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Biomedical subjects

K E Nelson

Publications and source records attributed to K E Nelson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Status of genome projects for nonpathogenic bacteria and archaea.

Since the first microbial genome was sequenced in 1995, 30 others have been completed and an additional 99 are known to be in progress. Although the early emphasis of microbial genomics was on human pathogens for obvious reasons, a significant number of sequencing projects have focused on nonpathogenic organisms, beginning with the release of the complete genome sequence of the archaeon Methanococcus jannaschii in 1996. The past 18 months have seen the completion of the genomes of several unusual organisms, including Thermotoga maritima, whose genome reveals extensive potential lateral transfer with archaea; Deinococcus radiodurans, the most radiation-resistant microorganism known; and Aeropyrum pernix, the first Crenarchaeota to be completely sequenced. Although the functional characterization of genomic data is still in its initial stages, it is likely that microbial genomics will have a significant impact on environmental, food, and industrial biotechnology as well as on genomic medicine.

Archaea↗
PubMed2000

Determinants of the quantity of hepatitis C virus RNA.

To test the hypothesis that person-to-person variability in blood levels of hepatitis C virus (HCV) RNA can be explained, the quantity of HCV RNA was assessed in 969 persons who acquired HCV infection in the context of injection drug use. Serum HCV RNA levels ranged from 200,000 to >120 million equivalents/mL (the linear range of the assay). The median log10 HCV RNA level was 0.46 higher in 468 human immunodeficiency virus (HIV)-positive persons than in 501 HIV-negative persons (P<.001). In addition, among HIV-negative persons, lower HCV RNA levels were independently associated with younger age (P<.001), ongoing hepatitis B infection (P=.005), and the absence of needle sharing (P=.02). However, >90% of the person-to-person HCV RNA level variability was not explained by these sociodemographic, environmental, and virologic factors. Additional research is necessary to ascertain what determines the level of HCV RNA in blood.

Adult↗
PubMed2000

BCG vaccine effectiveness in preventing tuberculosis and its interaction with human immunodeficiency virus infection.

BACKGROUND: To explore Bacillus Calmette-Guérin vaccine (BCG) as a protective factor against tuberculosis (TB) and how human immunodeficiency virus (HIV) infection modifies the effect of BCG on TB. METHODS: Two matched case-control studies were conducted. One study compared TB cases and controls who were HIV positive. The second compared TB cases and controls who were HIV negative. The study population consisted of 88 TB cases and 88 controls among HIV-positive individuals and 314 TB cases and 310 controls among HIV-negative individuals. Cases were new TB diagnoses, confirmed by either bacteriology, pathology, radiology or clinical response to treatment; controls were selected from people without TB symptoms and who sought medical attention in the same institution where a case was enrolled. BCG was assessed by the presence of a typical scar. RESULTS: The level of protection against all clinical forms of TB was 22% among HIV positive individuals (odds ratio [OR] = 0.78, 95% CI : 0.48-1.26) and 26% among HIV negatives (OR = 0.74, 95% CI : 0.52-1.05). There was a significant difference (P = 0.002) in the level of protection against extrapulmonary TB (ETB) between HIV-negative (OR = 0.54, 95% CI : 0.32-0.93) and HIV-positive individuals (OR = 1.36, 95% CI : 0.72-2.57). CONCLUSION: BCG has a modest protective effect against all forms of TB independent of HIV status, and BCG confers protection against extrapulmonary TB among HIV-negative individuals. However, HIV infection seems to abrogate the protective effect of BCG against extrapulmonary TB. Our data support the public health importance of BCG vaccine in the prevention of extrapulmonary TB among immunocompetent individuals.

Adult↗
PubMed2000

A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor.

