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Biomedical subjects

D R Clark

Publications and source records attributed to D R Clark.

At least 19 recordsLinked to original sources

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts.

Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P <.001) and reduced thymic output in infants of HIV-positive mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P <.001). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function.

Anti-HIV Agents↗

Grignard reactions of 4-substituted-2-keto-1,3-dioxanes: highly diastereoselective additions controlled by a remote alkyl group.

[see reaction]. The reactions of Grignard reagents with a representative series of simple cis-2-keto-4-substituted-1,3-dioxanes have been investigated. The stereochemical outcome of these highly diastereoselective additions (dr > 90:10) is consonant with Cram's chelate model on the assumption that RMgX coordinates preferentially with the ring oxygen remote from the C(4) substituent.

Journal Article↗

DDT and the decline of free-tailed bats (Tadarida brasiliensis) at Carlsbad Cavern, New Mexico.

DDT is believed to have caused the population of Brazilian free-tailed bats (Tadarida brasiliensis mexicana) at Carlsbad Cavern to decline severely after 1936. Nevertheless, previous data supporting this hypothesis are limited to a single study from 1974, which indicated that 20% of young free-tails from the cavern may have died of DDE poisoning during their first southward migration. In this study I compared organochlorine residues among samples of free-tails collected in Carlsbad Cavern in 1930, 1956, 1965, 1973, and 1988. Samples of skin cut from dry museum specimens were chemically analyzed, except for the 1973 data, which were derived from analyses of whole bats minus gastrointestinal tracts. Accumulated residue levels of DDT compounds in bats from 1965 and 1956 exceeded those in 1973 bats by approximately 4.8 times and approximately 2.7 times, respectively. This suggests that lethal effects of DDT compounds were substantially greater in the 1950s and 1960s than in the 1970s. Residues in 1988 bats resembled those for 1973 bats. It is concluded that DDT played a major role in this severe population decline. These results can be applied by management personnel in evaluating the present and future status of this population regarding persisting organochlorine insecticides as well as other agricultural chemicals now in use. The case of the Carlsbad colony is discussed relative to the general issue of other bat population declines.

Animals↗

Dicofol residues in eggs and carcasses of captive American kestrels.

American kestrels (Falco sparverius) were fed diets containing 0 (control), 1, 3, 10, and 30 microgram/g (wet wt) of Kelthane. Residues of dicofol and its metabolites were then analyzed in the eggs and carcasses of females. Significant differences occurred among treatments for residues of both p,p'-dicofol and p,p'-dechlorodicofol (DCD) in both eggs and carcasses and for p,p'-dicholorbenzophenone (DCBP) in eggs. Residue concentrations increased with increasing treatment exposure. Residues of p,p'-dicofol, p,p'-DCD, and p,p'-DCBP in eggs were significantly correlated with eggshell quality parameters. Significant correlations also occurred among contaminants in eggs and for individual contaminants between eggs and carcasses. The lowest-observed-dietary-effect concentration for eggshell thinning was 3 microgram/g, whereas 1 microgram/g may be considered to be near a no-observable-adverse-effect concentration. Concentrations of dicofol in potential prey items and eggs of wild birds generally have been lower than dietary-effect concentrations or concentrations in tissues or eggs associated with eggshell thinning and reduced reproductive success.

Animals↗

T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy.

Impairment of T-cell renewal has been proposed as contributing to CD4(+) T-cell depletion in persons infected with human immunodeficiency virus-1. We analyzed the T-cell development capacity of progenitors using fetal thymus organ culture. Those who progressed to AIDS had a dramatic loss in T-cell development capacity shortly after seroconversion. In contrast, long-term nonprogressors retained progenitor capacity 8 years after seroconversion. Approximately 70% of patients experienced an improvement in T-cell development capacity after receiving 6 months of potent antiretroviral therapy. Improvement in T-cell development in fetal thymus organ culture correlated with an increase in the number of naive CD4(+) T cells in peripheral blood. Numbers of progenitors in blood and bone marrow after seroconversion or during therapy did not correlate with the change observed in T-cell development capacity. These data provide evidence that HIV-1 infection can interfere with T-cell renewal at the level of the progenitor cell. Interference with T-cell renewal may contribute to CD4(+) T-cell depletion.

