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Biomedical subjects

A Saul

Publications and source records attributed to A Saul.

At least 19 recordsLinked to original sources
PubMed1998

A novel single missense mutation identified along the RH50 gene in a composite heterozygous Rhnull blood donor of the regulator type.

Rare individuals who lack all of the Rh blood group antigens are called Rhnull and may be classified as "regulator" or "amorph" types. The suppression of Rh antigen expression for regulator types may be attributed to mutations of the RH50 gene, which is independent of the RH locus. The RH50 gene encodes a glycoprotein that interacts with the Rh proteins to form a functional complex within the red blood cell membrane. This report describes an RH50 gene mutation for a previously unclassified Rhnull donor. Sequencing cDNA clones from Rh50 mRNA revealed a single base change (G836A) yielding a missense and nonconservative mutation (Gly279Glu) within a predicted hydrophobic domain for this membrane protein. Genomic DNA studies using polymerase chain reaction (PCR) restriction analysis and sequencing showed that the Rhnull propositus was a composite heterozygote for this mutation, carrying two alleles with the A and G at nucleotide 836, respectively. In contrast, cDNA studies showed that only the A836 sequence was present, suggesting that the second allele with G836 was apparently silent (no transcript detected). Family studies showed that the mutant RH50 allele (836A) was inherited maternally, whereas the silent RH50 allele (836G) was from paternal transmission. These findings provide further evidence that rare but diverse genetic alterations may occur along the RH50 gene where the Rhnull syndrome of the regulator type occurs. The single amino acid change (Gly to Glu) provides insight into the critical value of these residues for assembly of the Rh antigen complex within the membrane.

Blood Donors↗
PubMed1998

Evolution and systematics of Anopheles: insights from a molecular phylogeny of Australasian mosquitoes.

Relationships among the genus Anopheles and its many sibling species-groups are obscure despite the importance of anophelines as the vectors of human malaria. For the first time, the interrelationships and the origin of Australasian members of the subgenus Cellia are investigated by a cladistic analysis of sequence variation within the mitochondrial cytochrome oxidase subunit II gene. Estimated divergence times between many Australasian and Oriental taxa predate the mid Miocene collision of Australasia and Southeast Asia. Phylogenetic analysis suggests that two-way exchanges with Oriental mosquitoes rather than only immigration may have been a characteristic of anopheline paleobiogeography in Australasia. The Australasian fauna is mostly included in a large clade. The medically important Punctulatus Group is monophyletic and appears derived from Oriental stock. Populations within this group from as far apart as Australia and Vanuatu were in contact in the recent past (i.e., 0.35-2.44 mya), supporting dispersal rather than vicariance explanations. Some support for the monophyly of the Myzomyia, Neomyzomyia, and Pyretophorus Series was found. However, the subgenera Anopheles and Cellia and the Neocellia Series are paraphyletic, but branch support at these taxonomic levels was poor. The COII gene shows promise for questions concerning alpha taxonomy but appears to be of limited use for resolving deeper relationships within the Anopheles.

Amino Acid Sequence↗
PubMed1998

Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malaria.

MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)-specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.

Adoptive Transfer↗
PubMed1998

Autoantibodies to autologous skin in guttate and plaque forms of psoriasis and cross-reaction of skin antigens with streptococcal antigens.

BACKGROUND: Psoriasis is a chronic disease of the skin that appears to be of autoimmune nature. It has a strong association with throat streptococcal infections, as well as with stressful events. Although many groups consider psoriasis to be a T-cell-mediated autoimmune disease, autoantibodies could also play a role in the development of this process. METHODS: In this work, we looked for autoantibodies to psoriatic skin in 21 psoriatic patients and four healthy donors (controls). The immunoperoxidase technique was used to look for autoantibodies in autologous sera in skin sections obtained from lesions or from healthy areas of the same patient, before and after immunoadsorption with a Streptococcus pyogenes extract. The skin biopsies were also analyzed with a pool of sera from mice immunized with the streptococcal extract. RESULTS: We found that all psoriatic patients had autoantibodies to antigens present in keratinocytes, whereas healthy subjects did not. These antibodies did not recognize epitopes on healthy skin from the same psoriatic patients or controls. Immunoadsorption of autologous sera removed the reactivity to antigens in skin lesions in all cases. Mouse anti-streptococcal sera recognized epidermal antigens present in lesional psoriatic skin, but not in healthy skin from psoriatic patients or controls. Deposits of immunoglobulin G (IgG) were not detected in the lesions. CONCLUSIONS: It seems that autoantibodies, although they do not appear to participate in the pathogenesis of psoriasis, are an important feature, and that skin antigens, which appear in lesional immature keratinocytes, cross-react with S. pyogenes and contribute to the autoimmune process in psoriasis.