UNLABELLED: We previously found that the extent of an epidural motor block produced by 0.125% ropivacaine was clinically indistinguishable from 0.125% bupivacaine in laboring patients. By adding fentanyl to the 0. 125% ropivacaine and bupivacaine solutions in an attempt to reduce hourly local anesthetic requirements, we hypothesized that differences in motor block produced by the two drugs may become apparent. Fifty laboring women were randomized to receive either 0. 125% ropivacaine with fentanyl 2 microg/mL or an equivalent concentration of bupivacaine/fentanyl using patient-controlled epidural analgesia (PCEA) with settings of: 6-mL/hr basal rate, 5-mL bolus, 10-min lockout, 30-mL/h dose limit. Analgesia, local anesthetic use, motor block, patient satisfaction, and side effects were assessed until the time of delivery. No differences in verbal pain scores, local anesthetic use, patient satisfaction, or side effects between groups were observed; however, patients administered ropivacaine/fentanyl developed significantly less motor block than patients administered bupivacaine/fentanyl. Ropivacaine 0.125% with fentanyl 2 microg/mL produces similar labor analgesia with significantly less motor block than an equivalent concentration of bupivacaine/fentanyl. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the PCEA technique remains to be determined. IMPLICATIONS: By using a patient-controlled epidural analgesia technique, ropivacaine 0.125% with fentanyl 2 microg/mL produces similar analgesia with significantly less motor block than a similar concentration of bupivacaine with fentanyl during labor. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the patient-controlled epidural analgesia technique remains to be determined.

Adult↗
PubMed2000

Screening for hepatitis C virus in human immunodeficiency virus-infected individuals.

Immunosuppression from human immunodeficiency virus (HIV) may impair antibody formation, and false-negative hepatitis C virus antibody (anti-HCV) tests have been reported in individuals coinfected with HIV and HCV. It is unknown if the frequency of false-negative tests is sufficiently high to change screening recommendations in this setting. Thus, the prevalence of false-negative results for anti-HCV by third-generation tests was determined with samples from HIV-infected individuals. Sera from 559 HIV-infected and 944 HIV-negative prospectively followed injection drug users were tested for anti-HCV by a third-generation enzyme immunoassay and for HCV RNA by using a branched DNA assay and the HCV COBAS AMPLICOR system. Of 559 HIV-infected participants, 547 (97.8%) were anti-HCV positive. One of the remaining 12 anti-HCV-negative participants was HCV RNA positive, and she later developed detectable anti-HCV. Of the 944 HIV-negative participants, 825 (87.4%) were anti-HCV positive. One of the remaining 119 anti-HCV-negative participants was HCV RNA positive, and she also developed detectable anti-HCV at a later visit. These data indicate that HIV infection does not alter the approach to hepatitis C virus screening, which should be performed with third-generation assays for anti-HCV unless acute infection is suspected.

Adult↗
PubMed1999

Smart and biofunctional streptavidin.

The high affinity recognition of biotin and biotinylated molecules has made streptavidin one of the most important components in diagnostics and laboratory kits. While it is extremely useful as the native protein, there are many applications where its function can be improved re-engineering the subunits. We review here our efforts to construct streptavidin tetramers that have 'smart' recognition capabilities, and which display functional peptide sequences. These smart and biofunctional streptavidin derivatives can 'talk' to cells, and 'listen' to external signals which control capture and release of biotinylated molecules.

Affinity Labels↗
PubMed1999

Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

Bacterial Proteins↗
PubMed1999

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Archaea↗
PubMed1999

HIV-1 incidence among opiate users in northern Thailand.

The incidence of human immunodeficiency virus type 1 (HIV-1) infection among opiate users was determined in a retrospective cohort of 436 patients with multiple admissions to the only inpatient drug treatment program in northern Thailand between October 1993 and September 1995. During 323.4 person-years of follow-up, 60 patients presenting for detoxification acquired HIV-1 infection, for a crude incidence rate of 18.6 per 100 person-years (95% confidence interval 14.4-23.9). All seroconverters were male. HIV-1 incidence varied by the current route of drug administration: 31.3 per 100 person-years for injectors and 2.8 per 100 person-years for noninjectors (smoking and ingestion). Significant differences were found by ethnicity: HIV-1 incidence was 29.3 per 100 person-years for Thai lowlanders and 8.5 per 100 person-years for hill tribes. Multivariate relative risk estimates showed that injecting opiates (vs. use by other routes), being unmarried, being under age 40 years, being a Thai lowlander, having a primary and secondary education, and being employed in the business sector were each independently associated with human immunodeficiency virus seroconversion. This HIV-1 incidence rate is double that reported for Bangkok and suggests that prevention and control programs for drug users need to be expanded throughout Thailand. Improved availability of more-effective treatment regimens and increased access to sterile injection equipment are needed to confront the HIV-1 epidemic among opiate users in northern Thailand.