Acquired Immunodeficiency Syndrome↗

The relationship between the dissolved inorganic carbon concentration and growth rate in marine phytoplankton.

A range of marine phytoplankton was grown in closed systems in order to investigate the kinetics of dissolved inorganic carbon (DIC) use and the influence of the nitrogen source under conditions of constant pH. The kinetics of DIC use could be described by a rectangular hyperbolic curve, yielding estimations of KG(DIC) (the half saturation constant for carbon-specific growth, i.e. C mu) and mu max (the theoretical maximum C mu). All species attained a KG(DIC) within the range of 30-750 microM DIC. For most species, NH4+ use enabled growth with a lower KG(DIC) and/or, for two species, an increase in mu max. At DIC concentrations of > 1.6 mM, C mu was > 90% saturated for all species relative to the rate at the natural seawater DIC concentration of 2.0 mM. The results suggest that neither the rate nor the extent of primary productivity will be significantly limited by the DIC in the quasi-steady-state conditions associated with oligotrophic oceans. The method needs to be applied in the conditions associated with dynamic coastal (eutrophic) systems for clarification of a potential DIC rate limitation where cells may grow to higher densities and under variable pH and nitrogen supply.

Carbon↗

Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons.

An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability of CD34+ progenitor cells to generate lymphocytes was examined by use of thymic organ cultures. The mean number of lymphocytes generated per CD34+ cell on day 0 was 0.72 and on day 4 was 0.09 (P<.003). The number of CD4+ cells generated per CD34+ cell was significantly reduced after G-CSF treatment. Thus, G-CSF increased the number of mature progenitor cells but did not increase T cell progenitors.

Animals↗

Peripheral blood from human immunodeficiency virus type 1-infected patients displays diminished T cell generation capacity.

An organ culture chimera system was used to assess the effect of human immunodeficiency virus type 1 (HIV-1) infection on the T cell-generation capacity of precursors derived from human peripheral blood. Peripheral blood mononuclear cells from HIV-1-infected patients and uninfected controls were placed on fetal thymus lobes of NOD/LtSz-scid/scid mice. Blood from the HIV-1-infected patients consistently produced fewer CD4 and CD8 cells compared with blood from controls (P < .01). Addition of zidovudine to the cultures did not alter this profile. Limit dilution experiments suggested that there were fewer functional precursors in the infected patients. These results were not dependent on the patient's level of peripheral CD4 cells; even samples from patients with normal CD4 cell counts were unable to generate T cells in organ cultures. The results are consistent with a loss in the capacity of HIV-1-infected patients to produce functional T cell progenitors in their peripheral blood.

Animals↗

Noninvasive positive pressure ventilation.

Noninvasive positive pressure ventilation (NPPV) has been used in treatment of a variety of clinical conditions, including acute respiratory failure (ARF) due to status asthmaticus. We present the case of a patient admitted with acute exacerbation of asthma who had ARF and required mechanical ventilation. After extubation, he had respiratory distress and was successfully treated with NPPV. NPPV was continued for approximately 24 hours, with clinical improvement and avoidance of reintubation. Despite the benefits of NPPV (ie, improved patient comfort, reduced need for sedation, and avoidance of complications associated with mechanical ventilation), it has not been widely used. Understanding the clinical indications for and limitations of NPPV allows successful use of this noninvasive method of mechanical ventilation.

Adult↗

Restriction endonucleases in clinical isolates of Shigella spp.

Thirteen restriction endonuclease-containing strains were isolated from a collection of 186 clinical isolates of Shigella spp. Among these, eight and five isolates carried isoschizomers of EcoRII and NciI, respectively. The former restriction-modification (R-M) system was homologous to that of EcoRII and was located on plasmids with sizes of 46.6 or 55.6 kb. Isolates producing NciI isoschizomers contained a 5.7-kb non-transferable plasmid. Together with antimicrobial susceptibility tests and plasmid profile studies, it is concluded that these two R-M systems are not widely spread but confined to strains with similar antibiotic resistance and plasmid profile.

