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Biomedical subjects

M Aikawa

Publications and source records attributed to M Aikawa.

At least 163 records · Page 9Linked to original sources
PubMed1993

Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta).

Six rhesus monkeys (Macaca mulatta) infected with Plasmodium coatneyi were studied for parasitized red blood cell (PRBC) sequestration in microvessels of the brain. The degree of PRBC sequestration is different in the cerebral, mid-brain, and cerebellar microvessels, with sequestration occurring preferentially in the cerebellum. This pattern resembles that of PRBC sequestration in cerebral and cerebellar microvessels in human falciparum malaria. The morphologic appearance of sequestered cells under light and electron microscopy as well as the PRBC sequestration pattern bolsters the contention that the rhesus monkey infected with P. coatneyi is an appropriate primate model for the experimental study of human cerebral malaria.

Animals↗
PubMed1993

Immunoglobulin complex deposits in Plasmodium falciparum-infected placentas from Malawi and Papua New Guinea.

Term placentas from 35 patients infected with Plasmodium falciparum were obtained in Malawi in southeast Africa and six term placentas from patients infected with P. falciparum were obtained in Wewak, Papua New Guinea, Melanesia. The placental tissues were examined by light microscopy and by an immunohistologic method to compare the pathologic changes of placentas in the two malaria-endemic countries. Using the number of parasitized red blood cells (PRBC) in intervillous spaces, pregnant women from Malawi with placental parasitemia were categorized into three groups. In the high PRBC group (> 20%, group I), there was no deposition of IgE in fetal blood vessels. In contrast, IgE was observed in fetal blood vessels of the intermediate PRBC group (1-10%, group II) and low PRBC group (< 1%, group III). In all six placentas from Papua New Guinean women, deposition of immune complexes, including IgE, was observed in the fetal blood vessels. All placentas with deposition of IgE in fetal blood vessels showed no sequestration of malaria parasites in intervillous spaces. Our data indicate that the amount of deposition of IgE in the placenta from women infected with P. falciparum is inversely correlated with the degree of parasitemia at that site.

Animals↗
PubMed1993

[A case of retroperitoneal fibrosis forming a pelvic tumor--a type of multifocal fibrosclerosis].

We experienced a case of retroperitoneal fibrosis with formation of a pelvic tumor. The patient was a 55-year-old female who showed right-side hydronephrosis on examination and was admitted to this department for consultation. Retrograde pyelography clearly showed that the hydronephrosis was due to lower ureteral obstruction resulting from a pelvic tumor. Ultrasound, CT and MRI showed a tumor adhering to the right posterior surface of the bladder, and it was thought that the tumor was probably malignant. Transdermal/transvesical needle biopsy and transvaginal needle biopsy showed a minimal invasion and allowed the diagnosis of retroperitoneal fibrosis to be made. Ureterolysis was not carried out, and the patient was treated with steroid monotherapy. She was begun on 30 mg of prednisolone, and administration was continued for approximately 3 months while gradually decreasing the dosage. On completion of administration, the intrapelvic tumor had completely disappeared, showing that treatment was markedly effective. The patient had a history of an orbital pseudotumor, and it was concluded that this was a rare case coming under the heading of multifocal fibrosclerosis.

Female↗
PubMed1993

[Proximal lower motor neuron syndrome associated with serum antibodies to asialo-GM1, GM1 and LM1].

A 31-year-old man had noticed slowly progressive weakness in his right upper limb girdle. On admission at age 32, fasciculation and muscle atrophy were observed in the right pectoralis major muscle. There was mild muscle weakness in the right triceps brachii muscle. The deep tendon reflexes were normal and the pathologic reflexes were absent. Sensory and autonomic nerve functions were intact. Needle EMG showed fibrillation potentials and positive sharp waves in the right pectoralis major, infraspinatus, extensor carpi radialis, extensor digitorum muscles, the bilateral sternocleidomastoideus and triceps brachii muscles. Motor nerve conduction studies revealed normal conduction velocities and distal latencies as well as no evidence of conduction block or abnormal temporal dispersion. Serum immunoelectrophoresis failed to detect an M protein. Thin-layer chromatography with immunostaining revealed that the serum contained auto antibodies which reacted with asialo-GM1, GM1 and LM1. This case must belong to "proximal lower motor neuron syndrome" proposed by Pestronk et al.

Adult↗
PubMed1992

Characterization of Plasmodium falciparum sporozoite surface protein 2.

Immunization of mice with Plasmodium yoelii sporozoite surface protein 2 (PySSP2) and circumsporozoite protein protects completely against P. yoelii. The amino acid sequence of PySSP2 suggested that the thrombospondin-related anonymous protein (TRAP) [Robson, K. J. H., Hall, J. R. S., Jennings, M. W., Harris, T. J. R., Marsh, K., Newbold, C. I., Tate, V. E. & Weatherall, D. J. (1988) Nature (London) 335, 79-82] is the Plasmodium falciparum homolog of PySSP2. We report data confirming that TRAP is P. falciparum SSP2 (PfSSP2). Murine antibodies against recombinant PfSSP2 identify a 90-kDa protein in extracts of P. falciparum sporozoites, recognize sporozoites and infected hepatocytes by immunofluorescence, localize PfSSP2 to the sporozoite micronemes by immunoelectron microscopy and to the surface membrane by live immunofluorescence, and inhibit sporozoite invasion and development in hepatocytes in vitro. Human volunteers immunized with irradiated sporozoites and protected against malaria develop antibody and proliferative T-cell responses to PfSSP2, suggesting that, like PySSP2, PfSSP2 is a target of protective immunity, and supporting inclusion of PfSSP2 in a multicomponent malaria vaccine.

