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P Perlmann

Publications and source records attributed to P Perlmann.

341 records · Page 19Linked to original sources
PubMed1965

Immunological studies in ulcerative colitis. II. "Colon" antigen and human blood group A- and H-like antigens in germfree rats.

Sera from patients with ulcerative colitis contain antibodies which hemagglutinate sheep red cells, sensitized with phenol-water extracts from. colon, cecum, or feces of germfree rats. Minor concentrations of such antibodies are also present in a certain fraction of normal human sera. Hemagglutination and hemagglutination inhibition experiments with human erythrocytes and with the rat extracts showed that the latter contained an antigen similar to human blood group A antigen. In contrast, a blood group B-like antigen could not be detected in these extracts. However, experiments with eel serum indicated that these extracts also contained an antigen similar to the H antigen of the human ABO system. Absorption of ulcerative colitis sera with human A(1) erythrocytes but not that with B or O erythrocytes gave, in a few cases, a slight reduction of the hemagglutinating titers against rat cecum-sensitized sheep erythrocytes. In contrast, this treatment considerably reduced such titers when found in sera from healthy persons or from patients with unrelated diseases. It could be concluded that the rat extracts also contained a "colon" antigen, detected with antibodies, present at elevated titers, in the sera of ulcerative colitis patients, but not in those of the controls. This colon antigen is immunologically distinct from the blood group antigens studied. Hemagglutination inhibition experiments indicated that A, H and colon antigen were widely distributed throughout the gastrointestinal tract of the germfree rats. The colon antigen was found to be enriched in the extracts from colon, cecum, and feces. Fluorescent antibody staining provided evidence that both the colon antigen and the A antigen were present in similar sites of the colon and cecum mucosa, particularly in goblet cells of the crypts, and in the mucus.

Animals↗
PubMedDate not supplied

A longitudinal study of antibodies to the Plasmodium falciparum antigen Pf155/RESA and immunity to malaria infection in adult Liberians.

118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults.

Adult↗
PubMedDate not supplied

Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria-endemic region of west Africa.

We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide-binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity.

Animals↗
PubMedDate not supplied

Serological diversity of antigens expressed on the surface of erythrocytes infected with Plasmodium falciparum.

We have studied the surface-antigen phenotypes of infected erythrocytes from children with acute falciparum malaria in the Punjab, Pakistan. Infected erythrocytes from 15 children and their homologous acute and convalescent sera, as well as hyperimmune sera from adults living in the same area, were used to analyse the serological diversity of parasite-associated antigens expressed on the surface of erythrocytes infected with Plasmodium falciparum. Analysis included agglutination, cytoadherence/inhibition of cytoadherence to melanoma cells, and rosette formation/disruption of rosettes formed between infected and non-infected erythrocytes. We found that isolate-specific antibodies were acquired by all children during convalescence and that there was a high degree of diversity of surface-antigen phenotypes. A majority of the sera either acquired or increased by 2- to 3-fold the capacity to inhibit cytoadherence and/or agglutinate the patient's own infected erythrocytes during convalescence and a strong correlation was found between these 2 activities. Hyperimmune sera from adults agglutinated and/or inhibited cytoadherence of many, but not all, of the isolates. Rosette formation was observed in 11 of the 15 isolates; 38% of the acute and 75% of the convalescent sera had anti-rosette activity on rosettes formed by the patient's own parasites. Among the isolates there was no correlation between rosette formation and binding of infected erythrocytes to melanoma cells. Our data provide good evidence that the children developed isolate-specific antibodies during convalescence from an acute attack of falciparum malaria and suggest that there was a high degree of heterogeneity of antigens expressed on the surface of infected erythrocytes.

Agglutination Tests↗
PubMedDate not supplied

IgE deposition in brain microvessels and on parasitized erythrocytes from cerebral malaria patients.

Postmortem brain tissues of 21 cerebral malaria cases were obtained in Myanmar and Vietnam. The tissues were examined by light microscopy and by an immunohistochemical method. Brain microvessels (capillaries and venules) were examined for the presence of immunoglobulins IgE and IgG, Plasmodium falciparum antigen, and parasitized erythrocytes (PRBC). Deposition of IgE, IgG, and P. falciparum antigen was observed in the microvessels from all specimens examined. Sequestered PRBC in the microvessels were positive for IgG in all 21 cases and for IgE in six cases. In the latter cases, the percentage of microvessels with sequestered PRBC was > 50%, with the frequency of IgE-positive cells ranging from 42% to 52%. In contrast, in five cases that were only weakly positive for IgE, the percentage of microvessels with sequestered PRBC was remarkably low (< 1%). These data indicate that the degree of deposition of IgE in microvessels and on PRBC from cerebral malaria patients correlated with that of PRBC sequestration. As IgE-containing immune complexes are known to induce local overproduction of tumor necrosis factor-alpha (TNF-alpha), a major pathogenic factor in cerebral malaria, IgE may contribute to the pathogenesis of this severe disease.

