Screening for glaucoma in general practice.
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Family Practice↗
Biomedical subjects
A Aggarwal
Publications and source records attributed to A Aggarwal.
Occurrence of systemic autoimmune disorders & autoantibodies in house-hold contacts of patients with systemic lupus erythematosus.
Household contacts of 22 randomly selected patients with systemic lupus erythematosus (SLE) were screened for autoimmune diseases and autoantibodies. Thirty nine consanguineous and 17 nonconsanguineous household contacts were studied. In the first group symptomatic SLE was seen in 5 per cent, rheumatoid arthritis in 2.5 per cent, antinuclear antibody (ANA) in 10 per cent and rheumatoid factor (RF) in 5 per cent while anti-dsDNA, anti-nRNP and anti-Sm antibodies were not detected in any individual. The second group showed total absence of any marker of autoimmunity. In normal controls only RF was detected in 3 per cent. The occurrence of markers of autoimmunity only in consanguineous household contacts of patients with SLE further confirms the recognised role of genetic factors in the etiology of SLE.
Aged↗
Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells.
Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.
Animals↗
A heat shock protein gene in Giardia lamblia unrelated to HSP70.
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Amino Acid Sequence↗
Pulmonary artery occlusion pressure is not accurate immediately after cardiopulmonary bypass.
Elevated pulmonary vascular resistance (PVR), differential cardiac dynamics, and increased lung water following cardiopulmonary bypass (CPB) have been proposed as limitations to the accuracy of the pulmonary artery occlusion pressure (PAOP) in estimating left ventricular preload. A prospective study of 22 patients undergoing elective myocardial revascularization is described wherein PAOP was compared with directly measured left atrial pressure (LAP). The reliability of PAOP to estimate LAP in the hour immediately following CPB and at 1, 4, 8, and 12 hours post-CPB was examined with repeated measures analysis of variance. Relationships between the PAOP-LAP difference and PVR, core temperature, arterial CO2 tension, and right and left ventricular stroke work indices (RVSWI, LVSWI) were tested by linear regression analysis. There was greater variability in measurements at 15, 30, and 45 minutes immediately after CPB, demonstrated by a pooled correlation coefficient of 0.73 versus 0.90 in the postoperative period. The degree of discrepancy between PAOP and LAP lessened with time. There was no determinable relationship of the PAOP-LAP gradient to PVR, level of PCO2, temperature, RVSWI, or LVSWI. Potential sources of discrepancy include airway pressure effects, position of the measuring catheters, positive end-expiratory pressure, infusion of protamine sulfate, extremes of pulmonary artery pressures, and effects of an open pericardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Evaluation of vaccines designed to induce protective cellular immunity against the Plasmodium yoelii circumsporozoite protein: vaccinia, pseudorabies, and Salmonella transformed with circumsporozoite gene.
In an attempt to induce a protective cytotoxic T-cell mediated immunity against sporozoites of Plasmodium yoelii, the gene encoding the P. yoelii circumsporozoite (CS) protein was engineered into three live vectors: vaccinia, attenuated pseudorabies, and attenuated Salmonella typhimurium. Balb/c mice were immunized with 1-4 doses of 10(8) pfu of the vaccinia construct (IP), 3 doses of 10(5), 10(6) or 10(7) pfu of pseudorabies construct (IV), and 3 doses of 10(9) salmonella transformants (orally). In the case of vaccinia and pseudorabies constructs, an excellent immune response was obtained as measured by antibodies to sporozoites. No protection or delay in prepatent period was seen in any of the experimental animals when challenged with 200 (vaccinia, pseudorabies) or 100 (salmonella) sporozoites, although mice immunized with irradiation-attenuated sporozoites were consistently protected against challenge with greater than 10(4) sporozoites. Since other vaccinia, pseudorabies, and salmonella CS constructs have been shown to induce cytotoxic T lymphocytes (CTL) against the CS protein, it is likely that CTL against the CS protein were induced during these studies. It is currently unclear if the vaccines did not induce the appropriate CTL or inadequate numbers of CTL, or if CTL against the P. yoelii CS protein are inadequate to protect against sporozoite challenge.
Animals↗
Cysteine-rich variant surface proteins of Giardia lamblia.
Surface antigenic variation was previously demonstrated in vitro and in vivo using Giardia lamblia isolate WB. To determine whether other isolates undergo similar changes, isolates GS and N were cloned and exposed to cytotoxic anti-isolate sera or monoclonal antibodies (MAbs) specific to particular surface antigen. The surviving Giardia (progeny) and clones showed different surface antigens as judged by resistance to cytotoxicity, loss of antigens determined by surface radiolabeling, and failure of MAbs to recognize epitopes by immunoprecipitation. The major varying surface antigens incorporate large amounts of [35S]cysteine compared to [35S]methionine. Surface antigenic variation occurs commonly in Giardia isolates, and the major surface antigens appear to comprise a family of cysteine-rich proteins.