Adult↗
PubMed1998

IgG antibody subclasses, tumor necrosis factor and IFN-gamma levels in patients with type II lepra reaction on thalidomide treatment.

A group of 9 Mexican lepromatous leprosy patients was studied at the beginning of a type II reaction (erythema nodosum leprosum, ENL) and after 1 or 2 months of thalidomide treatment. ENL patients at the onset of the reaction had slightly higher amounts of anti-Mycobacterium leprae IgG1 and IgG2 antibodies, compared to similar lepromatous patients that did not develop ENL. Neither these antibody levels nor IgM and the other IgG subclasses were importantly modified after thalidomide treatment. Serum TNF was significantly higher in the patients that developed ENL compared to those that did not develop the reaction. TNF levels were slightly decreased after 1 month of thalidomide treatment and significantly decreased after 2 months of treatment. Serum IFN-gamma was significantly lower in patients at the onset of ENL and was increased after 1 and 2 months of thalidomide treatment.

Adolescent↗
PubMed1997

Profile of Morong, Bataan, an area of low malaria endemicity in the Philippines.

A malaria study area in the Philippines is described. It consists of the municipality of Morong, Bataan on the Island of Luzon. In January 1992, the population was 19454 in 106 villages located on a narrow coastal plain, or in valleys of streams running from the mountainous interior. This is an area of low level but persistent seasonal transmission of malaria with approximately one thousand cases reported each year, mainly from February to July. In spite of the low level of malaria, it is apparently quite stable. The study site has been used to investigate parameters leading to stable malaria. Hypotheses tested were that there was substantial under reporting of cases; that there was strain specific immunity stabilising the incidence of malaria and that malaria transmission in this area is highly localised in small regions with a high enough malaria prevalence to account for the year to year stability. The study plan included cross sectional surveys of parasite prevalence and seropositivity, longitudinal surveys, passive case detection, entomological surveys, anthropological surveys to assess knowledge of malaria and documentation of the health-seeking behaviour of the population.

Adolescent↗
PubMed1997

Vector abundance and behaviour in an area of low malaria endemicity in Bataan, the Philippines.

The vectorial importance of known and potential vectors in Morong, Bataan, Philippines was assessed based on human and animal baited collections of adult mosquitoes and on larval collections. Anopheles flavirostris, the principal vector in the Philippines, was the most abundant among human landing catches, followed by An. maculatus sensu lato (s.l.). Both showed similar seasonal abundance with a peak during the early drier part of the year, which coincided with the peak in malaria cases. Both An. flavirostris and An. maculatus s.l. fed throughout the night with the broad peak of capture from 00:00 to 04:00 and from 22:00 to 00:00, respectively. The two species had similar parous rates (0.76 and 0.72, respectively) giving an average life span equivalent to four feeding cycles. Neither vector was abundant with average human landing rates on collectors of 0.6 and 0.4 mosquitoes per person per night, respectively over the study period. An. maculatus s.l. showed a stronger preference for outdoor feeding compared to An. flavirostris. An. maculatus s.l. was markedly zoophilic with a biting rate on water buffalo 50 times the human landing rate. An. flavirostris was less zoophilic with a corresponding ratio of 7.5. It was concluded that in this area, An. flavirostris is the principal vector. The combination of localised transmission, late night biting pattern and localised breeding sites of An. flavirostris suggest that the use of bed nets and environmental management are relevant control measures that can be implemented through community participation.

Animals↗
PubMed1997

Field epidemiological studies on malaria in a low endemic area in the Philippines.

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.

Adolescent↗
PubMed1997

Risk factors for infection with malaria in a low endemic community in Bataan, the Philippines.

