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Biomedical subjects

C L Morris

Publications and source records attributed to C L Morris.

At least 37 records · Page 2Linked to original sources
PubMed1996

Acute graft-versus-host disease in children: abdominal CT findings.

PURPOSE: To review the computed tomographic (CT) appearance of acute gastrointestinal graft-versus-host disease (GVHD) in children. MATERIALS AND METHODS: Sixteen abdominal CT scans obtained in 12 children with acute gastrointestinal GVHD who underwent allogeneic bone marrow transplantation (BMT) were compared with 16 CT scans obtained in autologous bone marrow recipients not at risk for GVHD (control group). Autopsy findings in six patients with GVHD were compared with CT findings. RESULTS: All CT scans in patients with GVHD showed an abnormally enhanced, thin mucosal layer of bowel wall involving fluid-filled, dilated, poorly opacified bowel loops from the duodenum to the rectum. This corresponded histologically to mucosal destruction and replacement by a thin layer of highly vascular granulation tissue. Bowel wall thickening was often absent. Infiltration of mesenteric fat was seen in 91% of patients The control group showed no similar abnormalities. CONCLUSION: Acute gastrointestinal GVHD characteristically appears on CT scans as multiple, diffuse, fluid-filled bowel loops with a thin, enhancing layer of bowel wall mucosa. Bowel wall thickening often is absent.

Acute Disease↗
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

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

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

Further studies on the sporozoite transmission of the Salvador I strain of Plasmodium vivax.

Different species of Saimiri and Aotus monkeys were inoculated with sporozoites of the Salvador I strain of Plasmodium vivax. Of 58 Saimiri inoculated, 45 developed parasitemia (4 following bites and 41 following intravenous inoculation). Prepatent periods ranged from 10 to 63 days. Twelve of 19 monkeys inoculated with sporozoites that had been stored frozen developed patent parasitemia after 16-53 days. Of 41 Aotus monkeys inoculated, only 10 (2 via bites and 8 via intravenous inoculation) developed parasitemia. One of 7 Aotus inoculated with sporozoites that had been frozen developed parasitemia with a prepatent period of 26 days. Mosquitoes were infected by feeding on gametocytes from Aotus and Saimiri monkeys, chimpanzees, and a human. Sporozoites from Anopheles stephensi, Anopheles freeborni, Anopheles dirus, and Anopheles gambiae induced infection.

Animals↗
PubMed1993

Deoxygenation-induced changes in sickle cell-sickle cell adhesion.

The tendency for sickle cells to adhere to each other is increased in oxygenated sickle blood in parallel with cell density. The increased adherence of these cells occurred despite their reduced deformability and diminished ability to form rouleaux. Using a method developed in our laboratory, we measured the yield stress: a sensitive index of cell-cell adhesion of deoxygenated suspensions of sickle cells. Deoxygenation of whole sickle blood to 30 to 50 mm Hg caused a significant increase in yield stress of all sickle blood samples. Deoxygenation caused a significant increase in yield stress of both dense and light sickle cells. Deoxygenation-induced increases in yield stress occurred at higher oxygen tensions for dense (> 55 mm Hg) than for light sickle cells (< 45 mm Hg). The increase in yield stress on deoxygenation was correlated with hemoglobin polymerization as assessed morphologically by sickling or by changes in relative viscosity. Thus, deoxygenation-induced cell sticking must involve small areas of strong membrane adhesion because the changes in yield stress occurred despite a reduction in rouleaux formation and surface area of membrane contact. Sickle trait red blood cells also exhibited increased yield stress on deoxygenation but only under hypertonic conditions where sickling occurred. Thus, deoxygenation-induced cell adhesion did not require prior membrane damage because it occurred in sickle trait cells. No change in yield stress was seen when deoxygenated sickle cells were suspended in buffer, but the addition of physiologic amounts of fibrinogen to buffer restored the deoxygenation-induced increase in cell adhesion. We speculate that the increase in sticking among sickle cells on deoxygenation results from spicule formation and may involve interaction of fibrinogen and possibly other plasma proteins with the cell membrane.

Anemia, Sickle Cell↗
PubMed1993

Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population.

