Abstract. Complement receptor type 1 (CR1) on erythrocytes shows an inherited numerical polymorphism which correlates with a HindIII-RFLP (restriction fragment length polymorphism) of the CR1 gene in various populations. To investigate the relationship between CR1 density polymorphism and disease severity, we typed 185 Thai patients with acute falciparum malaria (55 severe and 130 uncomplicated) for their genotypes of this polymorphism. The level of expression of erythrocyte CR1 from 42 randomly selected patients was measured by enzyme-linked immunosorbent assay (ELISA). We observed a significantly higher frequency of homozygotes of the CR1 low density allele (LL) among the severe group as compared to the uncomplicated group (P ϭ 0.005). CR1 expression on erythrocytes from patients with the LL genotype was significantly lower than homozygotes with the high density allele (HH) (P Ͻ 0.0001) and heterozygotes (HL) (P ϭ 0.013). The results suggest that a genetically-determined low CR1 density on erythrocytes may be a risk factor for developing a more severe form of malaria in Thai subjects.

The effect of jasplakinolide (JAS), an actin-polymerizing and filament-stabilizing drug, on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum was examined. Jasplakinolide markedly decreased the parasitemia in a synchronized culture of P. falciparum strain FCR-3 in a time- and concentration-dependent manner. The decrease became evident at day 2 at concentrations of 0.3 micro M and above, and parasites finally disappeared at day 4. Giemsa-stained smears of P. falciparum-infected erythrocytes demonstrated that there was no effect on the development of schizonts from ring forms. Merozoites were released from the infected erythrocytes in a normal manner with and without JAS. However, there were no ring form-infected erythrocytes when JAS was administered, even after the release of merozoites. This indicates that the merozoites exposed to JAS failed to invade erythrocytes. The inhibitory effect of JAS on the parasitemia was reversed by the removal of the drug after exposure to 1 micro M of JAS for 1 day. Electron microscopy revealed that the merozoites treated with JAS showed a protrusion of the apical end which contained the microfilament structure. Immunoblot analysis indicated that the JAS treatment increased F-actin filaments of merozoites but had no effect on those of the trophozoites and schizonts. Therefore, this study demonstrated that JAS has an antimalarial activity.

SUMMARY Sporozoite invasion of mosquito salivary glands is critical for malaria transmission to vertebrate hosts. After release into the mosquito hemocoel,the means by which malaria sporozoites locate the salivary glands is unknown. We developed a Matrigel-based in vitro system to observe and analyze the motility of GFP-expressing Plasmodium berghei sporozoites in the presence of salivary gland products of Anopheles stephensi mosquitoes using temperature-controlled, low-light-level video microscopy. Sporozoites moved toward unheated salivary gland homogenate (SGH) but not to SGH that had been heated at 56°C for 30 min. We also investigated the origin of the attracted population. Attraction to SGH was restricted to hemolymph- and oocyst-derived sporozoites; salivary gland-derived sporozoites were not attracted to SGH. These data imply that sporozoites employ a chemotactic response to high molecular mass proteins or carbohydrate-binding proteins to locate salivary glands. This raises the possibility of utilizing anti-chemotactic factors for the development of mosquito transmission blocking agents.

BackgroundBrunner’s gland hamartoma is a rare tumor, predominantly found in the fifth to sixth decades of life. Generally, it is a single pedunculated polyp, rarely larger than 5 cm. Asymptomatic cases are found incidentally, but cases with a large polyp tend to have gastrointestinal bleeding and/or obstructive symptoms. Polyp size increases in a time-dependent manner, however, the growth mechanism is unknown. We report a Japanese male case in his mid-twenties with an over 6 cm sized polyp.Case presentationA 26-year-old man presented black stools and anemia. Endoscopic examination revealed a large pedunculated polyp at gastroduodenal junction. The polyp, subsequently resected by distal gastrectomy, was lobulated with random surface erosions and sized 6.4 × 3 cm. Histological examination revealed that the polyp arose from duodenal mucosa and was composed of hyperplastic Brunner’s glands in lobules separated by fibromuscular septa, associated with lymphocytic infiltrate and lymphoid follicles. No evidence of malignancy was found. Thus, the lesion was diagnosed as Brunner’s gland hamartoma. Further immunohistochemical studies indicated that gastric foveolar metaplasia is associated with surface epithelium covering upper two thirds of the polyp, showing immunohistochemical positivity for mucin 5 AC (MUC5AC). Below the metaplastic surface epithelium, Brunner’s glands had high proliferative activity (MIB-1 labeling index: 7.9%). The similar staining pattern was observed at surface erosive sites (MIB-1 labeling index in Brunner’s glands: 9%). On the other hand, surface epithelium in the lower side of the polyp still preserved intestinal nature, containing CDX2-positive nuclei and MUC2-positive goblet cells. Brunner’s glands below the surface epithelium with intestinal characteristics showed low proliferative activity (MIB-1 labeling index: 0.77%).ConclusionProliferative activity of Brunner’s glands was high at the sites with surface erosion and also below the epithelium showing gastric foveolar metaplasia. As gastric foveolar metaplasia occurs along with a mucosal repair process in the duodenum, mucosal damages underlay the hamartomatous proliferation of Brunner’s glands and eventually resulted in a formation of large polypoid mass in this case.