Amino Acid Sequence↗
PubMed1992

Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.

The clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, Plasmodium falciparum. We now report that a primary P. falciparum-infected erythrocyte (parasitized red blood cell [PRBC]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor alpha (TNF-alpha)-activated human vascular endothelial cells is partially inhibited by antibodies to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive. PRBCs selected in vitro by sequential panning on purified adhesion molecules bind concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes. These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and may help delineate alternative adhesion pathways PRBCs use to modify malaria pathology.

Animals↗
PubMed1992

Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.

We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11-1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut.

Animals↗
PubMed1992

Localisation of hypoxanthine phosphoribosyl transferase in the malaria parasite Plasmodium falciparum.

The enzyme hypoxanthine phosphoribosyl transferase of the human malaria parasite Plasmodium falciparum has been located in parasites and parasite-infected erythrocytes by antibody probing. The probe was a polyclonal rabbit antiserum made against the parasite enzyme made in Escherichia coli. The enzyme is associated with membrane-bound compartments in merozoites and asexual blood parasites. In particular, indirect immunofluorescence studies reveal the enzyme localized in vesicle-like structures within the cytoplasm of the infected erythrocyte. This is the first time a P. falciparum protein of defined metabolic function has been tracked to a site outside the parasite cytosol. Studies on the targeting of the enzyme using a cell-free system suggests that the protein reaches its destination via a route different from the normal secretory pathway.

Amino Acid Sequence↗
PubMed1992

Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus.

Infection of the squirrel monkey, Saimiri sciureus, with several strains of Plasmodium falciparum leads in a proportion of animals to neurological symptoms with a fatal outcome. This first simian model for human cerebral malaria was studied with three strains of parasites, the uncloned Palo Alto(FUP-1) strain, the Palo AltoPLF3 clone MHB11, and the recently monkey-adapted P. falciparum strain IPC/RAY. Cerebral malaria could develop during primo infection of monkeys, whether the animals had been splenectomized or not. It did not occur in all animals and the appearance of neurological symptoms could not be predicted, as it was not related to the degree of parasitemia or duration of parasite infections.

Animals↗
PubMed1992

A monoclonal antibody directed against the sporozoite stage of Plasmodium vivax binds to liver parenchymal cells.

The circumsporozoite (CS) protein of malaria parasites is a major surface protein of the sporozoite stage. In the process of investigating the immunogenicity of this protein in the Plasmodium vivax complex, we found that a monoclonal antibody (mAb) directed against the CS protein of isolates of P. vivax recognizes New World monkey hepatocytes and human hepatoma cells HepG2A16 in Western blot and by immunoelectron microscopy. The mAb NVS3 binds to the amino acid sequence AGDR, which is also shared with the alpha 3 domain of the human and primate major histocompatibility complex class I. In addition, in vitro experiments suggest that the binding of the mAb NVS3 to hepatocytes from Saimiri monkey enhances the invasion or development of malaria sporozoites. These results form the basis for investigating the relationships between parasite surface proteins and host-cell receptors.

Amino Acid Sequence↗
PubMed1992

Alpha-tubulin II is a male-specific protein in Plasmodium falciparum.

The tubulin gene family in Plasmodium falciparum consists of one beta-tubulin and two alpha-tubulin genes (alpha-tubulin I and II). We present here data indicating that alpha-tubulin II is expressed only in male sexual stage parasites. An IgM mAb, 5E7, specifically reacted with stage III (day 4-5) through mature (day 10-11) male gametocytes and with emerging, exflagellating, or freely moving male gametes. No reactivity was detected in female gametocytes, female gametes, sporozoites, or asexual parasites. mAb 5E7 also specifically recognized male gametes of the avian parasite, Plasmodium gallinaceum, and immunoblotted a 50 kDa protein in extracts of male gametes from both species. This 50 kDa antigen was localized by immunoelectron microscopy to axonemes of male gametes in a pattern similar to that obtained with anti-alpha- and anti-beta-tubulin antibodies. Furthermore, mAb 5E7 specifically reacted with recombinant alpha-tubulin II protein obtained using the PCR-amplified alpha-tubulin II gene from a gametocyte-specific cDNA library. The sex-specific expression of alpha-tubulin II and its localization to axoneme of the male parasite suggest a role for this molecule in the morphologic changes that occur during exflagellation and in the motility of the parasite. alpha-Tubulin II and mAb 5E7 may prove useful tools in studies of the biology of sexual stage differentiation and development in P. falciparum in addition to the general understanding of post-translational modifications of tubulin isoforms.