Adult↗
PubMed1999

A prospective, community-based evaluation of liver enzymes in individuals with hepatitis C after drug use.

Serum alanine transaminase (ALT) levels are used to select hepatitis C virus (HCV)-infected patients for treatment and liver biopsy. However, the natural history of these measurements is poorly understood. To examine the hypothesis that ALT levels vary over time in HCV-infected patients, serial serum ALT levels were prospectively measured in a cohort of 1,235 persons with a history of prior illicit drug use. Over 25 months of follow-up, there was a median of four evaluations per patient. ALT values were higher in 1,164 (94%) HCV-infected individuals than in 71 (6%) HCV-uninfected individuals. The remainder of the analysis focused on these HCV-infected individuals, 647 (62%) of whom had normal ALT values at their initial visit. However, 323 (49%) of these had at least one elevated ALT over the next 25 months. Of the 395 patients whose ALT was initially abnormal, 332 (84%) had at least one normal value over the next 25 months. Overall, among individuals with four or more visits, ALT values were persistently normal in 42%, persistently elevated in 15%, and intermittently elevated in 43%. Because serum ALT levels have high visit-to-visit variability, single assessments should not be used to manage HCV-infected individuals. Further investigation is needed to ascertain the correlation of serial ALT trends with important disease outcomes.

Adult↗
PubMed1999

Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection.

The purpose of this investigation was to prospectively characterize acute hepatitis C virus (HCV) infections and to evaluate the hypothesis that the outcome is affected by identifiable clinical or viral factors. One hundred forty-two people with a history of illicit drug use who were HCV antibody-negative in 1988 were followed semiannually through 1996. HCV seroconversion (second generation enzyme immunoassay and recombinant immunoblot assay) was recognized in 43 (30%) of the participants, who were followed up for a median of 72 months. HCV RNA was detected and quantified by polymerase chain reaction in a median of 10 specimens per participant and showed two distinct patterns of viremia: viral clearance was noted in 6 (14%) of the participants, and viral persistence was observed in 37 (86%) of the participants. Subjects with viral clearance were more likely to be white (P =.004), have jaundice (P =.03), and have lower peak viral titer (P =.003). However, the outcome for a given person could not be predicted by clinical features, RNA level, or HCV subtype (as ascertained by analysis of core-E1 complementary DNA sequence). No acute infections were recognized by health care providers. At the time of seroconversion, HCV RNA was detectable in 81% of participants, and recombinant immunoblot assay (RIBA) was positive in 85% of participants. We conclude that approximately 85% of people with acute hepatitis C develop persistent viremia. However, acute infections are uncommonly recognized clinically, underscoring the importance of screening individuals at risk. Long-term follow-up, but no single laboratory test, is necessary to ascertain the outcome and in some cases make the diagnosis of acute HCV infection.

Adult↗
PubMed1999

Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand. Chiang Mai HEPS Working Group.

Characterization of persons highly exposed to human immunodeficiency virus (HIV)-1 who remain uninfected may help define protective immunity. Seventeen HIV-1-seronegative Thai female sex workers (CSWs) with epidemiologic evidence of exposure to HIV-1 were studied for humoral immune responses and phenotypic and genotypic analyses of HLA class I and CCR5 allelic profiles. Infected CSWs and low-risk HIV-1-seronegative Thai women were controls. Highly exposed, persistently seronegative (HEPS) CSWs did not differ from HIV-infected CSWs in HIV risks, condom use, or sexually transmitted diseases. Significant differences were seen in humoral immune responses: gp160-specific IgA responses were detected in cervicovaginal lavage fluids in 6 of 13 HEPS CSWs but 0 of 21 seronegative subjects. All women had wild-type CCR5. HEPS CSWs were more likely to have the HLA-B18 phenotype and genotype than were matched controls (corrected P=.018). Epidemiologic exposure to HIV-1 without apparent infection, an unusual distribution of HLA class I alleles, and HIV-1 gp160-specific IgA responses suggest a biologic basis for this phenomenon.

Adolescent↗
PubMed1999

Class II HLA alleles and hepatitis B virus persistence in African Americans.