Anti-Bacterial Agents↗

A new scale for in-home test-weighing for mothers of preterm and high risk infants.

The purposes of this research were to describe the accuracy of test-weighing with the BabyWeigh, a new infant scale suitable for use in the home, and to determine whether mothers and investigators could estimate intake accurately during breastfeeding sessions, using clinical cues that are recommended for this purpose. Within five days of projected NICU discharge, 30 preterm and/or high risk infants and their mothers were studied during a single breastfeeding session. A member of the research team performed test-weights with the Smart Model 20 infant scale, and mothers performed test-weights with the BabyWeigh scale. The mothers and investigators each estimated volume of intake for the breastfeeding session using clinical cues. Mothers and investigators were blind to each others' test-weights and clinical estimates. Results revealed that the BabyWeigh scale provided an accurate estimate of intake during breastfeeding across a large range of infant weights and intake volumes. In contrast, investigator and maternal estimates of intake were not sufficiently accurate.

Adult↗

Uptake of environmental contaminants by small mammals in pickleweed habitats at San Francisco Bay, California.

Small mammals were live-trapped in pickleweed (Salicornia virginica) habitats near San Francisco Bay, California in order to measure the uptake of several contaminants and to evaluate the potential effects of these contaminants on the endangered salt marsh harvest mouse (Reithrodontomys raviventris). Tissues of house mice (Mus musculus), deer mice (Peromyscus maniculatus), and California voles (Microtus californicus) from nine sites were analyzed for chemical contaminants including mercury, selenium, cadmium, lead, and polychlorinated biphenyls (PCBs). Concentrations of contaminants differed significantly among sites and species. Mean concentrations at sites where uptake was greatest were less than maximum means for the same or similar species recorded elsewhere. Harvest mice (Reithrodontomys spp.) were captured only at sites where concentrations of mercury or PCBs were below specific levels in house mice. Additional studies aimed at the protection of the salt marsh harvest mouse are suggested. These include contaminant feeding studies in the laboratory as well as field monitoring of surrogate species and community structure in salt marsh harvest mouse habitats.

Animals↗

BsiY I, a novel thermophilic restriction endonuclease that recognizes 5' CCNNNNNNNGG 3' and the discovery of a wrongly sequenced site in pACYC177.

A new type II restriction endonuclease designated BsiY I has been purified from a thermophilic soil Bacillus stearothermophilus strain. This enzyme recognizes and cleaves the highly degenerate sequence 5' CCNNNNN!NNGG 3'. During the identification of the recognition sequence of BsiY I, we discovered that there should be five G nucleotides instead of four at position 1227-1230 of the plasmid pACYC177.

Base Sequence↗

Intrageneric relationships of members of the genus Fusobacterium as determined by reverse transcriptase sequencing of small-subunit rRNA.

The phylogenetic interrelationships of 14 members of the genus Fusobacterium were investigated by performing a comparative analysis of the 16S rRNA sequences of these organisms. The sequence data revealed considerable intrageneric heterogeneity. The four species Fusobacterium nucleatum (including F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, "F. nucleatum subsp. fusiforme," and "F. nucleatum subsp. animalis"), Fusobacterium alocis, Fusobacterium periodonticum, and Fusobacterium simiae, which colonize oral cavities, exhibited high levels of sequence homology with each other and formed a distinct group within the genus. Fusobacterium mortiferum, Fusobacterium varium, and Fusobacterium ulcerans also formed a phylogenetically coherent group, as did the two species Fusobacterium gonidiaformans and Fusobacterium necrophorum. Fusobacterium russii and Fusobacterium necrogenes displayed no specific relationship with any of the other fusobacteria. The sequence data are discussed in the context of previous physiological and chemical findings.

Base Sequence↗