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J S Sullivan

Publications and source records attributed to J S Sullivan.

At least 19 recordsLinked to original sources
PubMed1996

Comparative assessment of pediatric intensive care in Moscow, the Russian Federation: a prospective, multicenter study.

OBJECTIVE: Comparative assessment of pediatric intensive care. DESIGN: Prospective multicenter study. SETTING: Four pediatric intensive care units in Moscow, the Russian Federation. PATIENTS: Consecutive unselected admissions (n = 583), < or = 14 yrs of age, in a 6-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Effectiveness was defined as the ratio of observed to predicted mortality, based on prediction by Pediatric Risk of Mortality (PRISM) severity of illness scoring. Efficiency (on the day of admission only) depended on either a mortality risk of > 1% or the administration of intensive care unit-dependent therapies. In all four hospitals, observed mortality rates were higher than expected, with a range of standardized mortality ratios between 1.10 and 1.83 (mean 1.32). The excess mortality was found in the low- and medium-risk strata (risk of mortality of < 1% to 15%). Admission efficiency ratings did not fluctuate greatly between institutions (mean 60.4%, range 55.7 to 65.9). CONCLUSIONS: We provided a quantitative description and assessment of pediatric intensive care in Moscow. Moderate efficiency may reflect a low threshold for ICU admission due to poor nurse/patient ratios on the wards. Effectiveness in the low- and medium-risk strata is below standard, as compared with a Western reference population. Excess mortality was concentrated in the low- and medium-risk strata, and can only partially be explained by the inclusion of co-morbidity. Future analysis should focus on specific treatment protocols, protocol adherence, and the determination of infectious and therapeutic complications.

Child↗
PubMed1996

Twin studies demonstrate a host cell genetic effect on productive human immunodeficiency virus infection of human monocytes and macrophages in vitro.

Biological and genetic variability is a prominent feature of human immunodeficiency virus (HIV) strains, especially in tropism, syncytium formation, and replicative capacity. To determine whether there were variable host cell effects on HIV replication in monocytes, three different strains of low-passage-number monocytotropic blood isolates of HIV and the laboratory-adapted strain Ba-L were inoculated into panels of adherent monocytes drawn from 44 different donors, and peak extracellular HIV p24 antigen titers were compared. The clinical HIV strains showed patterns of either moderate or low-level replication in most donor monocytes (20 to 4,000 pg/ml). However, within this range there was marked variation in peak titers in most donors. HIV type 1 Ba-L replicated in all donor monocytes to much higher levels with less variability (30 to 40 ng/ml). Furthermore, replication of 21 clinical blood-derived strains of HIV in blood monocytes and monocyte-derived macrophages (MDM) from pairs of identical twins and age-matched unrelated donors (URD) of the same sex were compared. In all of the seven pairs of identical twins, the kinetics of replication (measured by extracellular HIV p24 antigen) of panels of four clinical HIV type 1 isolates in monocytes were similar within pairs. However, marked and significant differences in kinetics of HIV production occurred within 10 of the 12 unrelated donor pairs (P = 0.0007). The remaining two URD pairs showed similar kinetic patterns, but only one pair had the same HLA-DR genotype. Similar results were observed with monocytes/MDMs obtained from a second bleed of the same donor. Hence, discordant patterns of HIV replication kinetics between URD monocyte pairs contrasted with concordant patterns in identical twin monocytes. These data strongly suggest a host cell genetic effect on productive viral replication in monocytes and MDMs. So far, no consistent genetic linkage of HIV replication pattern with HLA-DR genotype has been observed.

Adult↗
PubMed1996

The Santa Lucia strain of Plasmodium falciparum as a model for vaccine studies. I. Development in Aotus lemurinus griseimembra monkeys.

The Santa Lucia strain of Plasmodium falciparum and the Aotus lemurinus griseimembra monkey are proposed as models for the testing of sporozoite vaccines and transmission-blocking vaccines. Approximately 85% of splenectomized monkeys were infected when fed upon by 10 or more heavily infected Anopheles freeborni mosquitoes. Sporozoite-induced infections in monkeys with or without previous infection with P. vivax readily infected mosquitoes, thus making them candidates for testing transmission-blocking vaccines.

Animals↗
PubMed1996

The Santa Lucia strain of Plasmodium falciparum as a model for vaccine studies. II. Development of Aotus vociferans as a model for testing transmission-blocking vaccines.

The Santa Lucia strain of Plasmodium falciparum and the Aotus vociferans monkey were studied as models for the testing of transmission-blocking vaccines. Virulence developed early in the passage history. Despite the use of only small quantities of chlorguanide and/or quinine to control infection coupled with the use of small inocula and delays in splenectomy, mosquito infection was markedly reduced from that seen during primary passage to this species of Aotus. It appears that the model may be most useful during its initial passage from the primary species, Aotus lemurinus griseimembra.

Animals↗
PubMed1996

Plasmodium vivax infections in chimpanzees for sporozoite challenge studies in monkeys.

