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Biomedical subjects

C L Morris

Publications and source records attributed to C L Morris.

At least 19 recordsLinked to original sources

Measurements of ultracold-neutron lifetimes in solid deuterium.

We present the first measurements of the survival time of ultracold neutrons (UCNs) in solid deuterium (SD2). This critical parameter provides a fundamental limitation to the effectiveness of superthermal UCN sources that utilize solid ortho-deuterium as the source material. These measurements are performed utilizing a SD2 source coupled to a spallation source of neutrons, providing a demonstration of UCN production in this geometry and permitting systematic studies of the influence of thermal up-scatter and contamination with para-deuterium on the UCN survival time.

Journal Article↗

Adaptation of a strain of Plasmodium vivax from India to New World monkeys, chimpanzees, and anopheline mosquitoes.

A strain of Plasmodium vivax from India was adapted to develop in splenectomized Saimiri boliviensis, Aotus lemurinus griseimembra, A vociferans, A. nancymai, A. azarae boliviensis, hybrid Aotus monkeys, and splenectomized chimpanzees. Infections were induced via the inoculation of sporozoites dissected from the salivary glands of Anopheles stephensi and An. dirus mosquitoes to 12 Aotus and 8 Saimiri monkeys; transmission via the bites of infected An. stephensi was made to 1 Aotus monkey and 1 chimpanzee. The intravenous passage of infected erythrocytes was made to 9 Aotus monkeys and 4 chimpanzees. Gametocytes in 13 Aotus monkeys and 4 chimpanzees were infectious to mosquitoes. Infection rates were markedly higher in mosquitoes fed on chimpanzees. PCR studies on 10 monkeys injected with sporozoites revealed the presence of parasites before their detection by microscopic examination. The India VII strain of P. vivax develops in Aotus and Saimiri monkeys and chimpanzees following the injection of parasitized erythrocytes, or sporozoites, or both. The transmission rate via sporozoites to New World monkeys of approximately 50% may be too low for the testing of sporozoite vaccines or drugs directed against the exoerythrocytic stages. However, the strain is highly infectious to commonly available laboratory-maintained anopheline mosquitoes. Mosquito infection is especially high when feedings are made with gametocytes from splenectomized chimpanzees.

Adaptation, Biological↗

Orofacial prosthesis design and fabrication using stereolithography.

The use of stereolithography for the manufacture of implantable prostheses is relatively new. Until now, its use with regard to mandibular resection has been to produce pre-operative models that allow more sophisticated planning of the contour and better preparation of the metallic framework to be implanted. This framework rejoins the sections of the mandible, returning some function, but providing no soft tissue support. Hence, the aesthetic results are not optimal. The aim of this study was to investigate the accuracy with which a stereolithographic model could be made to completely reunite both surfaces of the resected mandible and restore full contour. The design and fabrication of a mandibular prosthesis utilizing CAD/CAM technology and stereolithography is still in the early stages, but initial results indicate that with further research and better tools this could provide a new approach to mandibular resections, providing better aesthetic results.

Computer-Aided Design↗

Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys.

A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge.

Adjuvants, Immunologic↗

Adaptation of a chloroquine-resistant strain of Plasmodium vivax from Indonesia to New World monkeys.

The spread of chloroquine-resistant Plasmodium vivax from Papua New Guinea and Indonesia poses a serious health threat to areas of Southeast Asia where this species of malaria parasite is endemic. A strain of P. vivax from Indonesia was adapted to develop in splenectomized Aotus lemurinus griseimembra, Aotus vociferans, Aotus nancymai, and Saimiri boliviensis monkeys. Transmission to splenectomized Saimiri monkeys was obtained via sporozoites. Chemotherapeutic studies indicated that the strain was resistant to chloroquine and amodiaquine while sensitive to mefloquine. Infections of chloroquine-resistant P.vivax in New World monkeys should be useful for the development of alternative treatments.