STUDY OBJECTIVE: To determine the extent of drug removal by emesis at different times after the ingestion of a toxic substance. DESIGN: Multicenter retrospective chart review. METHODS: Using the American Association of Poison Control Centers' aggregate data base, children who had ingested acetaminophen and who were referred to a health care facility by one of 11 poison centers during a two-year period were identified. Charts of these patients were reviewed to determine the quantity ingested per kilogram of body weight, method of decontamination used, the timing of decontamination, and the serum acetaminophen concentration obtained four hours after ingestion. RESULT: Charts of 455 patients met all requirements for inclusion. When emesis occurred within one-half hour after ingestion, mean serum acetaminophen concentration drawn four hours after ingestion was approximately half that in a control group that received no decontamination. Emesis had less impact when it was delayed further and had no demonstrable impact when it occurred more than 90 minutes after ingestion. CONCLUSION: Many factors must be considered when deciding if and by what method a given patient should receive decontamination. When delayed gastric emptying is not expected, emesis can at best decrease a toxic burden by half if it occurs early. Medical care givers must continue to scrutinize management practice to ensure that syrup of ipecac is given only in situations in which it is likely to make a difference in outcome and in which it is the most effective agent to achieve this goal.

Acetaminophen↗
PubMed1993

Deoxygenation-induced cation fluxes in sickle cells. III. Cation selectivity and response to pH and membrane potential.

Deoxygenation of sickle cells increases membrane permeability to Na, K, and Ca and contributes to cellular cation depletion. This study examines the physiological nature of the pathway that mediates deoxygenation-induced movements of monovalent cations. Deoxygenation-induced Rb influx was a linear function of external Rb concentration, with no evidence of saturation. Activation of the deoxygenation-induced pathway was fostered by alkaline pH (7.5), whereas ion movements via the activated pathway were optimal between pH 6.9 and 7.0 in cells incubated in media in which NO3 replaced Cl to eliminate KCl cotransport. The deoxygenation-induced pathway exhibited no selectivity among the alkali metal cations Li, Na, K, Rb, or Cs, but the monovalent organic cations tetramethylammonium, tetraethylammonium, and N-methylglucamine were excluded. Sickle cells incubated in low-Cl media (external Cl, 40 mM) to depolarize the membrane exhibited increased deoxygenation-induced K efflux and reduced Na influx. Cells treated with valinomycin to hyperpolarize the membrane showed increased deoxygenation-induced Na influx. These characteristics of the deoxygenation-induced transport pathway, linear concentration dependence, lack of cation selectivity, and response to membrane potential, argue against a carrier-mediated mechanism in favor of a diffusional process. The exclusion of small organic cations, however, suggests that factors other than ion size influence deoxygenation-induced permeability.

Anemia, Sickle Cell↗
PubMed1993

Experimental infection of Anopheles gambiae s.s., Anopheles freeborni and Anopheles stephensi with Plasmodium malariae and Plasmodium brasilianum.

Susceptibility to infection of 2 strains of Anopheles gambiae s.s., An. freeborni and An. stephensi, was determined for 2 closely related malaria parasites, Plasmodium malariae and P. brasilianum. Neither strain of An. gambiae supported development of oocyst densities as great as the other 2 anopheline mosquitoes. The ZAN strain of An. gambiae s.s. from Zanzibar was more susceptible to infection with the strain of P. malariae from Uganda than the G-3 strain of An. gambiae s.s. from The Gambia. All species and strains of mosquitoes supported complete development to the presence of sporozoites in the salivary glands.

Animals↗
PubMed1992

Reinforcement of immunity in Saimiri monkeys following immunization with irradiated sporozoites of Plasmodium vivax.

To determine the duration of immunity to Plasmodium vivax following immunization, six Saimiri sciureus boliviensis monkeys were vaccinated with irradiated sporozoites of P. vivax and challenged multiple times with sporozoites. Over a period of almost four years, complete protection from repeated challenge with infective sporozoites was demonstrated in one monkey; protection in two monkeys was obtained on eight of nine occasions, in one monkey on seven of nine occasions, in one monkey on six or nine occasions, and in one monkey on four of eight occasions. Five of six monkeys were protected against infection during the last six challenges. Inoculation with blood-stage parasites at the end of the trial indicated that all animals were susceptible to infection. These results suggest that protection against sporozoite challenge may be strongly reinforced by subsequent exposure to viable sporozoites.

Animals↗
PubMed1992

Development of a polymorphic strain of Plasmodium vivax in monkeys.

A strain of Plasmodium vivax from Thailand with a polymorphic repeat unit of the circumsporozoite protein was established in Saimiri sciureus boliviensis and 3 species of Aotus monkeys. All 11 attempts to transmit infection via sporozoite inoculation, 4 times to splenectomized S. sciureus boliviensis, 2 times to splenectomized Aotus nancymai, and 5 times to intact Saimiri monkeys, were successful. Anopheles freeborni, Anopheles stephensi, Anopheles dirus, and Anopheles gambiae mosquitoes were infected by feeding on parasitemic blood from a chimpanzee and an Aotus azarae boliviensis monkey. Our results indicate that this strain may be useful in antisporozoite vaccine trials.

Amino Acid Sequence↗