The development and testing of vaccines directed against Plasmodium vivax has relied on Saimiri and Aotus monkeys as the animal test system and on chimpanzees to provide infective gametocytes to produce sporozoites for monkey challenge studies and vaccine development. One sporozoite-induced and 29 blood-induced infections with the Salvador I strain of P. vivax were studied in splenectomized chimpanzees. Eighteen primary infections with P. vivax resulted in maximum parasite counts ranging from 1,519 to 81,810/ microliters (median 29,100/microliters). Twelve infections induced in animals previously infected with the homologous or heterologous strains of P. vivax had maximum parasite counts ranging from 155 to 14,136/microliters (median 1,736/microliters). A total of 202 of 237 lots containing a total of 293,175 Anopheles freeborni, An. stephensi, An. gambiae, An. dirus, An. quadrimaculatus, and An. maculatus mosquitoes were infected by membrane feeding on gametocytes from chimpanzees. Despite lower levels of parasitemia during secondary (reinfection) parasitemia, 66 of 70 lots of mosquitoes (94.3%) were infected. Based on the mean number of oocysts per positive mosquito gut, An. freeborni was more heavily infected than An. stephensi; An. stephensi was more heavily infected than An. gambiae; there was no significant difference between An. stephensi and An. dirus. Sporozoites from An. stephensi, An. gambiae, An. dirus, and An. freeborni infected with the Salvador I strain of P. vivax produced in chimpanzees were used to infect 193 Saimiri and six Aotus monkeys as well as one chimpanzee.

Animals↗
PubMed1996

Observations on the biological nature of Plasmodium vivax sporozoites.

The relapsing malaria parasites are characterized by the production of sporozoites with varying potential for exoerythrocytic development. Some sporozoites develop soon after introduction to produce mature schizonts and merozoites that initiate the erythrocytic stage infection. Relapsing hypnozoite forms are characteristic of some strains of Plasmodium vivax and are more apt to develop late than early with many time intervals in between. Studies in Saimiri monkeys suggest another type of sporozoite-induced infection. With the Salvador I strain of P. vivax, early developing exoerythrocytic schizonts apparently release parasites with different levels of virulence for these monkeys, ranging from those producing high-level parasitemia to a more abundant avirulent form. The induction of low-density avirulent infections requires the development of more sensitive detection methods for the evaluation of sporozoite vaccines.

Animals↗
PubMed1996

Sporozoite transmission of three strains of Plasmodium knowlesi to Aotus and Saimiri monkeys.

Attempts were made to infect Aotus and Saimiri monkeys with sporozoites of 3 strains of Plasmodium knowlesi to determine the potential of these animals in a monkey/malaria model. Splenectomized Saimiri and Aotus monkeys were infected with the H strain of P. knowlesi via sporozoites from Anopheles dirus mosquitoes. Prepatent periods ranged from 5 to 16 days. Saimiri monkeys infected with the Philippine strain had prepatent periods ranging from 6 to 8 days. Saimiri monkeys infected with the Hackeri strain had prepatent periods ranging from 6 to 11 days. Exoerythrocytic (EE) stages of the Philippine strain were readily demonstrated; EE stages of the H strain were less abundant. Results indicate that the Philippine strain of P. knowlesi in Saimiri monkeys has a course of parasitemia and EE stages similar to those previously seen in macaques and could serve as a reproducible model for biologic and immunologic studies.

Animals↗
PubMed1996

The Nigerian I/CDC strain of Plasmodium ovale in chimpanzees.

The chimpanzee is the only animal host currently available that can support the development of the human malaria parasite Plasmodium ovale. Thirty-one infections with the Nigerian I/CDC strain were induced in splenectomized chimpanzees. Maximum parasite counts ranged from 1,240 to 127,224/microliters. Infections were transient and unpredictable. Anopheles stephensi, Anopheles gambiae, Anopheles freeborni, and Anopheles dirus mosquitoes were infected by feeding through parafilm membranes on heparinized blood containing gametocytes; each species supported development to sporozoites in the salivary glands. Mean oocyst counts per infected mosquito ranged from 1 to 85.1; 21.7% of infected lots of mosquitoes averaged > 20 oocysts per positive mosquito gut. One infection was induced via the bites of infected An. gambiae. The prepatent period was 16 days.

Animals↗
PubMed1995

Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.

Adult↗
PubMed1995

HIV and AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Use of the rhesus monkey as an experimental model to test the degree of efficacy of an anti-sporozoite peptide malaria vaccine candidate combined with copolymer-based adjuvants.