Adaptation, Physiological↗

Deletion of the trichodiene synthase gene of Fusarium venenatum: two systems for repeated gene deletions.

The trichodiene synthase (tri5) gene of Fusarium venenatum was cloned from a genomic library. Vectors were created in which the tri5 coding sequence was replaced with the Neurospora crassa nitrate reductase (nit3) gene and with the Aspergillus nidulans acetamidase (amdS) gene flanked by direct repeats. The first vector was utilized to transform a nitrate reductase (niaD) mutant of F. venenatum to prototrophy, and the second vector was utilized to confer acetamide utilization to the wild-type strain. Several of the transformants lost the capacity to produce the trichothecene diacetoxyscirpenol and were shown by hybridization analysis to have gene replacements at the tri5 locus. The nit3 gene was removed by retransformation with a tri5 deletion fragment and selection on chlorate. The amdS gene was shown to excise spontaneously via the flanking direct repeats when spores were plated onto fluoroacetamide.

Amidohydrolases↗

Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19) of Plasmodium vivax in Saimiri boliviensis monkeys.

Saimiri boliviensis monkeys were immunized with the yeast-expressed recombinant protein yP2P30Pv200(19). The antigen consisted of the C-terminus (amino acid Asn1622-Ser1729) of the merozoite surface protein 1 of the Plasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P2 and P30) of tetanus toxin and six histidine residues for purification purposes were attached to the N- and C-termini, respectively. Four groups of five monkeys were given three immunizations at four-week intervals with either 250 microg of yP2P30Pv200(19) formulated with nonionic block copolymer P1005, 250 microg of antigen adsorbed to alum, 250 microg of antigen in phosphate-buffered saline (PBS), or PBS alone. Five weeks after the last immunization, each animal was inoculated with 100,000 parasitized erythrocytes of the Salvador I strain of P. vivax. Animals were splenectomized one week after challenge to increase parasite densities; after seven weeks of infection, animals were treated. Eighteen weeks later, the animals were rechallenged with the homologous parasite. Following the first challenge, three monkeys immunized with the antigen with P1005 were protected; no animals were protected from rechallenge. One monkey immunized with yP2P30Pv200(19) with alum was protected; no protection was seen after rechallenge. Two monkeys immunized with antigen alone were protected; none were protected from rechallenge. One control animal had a low parasite count following primary infection; none were protected against rechallenge. Adverse reactions were only observed with animals receiving P1005. It is proposed that splenectomy of the monkeys prevented adequate assessment of the efficacy of this antigen. Identification of a monkey host that supports high density parasitemia without splenectomy appears needed before further testing of blood-stage vaccines against P. vivax.

Adjuvants, Immunologic↗

Adaptation of the AMRU-1 strain of Plasmodium vivax to Aotus and Saimiri monkeys and to four species of anopheline mosquitoes.

A chloroquine-resistant strain of Plasmodium vivax (AMRU-1) from Papua New Guinea has been adapted to grow in 4 species of Aotus monkeys (Aotus lemurinus griseimembra, Aotus vaciferans, Aotus nancymai, and Aotus azarae boliviensis), hybrid Aotus monkeys, and Saimiri boliviensis monkeys. Whereas it was possible to infect Saimiri monkeys with this parasite by inoculation of parasitized erythrocytes, only 42% of Saimiri monkeys became infected, compared to 92% of Aotus monkeys attempted. Comparative mosquito feedings showed that only A. vociferans, A. l. griseimembra, and Saimiri boliviensis monkeys produced infections in mosquitoes. Oocysts were observed on the guts of the 4 species of mosquitoes used (Anopheles gambiae, Anopheles stephensi, Anopheles freeborni, and Anopheles dirus), but sporozoite transmission was effected only with the intravenous inoculation of sporozoites from An. dirus into an A. l. griseimembra monkey.

Adaptation, Biological↗

Intracranial pressure monitor placement by midlevel practitioners.