Animals↗
Inheritance and phenotypic expression of a t(7;9)(q36;q34)mat.
We describe a subtle familial chromosome rearrangement which involves 7q36 and 9q34. The clinical manifestations of 3 apparently balanced individuals with presumed identical translocation breakpoints are presented. In addition, the phenotypes of 2 cytogenetically unbalanced sibs in the same nuclear family are compared.
Adolescent↗
Characterization of a 29.4-kilodalton structural protein of Giardia lamblia and localization to the ventral disk [corrected].
The amino acid sequence of a 29.4-kilodalton [corrected] structural protein located in the ventral disk and axostyle of Giardia lamblia was determined. Clone lambda M16 from a mung bean expression library in lambda gt11 expressed a fusion protein recognized by three different isolate-specific antisera and sera from G. lamblia-infected gerbils. One of the three EcoRI fragments (M16; 1.26 kilobases) encoded the recognized protein. Sequence analysis revealed a single open reading frame of 813 base pairs. Two areas showed conservation of the positions of some amino acids. The abundance of arginine, glutamic acid, and threonine was increased. Two potential alpha-helical regions were deduced in the regions of repeats. Antisera to the M16 fusion protein reacted specifically with internal components of the ventral disk and axostyle, as well as Giardia fractions enriched for ventral disk structural proteins. An identical protein was recognized in different isolates by anti-M16, and a single identical band was recognized in Southern blots using the M16 1.26-kilobase fragment as a probe. Therefore, the 29.4-kilodaltion [corrected] protein appears to be highly conserved compared with variant surface proteins.
Amino Acid Sequence↗
Antigenic variation in Giardia lamblia.
Clones of the WB isolate of Giardia lamblia were exposed to cytotoxic mAb 6E7 which reacts with a 170-kDa surface Ag. Surviving progeny occurred at a frequency of about 1 in 1000 and were resistant to the effects of mAb 6E7. Analysis of progeny and clones of these progeny by surface radiolabeling, surface immunofluorescence, and Western blotting failed to detect the 170-kDa Ag. Loss of this Ag was associated with the appearance of a series of new surface Ag. A cytotoxic mAb (5C1) was produced to one of the newly appearing antigens (approximately equal to 64 kDa) and Giardia resistant to the cytotoxic effects of 5C1 isolated. Neither the approximately equal to 64 kDa nor the 170 kDa Ag were present and were replaced by a second series of new Ag. These studies clearly establish the loss and subsequent replacement of two antigenically distinct epitopes on Giardia derived from a single organism.
Animals↗
Antigenic variation of a cysteine-rich protein in Giardia lamblia.
The WB isolate of Giardia lamblia expresses a cysteine-rich 170-kD surface antigen (CRP170) that undergoes antigenic variation. An (6E7), cytotoxic for isolates expressing CRP170, was used in another study to select antigenic variants from clones of the WB isolate of Giardia. CRP170 was replaced by surface-labeled bands ranging in size from approximately 50 to 170 kD. In this study, mAb 6E7 was used to isolate a 1-kb portion of the CRP170 gene (M2-1) from a lambda gt 11 expression library. The M2-1 clone hybridized to a 5.4-kb transcript from isolates expressing CRP170 but did not hybridize to RNA from antigenic variants. Evidence was found for frequent rearrangements at the CRP170 gene locus. DNA sequencing of the M2-1 clone revealed the presence of long tandem repeats. The putative amino acid sequence of M2-1 reveals a 12% cysteine content, and CRP170 is readily labeled in vivo with cysteine.
Amino Acid Sequence↗
Antigenic variation of Giardia lamblia in vivo.
A single Giardia lamblia trophozoite can give rise in vitro to G. lamblia with varying surface antigens. To determine whether antigenic variation also occurs in vivo, gerbils were inoculated with defined G. lamblia clones and the surface antigens of the intestinal trophozoites were studied at different times during the infection. The proportion of monoclonal antibody 6E7-reacting trophozoites from WB C1-6E7S-inoculated gerbils had decreased significantly by day 3 postinoculation, indicating the presence of a heterogeneous population. On day 7, the 170-kilodalton antigen was no longer present and was replaced by a variety of antigens, including a major protein of 92 kilodaltons. With the exception of isolates from gerbils inoculated with WB A6-6E7S, the banding patterns of G. lamblia isolated from gerbils on day 7 or later were the same regardless of the clones used for inoculation. These studies show that G. lamblia changes its surface antigen(s) in vivo within 7 days following inoculation and appears to maintain the same set of surface antigens during the course of infection.