Humoral response against sporozoites is not effective in protecting individuals from getting malaria. Reduction in the infectivity of sporozoites has not been quantified for most anti-sporozoite vaccines tested. Quantification requires animal models providing predictable prepatent periods, e.g., time elapsed between sporozoite inoculation and detection of parasitemia, to be used as an indicator of activity against sporozoites. A delay in prepatent period from vaccinated animals would therefore reflect a protective effect in reducing the number of parasites. We report the vaccination of rhesus monkeys with a synthetic peptide reproducing part of the repeated region of the circumsporozoite protein of Plasmodium cynomolgi. This peptide was conjugated to the carrier protein diphtheria toxoid and injected with four adjuvant formulations that differed only by the type of emulsion or immunomodulator. Because all five control animals had a synchronous prepatent period after challenge with live sporozoites, it was possible to quantify the protective efficacy for each vaccine formulation, even though all monkeys developed parasitemia. Sporozoite elimination correlated with the immunomodulator and the type of emulsion. Such elimination was related neither to antibody titer against the immunizing peptide or the whole sporozoite, nor to antibody isotype induced by the vaccine formulation.

Adjuvants, Immunologic↗
PubMed1994

Plasmodium ovale: observations on the parasite development in Saimiri monkey hepatocytes in vivo and in vitro in contrast with its inability to induce parasitemia.

Exoerythrocytic stage parasites of the human malaria parasite Plasmodium ovale were cultured in vitro by inoculating primary cultures of hepatocytes from Saimiri sciureus boliviensis monkeys with sporozoites. Morphology and size of the liver stages were similar to previous in vivo descriptions in humans and chimpanzees. Saimiri monkeys did not develop parasitemia after repeated inoculations with P. ovale sporozoites. However, liver-stage parasites were observed in liver biopsies performed 7 days after sporozoite inoculation. Together with observations on other parasite development, these results demonstrate that host specificity for many malaria parasites occurs at the blood-stage level. Lack of host specificity of primary malaria parasite species for the liver forms the basis for the close relationship existing between human and nonhuman primate malaria species.

Animals↗
PubMed1994

Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis.

We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor necrosis factor (TNF) are elevated in critically ill infants with sepsis and necrotizing enterocolitis (NEC) and that the magnitude of their elevation is correlated with mortality rate. We measured plasma levels of interleukin-6 and TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative culture results. Twenty comparably ill infants with negative results on culture of systemic specimens served as study control subjects. Interleukin-6 levels were five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of disease than in infants with bacterial sepsis alone, in infants with NEC but negative culture results, and in control infants (p < 0.01). These differences persisted throughout the 48-hour study period. Interleukin-6 levels were also significantly higher in nonsurvivors than in survivors (p < 0.001). In contrast, plasma TNF values were not consistently increased in any of the groups. We conclude that plasma interleukin-6 is a more reliable indicator of bacterial sepsis and NEC than plasma TNF and may identify infants who might benefit from immunotherapeutic strategies.

Analysis of Variance↗
PubMed1994

Selection of different strains of Plasmodium falciparum for testing blood-stage vaccines in Aotus nancymai monkeys.

Three strains of Plasmodium falciparum, Vietnam Oak Knoll (FVO), Uganda Palo Alto (Hawaii) (FUP-H) and Uganda Palo Alto (Cayenne) (FUP-C), were examined in 154 Aotus nancymai monkeys as suitable models for testing blood-stage vaccines. The Vietnam Oak Knoll strain had the greatest number of animals with maximum parasite counts > 200,000/microliters. Uniformity of the parasitemia curve increased from passage 4 to passage 6 with an accompanying decrease in the number of days required to reach maximum parasitemia or required treatment. The Uganda Palo Alto (Hawaii) strain was highly infectious, but many animals had extended prepatent periods and extended days to maximum parasitemia. The FUP-H strain would require a greater number of animals per test group to detect partial protection because of the greater number of low-density maximum parasite counts in control animals. The Uganda Palo Alto (Cayenne) strain was poorly adapted to intact A. nancymai. However, five of six splenectomized monkeys inoculated during passage 6 with 10(5) parasites had maximum parasite counts > 200,000/microliters. For the testing of vaccines against primary parasitemia in the A. nancymai model system, the FVO at passage 4 level would appear preferable to passage 6 parasites following a challenge with 10(5) parasites. A similar pattern could be obtained using FUP-H if the challenge was 10(6) parasites. To measure immune memory against recrudescence or rechallenge infection, FUP-C at an early passage in splenectomized A. nancymai would appear to be the appropriate model.

Animals↗
PubMed1994

Protective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of Plasmodium fragile.

Saimiri sciureus boliviensis monkeys were immunized with the Plasmodium fragile form of the merozoite apical membrane antigen-1 produced using the baculovirus expression system and combined with Montanide ISA 720 adjuvant. Following three immunizations, monkeys were challenged with 10,000 P. fragile trophozoite parasites. Antibody titers determined by fluorescence microscopy indicated an enhanced response following the second immunization. Four of five control animals had parasite counts > 5% 18-26 days following challenge. Four of five immunized monkeys had reduced levels of maximum parasitemia or delays in accumulated parasite counts, suggestive of protection. Rechallenge of the animals with P. falciparum resulted in three of four adjuvant control animals developing patent parasitemia whereas none of five immunized animals were infected, suggesting some level of heterologous protection.

Adjuvants, Immunologic↗