BACKGROUND: The timely treatment of patients with head injuries is affected by the availability and commitment of neurosurgeons. Use of midlevel practitioners (MLPs) may permit more efficient neurosurgical coverage. Intracranial pressure monitoring is among the most frequently used neurosurgical procedures. The purpose of this study was to examine the placement of intracranial pressure (ICP) monitors by MLPs. METHODS: Medical records and trauma registry data for a Level I trauma center were reviewed from December 1993 to June 1997. Patients who had ICP monitors placed were included. Patient data recorded were age, mechanism of injury, injury type, ICP monitor placement and length of placement, complications related to the ICP monitor, and outcomes. RESULTS: Two hundred ten patients had 215 monitors placed. ICP monitors were placed by neurosurgeons (105), MLPs (97), and general surgery residents (13), and remained in place a mean of 4 days. No major complications attributable to ICP monitor placement occurred; 19 minor complications (malfunction, dislodgment) were noted. Eleven monitors placed by neurosurgeons (10%), seven placed by MLPs (7%), and one placed by a resident (8%) had complications. CONCLUSION: ICP monitor placement by MLPs is safe. Use of MLPs may aid neurosurgeons in providing prompt monitoring of patients with head injuries.

Adolescent↗

Salvador II strain of Plasmodium vivax in Aotus monkeys and mosquitoes for transmission-blocking vaccine trials.

Infections with the Salvador II strain of Plasmodium vivax in Aotus lemurinus griseimambra monkeys were fed upon by Anopheles freeborni mosquitoes. Periods of mosquito infectivity were determined to establish a model system for the testing of transmission-blocking vaccines. The highest levels of mosquito infection were associated with the ascending asexual parasitemia after reaching 1,000/microl, and before the peak asexual parasite count. Sporozoite-induced infections were more infectious than were trophozoite-induced infections. Secondary episodes of parasitemia were also infectious, indicating the lack of development of naturally developing transmission-blocking immunity to this strain of P. vivax in splenectomized Aotus monkeys following single infections.

Animals↗

Attempts to transmit the N-3 strain of Plasmodium fieldi to Aotus monkeys.

Aotus lemurinus griseimembra monkeys inoculated with parasitized erythrocytes of the N-3 strain of Plasmodiumfieldi had transient low-density parasitemia. Exoerythrocytic stages of this strain of parasite were demonstrated in sections of liver from Aotus vociferans monkeys taken 8 days after the intravenous inoculation of sporozoites dissected from the salivary glands of Anopheles dirus mosquitoes; no blood-stage infections were observed.

Animals↗

Adaptation of a strain of Plasmodium vivax from Mauritania to New World monkeys and anopheline mosquitoes.

A strain of Plasmodium vivax from Mauritania was adapted to develop in Aotus lemurinus griseimembra, Aotus nancymai, Saimiri boliviensis, and hybrid Aotus monkeys. Infections were induced via the inoculation of sporozoites dissected from the salivary glands of Anopheles gambiae, Anopheles freeborni, and Anopheles stephensi mosquitoes or the intravenous passage of infected erythrocytes. Infections in 3 A. lemurinus griseimembra monkeys readily infected mosquitoes. Four lines of the Mauritania parasites have been stored frozen for further reference.

Adaptation, Physiological↗

Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation.

A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.

Adolescent↗

Protective immunity induced in squirrel monkeys with a multiple antigen construct against the circumsporozoite protein of Plasmodium vivax.

Saimiri boliviensis monkeys were immunized with a multiple antigen construct [(PvCS)2]2(P2)2 directed against the circumsporozoite protein of Plasmodium vivax or a combination of the multiple antigen construct with nonionic copolymer P1005, with P1005 and lipopolysaccharide, with muramyl tripeptide Mf-75, or with alum. Following intravenous challenge with 10,000 sporozoites of the Salvador I strain of P. vivax, 11 of the 26 monkeys were protected against patent parasitemia. Ten additional animals were partially protected. Following rechallenge of the 26 monkeys with 30,000 sporozoites of the homologous strain of parasite, four monkeys were totally protected and nine animals were partially protected.

