2+) for binding and dissociation, respectively. Both thermodynamic and activation parameters of initial binding were determined, and five Mg2+ ions were estimated to participate in the interaction. While a cognate ternary complex proceeds form initial binding through codon recognition to rapid GTP hydrolysis, the rate constant of GTP hydrolysis in the non-cognate complex is 4 orders of magnitude lower, despite the rapid formation of the initial complex in both cases. Hence, the ribosome-induced GTP hydrolysis by EF-Tu is strongly affected by the presence of the tRNA. This suggests that codon-anticodon recognition, which takes place after the formation of the initial binding complex, provides a specific signal that triggers fast GTP hydrolysis by EF-Tu on the ribosome.

Codon↗
PubMed1996

Epidemiology and prevention of severe assault and gun injuries to children in an urban community.

OBJECTIVES: To describe the epidemiology of severe assault and gun injuries to children in an urban population and consider the impact of a comprehensive injury prevention program. MATERIALS AND METHODS: Pediatric injury deaths and hospital admissions for Northern Manhattan (1983-1992) were linked to census counts to compute incidence. Poisson regression was used to compare trends in incidence of assault and gun injuries before and during a community-wide pediatric injury prevention program in Central Harlem. MAIN RESULTS: The incidence of severe nonfatal assault injury was 60.94/100,000/year, 10 times the fatality rate. The incidence of all gun injuries was 31.13. In adolescence, guns were the leading cause of both fatal and severe nonfatal assault injury, and were the most lethal method of assault (case-fatality = 18.5% for gun vs. 1.2% for all non-gun assault injury). Rates of assault and gun injuries declined by nearly 50% in the intervention community, while they increased in a neighboring community. CONCLUSIONS: Comprehensive interventions may be effective in curbing the incidence of severe assault injuries to urban youth. Further controlled evaluations are needed to confirm the effectiveness of programs such as this and to better understand the prevention of violent injuries.

Adolescent↗
PubMed1995

Codon-dependent conformational change of elongation factor Tu preceding GTP hydrolysis on the ribosome.

The mechanisms by which elongation factor Tu (EF-Tu) promotes the binding of aminoacyl-tRNA to the A site of the ribosome and, in particular, how GTP hydrolysis by EF-Tu is triggered on the ribosome, are not understood. We report steady-state and time-resolved fluorescence measurements, performed in the Escherichia coli system, in which the interaction of the complex EF-Tu.GTP.Phe-tRNAPhe with the ribosomal A site is monitored by the fluorescence changes of either mant-dGTP [3'-O-(N-methylanthraniloyl)-2-deoxyguanosine triphosphate], replacing GTP in the complex, or of wybutine in the anticodon loop of the tRNA. Additionally, GTP hydrolysis is measured by the quench-flow technique. We find that codon-anticodon interaction induces a rapid rearrangement within the G domain of EF-Tu around the bound nucleotide, which is followed by GTP hydrolysis at an approximately 1.5-fold lower rate. In the presence of kirromycin, the activated conformation of EF-Tu appears to be frozen. The steps following GTP hydrolysis--the switch of EF-Tu to the GDP-bound conformation, the release of aminoacyl-tRNA from EF-Tu to the A site, and the dissociation of EF-Tu-GDP from the ribosome--which are altogether suppressed by kirromycin, are not distinguished kinetically. The results suggest that codon recognition by the ternary complex on the ribosome initiates a series of structural rearrangements resulting in a conformational change of EF-Tu, possibly involving the effector region, which, in turn, triggers GTP hydrolysis.

Anticodon↗
PubMed1995

Mother-to-infant HIV transmission: timing, risk factors and prevention.

Identifying when--during pregnancy, delivery or the postnatal period--transmission of human immunodeficiency virus (HIV) from mother to infant usually takes place is critical to the development of methods to prevent maternal-infant transmission. Evidence is reviewed in this paper as to whether transmission occurs prepartum (early or late in gestation), intrapartum, or postpartum with breast feeding. Evidence in support of the notion of prepartum transmission has come from isolation of HIV from aborted fetal organs, comparison of maternal-child viral genotypes and study of neonatal cell-mediated immune responses. Evidence against prepartum transmission is that fewer than half of the children later known to be HIV-infected can be identified by virological tests carried out close to birth. A reduced rate of transmission in infants delivered by Caesarean section, and a reduced risk of transmission to second-born twins delivered vaginally, offers support to the view that intrapartum factors influence the risk of HIV transmission. Transmission through breast feeding can occur if a mother is infected postpartum and seems to pose some additional risk if she is already infected at parturition. The risk of infection increases with the stage of maternal HIV disease, but specific immunological, clinical and viral characteristics need to be investigated further. A clinical trial of zidovudine, used during late pregnancy and delivery and given to the infant at birth, has reported a significant reduction in transmission. Primary prevention of HIV infection in women remains a principal priority.

Female↗