Adolescent↗
PubMedDate not supplied

Monoclonal antibodies against carcinoma cells of the human urinary bladder: immunohistochemical staining of tissues.

We have previously described the generation of mouse monoclonal antibodies (Mabs) directed to cell surface antigens of human bladder carcinoma. Based on experiments with cultured cells and a limited number of freshly isolated tissues, four distinct antigens were identified as being associated with this disease. In the present investigation, comprising the immunostaining of tissues of normal, malignant, and fetal origin, we have confirmed and extended the close association of these antigens with bladder cancer. Antibodies to all four antigens could clearly discriminate between malignant and normal uroepithelium. Two of the antibodies, SK4H-12 and 4E8, showed no additional reaction when tested with various adult tissues of normal or malignant origin. Antibodies to the remaining two antigens gave a positive staining of a few other tissue types.

Antibodies, Monoclonal↗
PubMedDate not supplied

Application in clinical epidemiology of new advances in immunology and molecular biology of malaria.

The first purpose was to study the sensitivity of a spot hybridization assay for P. falciparum with a DNA probe. This assay was compared with light microscopy for the detection of low-grade parasitemia. The second purpose was to study in clinically immune individuals the seroreactivity, against a newly identified P. falciparum antigen, deposited in the erythrocyte membrane during merozoite invasion (Perlmann et al., 1984). This antigen is considered to be a potential component in a future vaccine against the blood stage of the parasite. In a holoendemic village in Yekepa area, Northern Liberia, 28 adult men with a high degree of protective immunity against malaria, were shown to have repeatedly low-grade parasitemias of varying density. The spot hybridization assay with the DNA probe was highly sensitive in detecting parasitic infection. The sensitivity was comparable to that of the examination of a blood film for about 15 min by an experienced microscopist. The seroreactivity against Pf 155 antigen varied between a high positive titer to negativity in different subjects, but the reactivity was constant over a period of 15 months for each subject despite numerous new infections and comparable protective immunity against malaria infection.

Adult↗
PubMedDate not supplied

Radioimmunolocalisation of bladder tumors xenotransplanted in nude mice.

We have previously reported on the derivation of mouse monoclonal antibodies (Mabs), identifying several cell surface antigens selectively associated with cancer of the urinary bladder (TCC) (1-4). Three of these Mabs (4E8, SK4H and 8F4) have now been assessed for their ability to localise TCC-tumor xenografts in nude mice. The biodistribution of 125I-labeled intact Mabs as well as the corresponding Fab and F(ab')2 fragments from two of them were investigated in animals carrying TCC tumors or antigen negative control tumors. Using direct measurements of excised tissues, all three antibodies were seen to accumulate specifically in the TCC tumors, giving tumor to normal tissue ratios of between 3 and 20 depending on the Mab used and the time after injection. Antibody fragments were generally more efficient in their localisation, mainly due to a dramatic reduction in the blood background as compared to intact Ig. One of the antibodies, 4E8, was also employed for external imaging with gamma camera scintigraphy using 111In or 131I as tracers. Excellent visualisation of the tumor sites could be obtained both with Fab fragments and intact antibody within 12-24 hours after injection. As expected, background radioactivity was significantly lower with fragments than with whole molecules. 111In labeled antibodies appeared in all instances to be superior to the corresponding 131I conjugates. In conclusion, the present study indicates that the three anti TCC antibodies may become useful for the in vivo diagnosis of bladder cancer in man.

Animals↗
PubMedDate not supplied

Human bladder cancer associated antigens: evaluation of antigenicity in TCC tissues of different grades and in normal urothelium.

The expression of five antigens, associated with transitional cell carcinoma (TCC) of the urinary bladder on biopsies of tumors or normal urothelium, was studied by immunostaining with the corresponding monoclonal antibodies. Both tissue sections and single cell preparations were investigated with either indirect immunoperoxidase staining or immunofluorescence. All 5 antigens were expressed on the majority (70-90%) of sectioned tumor specimens from 44 TCC patients, and 4 of them were similarly expressed on single cell tumor preparations from 26 additional patients. However, in both types of preparation, the degree of expression of these antigens varied from scattered staining of less than 25% of the tumor cells to homogenous staining of all or almost all cells. This degree of expression varied individually for each of the antigens and was not related to the malignancy grade of the tumors. However, as most of the tumors were of grades II or III, no conclusions regarding the relationship of antigen expression to the aggressiveness of the tumors can be drawn. In any event, all tumors expressed at least one and mostly several of these antigens. Antigen expression on biopsies of normal bladder mucosa from TCC patients or on urothelial biopsies from patients with prostate hyperplasia was also observed on single cell specimens (34 patients) but not on sectioned material (9 patients). However, the frequency of positive specimens was much lower (4-20%). Moreover, the number of cells expressing one or, occasionally, several of the antigens in normal urothelium was small (usually less than 5%). Because of these marked differences in antigen expression between tumors and normal tissue, the results indicate that a combination of 3-5 of the antibodies used in this study may be suitable for diagnostic purposes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Ulcerative colitis.

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Antibodies↗