Adjuvants, Immunologic↗

The Malayan IV strain of Plasmodium falciparum in Aotus monkeys.

Forty-nine infections with the Malayan IV strain of Plasmodium falciparum were induced in different species of Aotus monkeys. The parasite was shown to be infective to four different species of Aotus monkeys via the inoculation of parasitized erythrocytes. Sporozoite transmission was obtained to A. lemurinus griseimembra, A. vociferans, and hybrid monkeys with A. azarae boliviensis x A. nancymai and A. lemurinus griseimembra x A. nancymai parentage. Anopheles freeborni and An. stephensi mosquitoes fed readily on animals and through membranes; both supported the development of infective sporozoites. Markedly increased levels of mosquito infection were routinely obtained by membrane feeding, indicating the presence of serum factors inhibitory to infection. The Malayan IV strain appears suitable for blood-stage and transmission-blocking vaccine trials.

Animals↗

Studies on a primaquine-tolerant strain of Plasmodium vivax from Brazil in Aotus and Saimiri monkeys.

A nonimmune American acquired an infection of Plasmodium vivax Type 1 malaria in Brazil in 1994. After returning to the U.S.A., he had a primary attack followed by 3 relapses. The primary attack and first 2 relapses were treated with a standard regimen of chloroquine, followed by 14 days of primaquine (15 mg/day). Following the third relapse, the primaquine treatment was extended to 28 days. No further relapses occurred. The lack of response to primaquine by this strain may recommend it as a suitable candidate for chemotherapeutic study if it can be adapted to an animal model. Anopheles quadrimaculatus mosquitoes infected by feeding on the patient during the first relapse were used to establish the strain in Aotus and Saimiri monkeys. Monkeys supported well the development of long-lasting parasitemia. Anopheles freeborni, Anopheles stephensi, and Anopheles gambiae mosquitoes were readily infected by feeding on the monkeys and by membrane feeding on diluted blood. Monkey-to-monkey transmission was obtained via the bites of infected mosquitoes and the intravenous injection of sporozoites dissected from salivary glands. This parasite is designated as the Brazil I/CDC strain of P. vivax.

Animals↗

Infection of Anopheles freeborni mosquitoes on New World monkeys infected with the Uganda I/CDC strain of Plasmodium malariae.

Anopheles freeborni mosquitoes fed during 85 primary and 26 recrudescent infections of the Uganda I/CDC strain of Plasmodium malariae in Saimiri and Aotus monkeys were examined for the presence of oocysts. Of these, 42 primary and 14 recrudescent infections were infective. Mosquitoes were more frequently infected when fed upon A. lemurinus griseimembra animals. A retrospective examination indicated the greatest mosquito infectivity occurred before the maximum parasite count. Mosquito infection was highest 4, 5, and 6 days after the parasite count exceeded 1,000/microl. Overall, 98 of 304 positive lots (32.2%) had > or = 50% of the individual mosquitoes infected. In addition, lots of An. freeborni were fed through membranes on the blood of 34 monkeys. During the days following the parasite count reaching > or = 1,000/microl, feedings on the animals resulted in lower levels of infection than membrane feeding, thus extending the period of mosquito infection.

Animals↗

Adaptation of a strain of Plasmodium falciparum from a Montagnard refugee to Aotus monkeys.

A strain of Plasmodium falciparum from a Montagnard refugee was shown to produce large numbers of gametocytes in culture. Attempts were made to establish this strain in Aotus monkeys via trophozoite and sporozoite inoculation. The Montagnard S-1 strain was readily adapted to A. l. griseimembra monkeys via trophozoite inoculation. Other species of Aotus failed to support the development of high density parasitemia. None of 12 attempts to transmit the infection via sporozoites from Anopheles freeborni or An. dirus mosquitoes was successful; however, developing exoerythrocytic stages were demonstrated in hepatocytes of an A. lemurinus griseimembra monkey.

Adaptation, Physiological↗