Animals↗
PubMed1992

Plasmodium falciparum-infected erythrocyte receptor(s) for CD36 and thrombospondin are restricted to knobs on the erythrocyte surface.

Adherence of Plasmodium falciparum-infected RBCs (PRBC) to endothelial cells causes PRBC sequestration in cerebral microvessels and is considered to be a major contributor to the pathogenesis of cerebral malaria. Both CD36 and thrombospondin (TSP) are glycoproteins that mediate PRBC adherence to endothelial cells in vitro. Because they are both expressed on the surface of endothelial cells, they probably contribute to PRBC sequestration and vascular occlusion in vivo. By applying affinity labeling of receptor binding sites with purified ligands, we showed for the first time that both CD36 and TSP can bind independently to the PRBC surface and that the PRBC receptor(s) for CD36 and TSP are localized specifically to the electron-dense knob protrusions of the PRBC surface. These findings may help in efforts to develop a malaria vaccine to prevent cerebral malaria.

Affinity Labels↗
PubMed1992

Characterization of a Plasmodium falciparium mutant that has deleted the majority of the gametocyte-specific Pf11-1 locus.

We identified a gametocyte-specific protein of Plasmodium falciparum called Pf11-1 and provide experimental evidence that this molecule is involved in the emergence of gametes of the infected erythrocyte (gametogenesis). A mutant parasite clone, which has deleted over 90% of the Pf11-1 gene locus, was an important control to establish the gametocyte-specific expression of the Pf11-1. Molecular analysis of the Pf11-1 deletion indicates that it is presumably due to a chromosome breakage with subsequent 'healing' by the addition of telomeric heptanucleotides. Moreover, similar DNA rearrangements are observed in most of the laboratory isolates during asexual propagation in vitro.

Animals↗
PubMed1992

A study on the pathogenesis of human cerebral malaria and cerebral babesiosis.

Cerebral complications are important, but poorly understood pathological features of infections caused by some species of Plasmodium and Babesia. Patients dying from P. falciparum were classified as cerebral or non-cerebral cases according to the cerebral malaria coma scale. Light microscopy revealed that cerebral microvessels of cerebral malaria patients were filled with a mixture of parasitized and unparasitized erythrocytes, with 94% of the vessels showing parasitized red blood cell (PRBC) sequestration. Some degree of PRBC sequestration was also found in non-cerebral malaria patients, but the percentage of microvessels with sequestered PRBC was only 13%. Electron microscopy demonstrated knobs on the membrane of PRBC that formed focal junctions with the capillary endothelium. A number of host cell molecules such as CD36, thrombospondin (TSP) and intercellular adhesion molecule I (ICAM-1) may function as endothelial cell surface receptors for P. falciparum-infected erythrocytes. Affinity labeling of CD36 and TSP to the PRBC surface showed these molecules specifically bind to the knobs. Babesia bovis infected erythrocytes produce projections of the erythrocyte membrane that are similar to knobs. When brain tissue from B. bovis-infected cattle was examined, cerebral capillaries were packed with PRBC. Infected erythrocytes formed focal attachments with cerebral endothelial cells at the site of these knob-like projections. These findings indicate that cerebral pathology caused by B. bovis is similar to human cerebral malaria. A search for cytoadherence proteins in the endothelial cells of cattle may lead to a better understanding of the pathogenesis of cerebral babesiosis.

Animals↗
PubMed1992

Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria.

Although several animal models for human cerebral malaria have been proposed in the past, none have shown pathological findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)-infected rhesus monkeys. Our study demonstrated parasitized erythrocyte (PRBC) sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral microvessels of these monkeys. This is similar to the findings seen in human cerebral malaria. Cerebral microvessels with sequestered PRBC were shown by immunohistochemistry to possess CD36, TSP and ICAM-1. These proteins were not evident in cerebral microvessels of uninfected control monkeys. Our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria.

Animals↗
PubMed1992

Purification and in vitro selection of rosette-positive (R+) and rosette-negative (R-) phenotypes of knob-positive Plasmodium falciparum parasites.

We have developed methods for in vitro selection of Plasmodium falciparum parasites that bear knob protrusions (K+) and are either of the rosette-positive (K+R+) or rosette-negative (K+R-) phenotypes. Cryopreserved parasites from spleen-intact Aotus monkeys that were K+, C32 cell adherence-positive (C+), CD36 adherence-positive, and R- with Aotus erythrocytes were adapted to continuous growth in human erythrocytes, and selected initially for adherence to C32 melanoma cells. In the absence of independent selection for rosettes, K+R-C+ parasites were produced that adhered to both C32 cells and CD36. Without selection for the C+ phenotype, K+R-C- parasites eventually predominated in such cultures. The R+ parasites were selected using differences in sedimentation behavior of rosette-infected cells versus non-rosette-infected cells. Methods were devised for selection of the R+ or R- phenotypes and for the purification of R+ or R- infected cells of high parasitemia that were suitable for molecular studies. With the repeated selection for K+R+ parasites, we were able to maintain the K+R+ phenotype for several months in vitro. These methods will allow systematic study of the molecular basis of the K+R+ and K+R- phenotypes.

Animals↗
PubMed1992

A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys.

A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria.

Animals↗