Animals↗
Giardia lamblia: RNA translation products.
The in vitro translation products of two different human isolates of Giardia lamblia, WB 2x and GS/E, were compared in order to determine common protein constituents and to identify proteins recognized by the infected host. Multiple polypeptides ranging from 20 to 185 kDa were synthesized using a rabbit reticulocyte cell-free translation system and although most were identical some differences were noted. GS/E compared to WB 2x showed different polypeptides of 23.5, 24.5, 26.5, 27.5, 32.5, 33.5, and 41 kDa. Some of these polypeptides were antigenic and were immunoprecipitated with anti-isolate antiserum from experimentally infected humans and gerbils. The sera of humans experimentally infected with isolate GS/M recognized a 24-kDa polypeptide from WB 2x and 23.5- and 24.5-kDa polypeptides from GS/E in vitro translation products. Sera from WB 2x- and GS/E-infected gerbils recognized 74- and 24-kDa polypeptides present in WB 2x translation products and 23.5-, 24.5-, 32.5-, 33.5-, and 74-kDa polypeptides when GS/E in vitro translation products were used. These studies identified both unique and common antigens in two different Giardia isolates and they may be of use in the serologic diagnosis of giardiasis and characterization of Giardia isolates.
Animals↗
Comparison of two antigenically distinct Giardia lamblia isolates in gerbils.
Previous studies established that some isolates of Giardia differ antigenically. In order to determine if antigenic differences resulted in altered biological behavior of host immune responses, two antigenically distinct isolates, WB and GS-E, were used to infect gerbils, and the course of infection, resistance to reinfection, and host humoral responses were measured. Maximum numbers of trophozoites were recovered on day 14 from the intestine of gerbils infected with both isolates, but by day 28, 75% of WB-infected gerbils were free of infection, while GS-E-infected animals continued to be infected until day 42. After curative metronidazole therapy, animals were challenged with the homologous or heterologous isolates. Gerbils previously infected with WB were resistant to challenge with WB and GS-E, while previously GS-E-infected gerbils were more resistant to challenge with the homologous isolate. Antibody responses were measured by ELISA to both surface and cytosol antigens and by IFA to the surface of Giardia. By IFA there was a greater reactivity using the homologous isolate, but with ELISA this was not as apparent. Complement independent cytotoxicity of sera was additionally tested against both isolates. Sera from WB-infected gerbils were cytotoxic to both WB and GS-E whereas sera from GS-E-infected gerbils were cytotoxic to GS-E only. These studies demonstrate that Giardia possessing different surface antigens have different patterns of infection and induce qualitatively and quantitatively different immune responses. Cytotoxicity of sera, most likely antibodies, correlated best with the development of resistance.
Animals↗
Tropical splenomegaly syndrome and the role of chloroquine prophylaxis.
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Adult↗
Lack of cellular cytotoxicity by human mononuclear cells to Giardia.
Cytotoxicity of mononuclear leukocytes (MNL) to Giardia lamblia was compared by using two techniques. The first method assessed the viability of surviving Giardia directly by culturing and the second method measured release of incorporated [3H] thymidine. Cytotoxicity, as measured directly by culturing and visual assessment, showed that the numbers of surviving Giardia decreased over time whether cultured with or without MNL but that Giardia survived significantly better in the presence of MNL at 18 hr (21.8 +/- 8.3% with MNL compared with 3.4 +/- 1.5% without MNL). Release of [3H]thymidine increased whether Giardia were cultured with or without MNL and although there was a tendency for increased release with MNL, there was no significant difference. Dead labeled Giardia released significantly more label in the presence of MNL than without MNL, suggesting that MNL cause release of [3H]thymidine after phagocytosis. The thymidine release assay therefore does not measure spontaneous cytotoxicity of MNL to Giardia.
Animals↗
Cytotoxicity of monoclonal antibodies to a subset of Giardia isolates.
Previous studies showed that some Giardia lamblia isolates differ and can be categorized on the basis of their DNA banding patterns after digestion with endonuclease restriction enzymes, surface antigens, and excretory-secretory (E-S) products. In the present study, monoclonal antibodies (McAb) were produced that reacted with one specific group of Giardia isolates. These McAb recognized a 170,000 dalton antigen, which was present on the surface of these Giardia and released into the medium as an E-S antigen. This antigen was previously characterized and found to distinguish this subgroup of Giardia. In addition, these McAb were cytotoxic only for this subgroup of Giardia. Immobilization occurred immediately, and killing was documented by 7 min. The mechanism(s) of killing remains unknown but was shown to be complement independent and did not occur with Fab'. These McAb identifies certain isolates and can be used to type Giardia.
Animals↗