Persistence of hepatitis B virus (HBV) infection is likely due to the interplay of the virus and host immune response. Given its critical role in antigen presentation, allelic differences in the HLA complex may affect HBV persistence. In a prospectively followed African American cohort, molecular class I and class II HLA typing was done on 31 subjects with persistent HBV infection and 60 controls who cleared the infection. HBV persistence was significantly associated with two class II alleles, DQA1 *0501 (odds ratio [OR], 2.6; P=.05) and DQB1 *0301 (OR, 3.9; P=.01), the two-locus haplotype consisting of these same two alleles (OR, 3; P=. 005) and the three-locus haplotype, DQA1 *0501, DQB1 *0301, and DRB1 *1102 (OR, 10.7; P=.01). In addition, HBV persistence was associated with class II allelic homozygosity. Several class I associations with persistence were also noted but were not statistically significant after correction for multiple comparisons. These results underscore the importance of the class II-mediated immune response in recovery from HBV infection.

Adult↗
PubMed1999

High rates of transmission of subtype E human immunodeficiency virus type 1 among heterosexual couples in Northern Thailand: role of sexually transmitted diseases and immune compromise.

The heterosexual transmission of subtype E human immunodeficiency virus type 1 (HIV-1) infection was evaluated in 467 couples in Thailand in whom the man was HIV-1 positive and the woman had no risk factors for HIV other than sex with her infected partner. At baseline, 216 (46.3%) of the 467 women were positive for HIV-1; prevalence of HIV among women was 52.2% when their male partners had CD4+ lymphocyte counts of <200 cells/microL, 45.9% in women whose partners had counts of 200-499 micro/L, and 39.2% in women whose partners had counts of >/=500/microL. Women were twice as likely to be HIV positive if their partners had a history of a sexually transmitted disease (STD); however, their HIV prevalence was 29% among couples who had no STD history. It appears that female partners of men infected with subtype E HIV-1 are at high risk of infection even when the man's CD4+ cell count is relatively high. A high rate of STDs may contribute significantly to this risk [corrected].

Blood Donors↗
PubMed1999

Intrathecal neostigmine and sufentanil for early labor analgesia.

BACKGROUND: Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal neostigmine in combination with intrathecal sufentanil to investigate the usefulness of neostigmine for reducing side effects and prolonging the duration of sufentanil. METHODS: One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus neostigmine, 10 microg. RESULTS: Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus neostigmine, 10 microg) were similar between groups. CONCLUSIONS: The 10-microg intrathecal neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.

Adult↗
PubMed1998

HIV type 1 subtypes in Malaysia, determined with serologic assays: 1992-1996.

We investigated the molecular epidemiology of HIV-1 subtypes in Malaysia among injecting drug users (IDUs) and sexual transmission risk groups, using serologic and genetic techniques. Frozen sera collected at a general hospital, a blood bank, several drug treatment centers, and an STD clinic in Kuala Lumpur, between 1992 and 1996, were investigated retrospectively. V3 peptide serotyping and monomeric gp120 capture serotyping were used to study 89 known HIV-1-infected subjects. The methods differentiate subtypes B, E, and C. V3 peptide and gp120 capture results were comparable. No subtype C-specific reactive sera were found; one specimen was dually reactive for subtypes C and B, using the V3 peptide ELISA; and four were durally reactive for subtypes E and C using this assay. Genotypic analysis of HIV-1 gag RNA in serum was done on a subset of subjects and confirmed serologic findings. HIV-1 subtypes differed significantly by risk category: of 53 IDUs, 29 (55%) were infected with subtype B and 19 (36%) were infected with subtype E, 3 (6%) were dually reactive, and 2 (4%) were not typable. Of 36 persons with heterosexual risks, 29 (81%) were infected with subtype E, 5 (14%) were infected with subtype B, and 2 (5%) were not typable. Persons with IDU risks were significantly more likely to be infected with subtype B than were those with sexual risks (OR 5.89; 95% CI, 1.94-18.54; p < 0.001). Subtypes B and E of HIV-1 appear to predominate in Malaysia; subtype B was more prevalent among IDUs; subtype E was more prevalent among all other groups. These results may have important HIV-1 vaccine implications.

Amino Acid Sequence↗