The patterns of malaria morbidity and mortality can vary with the level of malaria transmission in a given area. We carried out two annual cross-sectional surveys in the hypoendemic malarious community of Morong, the Philippines, to examine epidemiologic and sociobehavioural risk factors for infection. In both surveys, the greatest risk of having malaria was associated with place of residence. For example, in the first survey, living in an area where more than 50% of the community had a high IFAT titer had an adjusted odds ratio (OR) of 33.7. A range of activities thought to be associated with risk were examined, but in the first survey, only frequent nocturnal visits to the forest were found to be a significant risk factor overall (adjusted OR; 2.65; 95% CI 1.48, 4.73), but this phenomenon was primarily observed among individuals residing in the lowest prevalence areas. In the second survey, where only the area with a relatively high prevalence of malaria was sampled, no association with activities was found. In this survey, significant factors associated with malarial infection were: being a migrant (adjusted OR 1.97; 95% CI 1.33, 2.92), being male (adjusted OR 1.63; 95% CI 1.10, 2.43) and age 30 years or less (adjusted OR 0.29 for age > 30 years; 95% CI 0.16, 0.52). The data suggest that in low-endemic communities like Morong, Bataan, control efforts should be primarily directed to focal areas identified by serology, particularly among migrants and among male young adults.

Adult↗
PubMed1997

Stability of malaria in a community in Bataan, the Philippines: prospects for control.

Malaria in Morong, Bataan, The Philippines, a municipality with relatively low level, but stable malaria is associated with small foci of relatively high endemicity. Although there is little association between age and symptomatic malaria, there is a reservoir of asymptomatic cases which are present throughout the year. Risk analysis suggests that the greatest risk factor in acquiring malaria depends on place of residence and not on occupation, including those associated with forest activities such as charcoal making. Foci of infection and the timing of symptomatic cases is closely correlated with breeding sites and abundance of adult Anopheles flavirostris. In spite of this close association, widely held views in the community that malaria is not related to mosquito transmission are likely to make better malaria control based on vector control difficult to sustain. Observation of treatment practices in the community and estimates of the number of apparently asymptomatic carriers from active case detection illustrate the importance of delayed treatment in providing a continuing reservoir of infection. These results highlight the need for improved early case detection and treatment.

Antibodies, Protozoan↗
PubMed1997

Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins.

An approach to mapping antigenic B cell epitopes within alpha-helical coiled coil proteins has been developed and applied to two proteins: Streptococcal M protein and C. elegans paramyosin protein UNC-15. Overlapping peptides derived from an alpha-helical coiled coil conformational epitope were embedded between helical flanking peptides derived from the completely unrelated GCN4 leucine zipper peptide. The resulting chimeric peptides exhibited helical propensity. Chimeric peptides were tested for antigenicity (recognition by antibody) or immunogenicity (production of appropriate antibody response). A conformational epitope within the Streptococcal M protein recognised by three mAbs spanned 12 residues. Analysis of chimeric peptides based on C. elegans UNC-15 has enabled fine mapping of the minimal B cell epitope recognised by monoclonal antibody NE1-6B2 to seven non-contiguous residues (spanning 15 residues); the footprint of contact residues involved in antibody recognition being restricted to the hydrophilic face of the helix and covering five helical turns. This chimeric peptide epitope when coupled to diphtheria toxoid was highly immunogenic in mice and antisera recognised the conformationally dependent native peptide epitope. This approach has the potential to map conformational epitopes and design minimal epitopes for use as vaccine candidates.

Amino Acid Sequence↗
PubMed1997

A putative Plasmodium falciparum exported serine/threonine protein kinase.

An 8kb gene coding for a putative serine/threonine protein kinase from Plasmodium falciparum has been cloned and sequenced. It is arranged in two exons: exon I is 2 kb and exon II is 5.6 kb. The gene codes for a large protein of 2510 amino acids. Antibodies raised against a fusion protein were used to localize the putative kinase. By immunofluorescence microscopy, it was found in the cytoplasm of infected red cells. By immunoelectron microscopy it was associated with membranous structures in the red cell and with the red cell membrane, particularly at parasite-induced knobs. This is the first putative protein kinase of P. falciparum to be exported from the parasite into its host cell.

Amino Acid Sequence↗