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Biomedical subjects

K Ulrich

Publications and source records attributed to K Ulrich.

At least 19 recordsLinked to original sources

Competition ELISA using a human monoclonal antibody for detection of antibodies against human immunodeficiency virus type 1.

A novel competition ELISA for detection of antibodies against HIV-1 was developed. The assay is based on competition at the single epitope level and utilises a human monoclonal antibody and an E. coli-produced fragment of the transmembrane glycoprotein gp41. The sensitivity of the assay was 100% in tests on 247 serum samples obtained from 219 individuals previously shown to be HIV-1 antibody positive by both conventional indirect ELISA and the immunoblotting test. The patients represented various clinical and immunological stages of HIV-1 infection. Likewise, the specificity of the assay was 100% in tests on 105 serum samples from normal individuals previously tested negative by indirect ELISA. Further, among 105 serum samples selected due to consistent false positive reactions in the indirect ELISA only 2 samples (1.9%) demonstrated false positive reactions in the competition ELISA, i.e. 98.1% specificity. Finally, only 2 of 57 (3.5%) serum samples from HIV-2 infected individuals showed positive reactions in the assay, while 54 (94.7%) had absorbance values similar to the negative controls. These results demonstrate that human monoclonal antibodies may form the basis for highly sensitive and specific assays for detection of antibodies to HIV-1.

AIDS Serodiagnosis

Characterization of a new malignant human T-cell line (PFI-285) sensitive to ascorbic acid.

A new malignant human T-cell line-labelled PFI-285-has been isolated from a boy with malignant lymphoma. Morphologically, the cells had characteristics of malignant lymphoid cells. The cells presented surface antigens as early cortical lymphocytes and proliferated non-adherently as single cells, independent of T-cell growth factor (IL-2), in liquid culture. The cells had undetectable levels of receptors for IL-2, were not clonogenic in soft agar, but did form tumors in nude mice. Their establishment and continuous growth in vitro was dependent on the number of cells inoculated and on the growth medium used. Cytogenetic alteration, HTLV-1 or reverse transcriptase activity were not detected. The production of known T-cell derived lymphokines such as IL-2, B-cell growth factor(s), alpha-interferon or granulocyte/macrophage colony stimulating or inhibiting factor(s) was not detected. The cells had 5-8% natural killer (NK)-cell activity against NK-cell sensitive target cells (K562) and were not sensitive for NK cells. A most unusual characteristic was the pronounced sensitivity of the cells to ascorbic acid. Concentrations down to 50 mumol/l killed the cells within hours.

Adolescent

Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody.

A human monoclonal antibody, 41-7 [immunoglobulin G1(kappa)], directed against the transmembrane glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV-1) has been produced by direct fusion of lymph node cells from an HIV-1-infected individual with a human B-lymphoblastoid cell line. The minimal essential epitope for 41-7 was mapped to a conserved seven-amino acid sequence, N-CSGKLIC-C, located within the N-terminal part of gp41. Antibodies blocking the binding of 41-7 could be detected in the serum of all HIV-1-infected individuals tested, irrespective of the stage of the infection. The epitope is located externally to the plasma membrane, and it is accessible to antibody in the native conformation of the glycoprotein. Despite this, no neutralizing activity of 41-7 could be demonstrated in vitro. These data indicate, directly and indirectly, that this immunodominant epitope on gp41, although exposed on the viral surface, elicits antibodies lacking antiviral activity and, hence, should be avoided in future vaccine candidates.

Amino Acid Sequence

[Freckles and dysplasias of the eyebrows as indicators for genetic abnormalities of the development of the teeth and the jaws].

For the first time the frequency of freckles and of dysplasias of the eyebrows was examinated in 756 pupils. The percentage of the freckles was 21, and of the dysplasias of the eyebrows 28.5 in both sexes. The following examination of 287 orthodontic patients (66 males with hypodontia, 60 males with normal number of the teeth; 92 females with hypodontia, 69 females with normal number of the teeth) has demonstrated the high significance of incidence of freckles and of dysplasias of the eyebrows in patient with hypodontia. This phenomenon is important, because extraoral stigmatas can indicate to disturbances of the development of teeth and also to anomalies of the number of the teeth.

Anodontia

Antibodies against the major core protein p24 of human immunodeficiency virus: relation to immunological, clinical and prognostic findings.

In 79 homosexual men positive for antibody to human immunodeficiency virus (HIV), the titer and avidity of p24 antibody was determined by an indirect ELISA and the serum tested for the presence of HIV antigen. Results were examined for a possible correlation with clinical, immunological and prognostic findings. High titers and low avidity of p24 antibodies correlated significantly with a normal pokeweed mitogen response, early lymph node changes, and an asymptomatic and stable clinical condition. In HIV antigen negative patients, low titers and high avidity of p24 antibodies correlated significantly with a progressive clinical condition. The finding of primarily high avidity antibodies against p24 antigen in patients with more advanced immunodeficiency indicates that a decline of p24 antibodies during the clinical course of HIV infection may not be explained exclusively by an increased production of viral proteins.

Acquired Immunodeficiency Syndrome

[Isolated canine aplasia in monozygotic twins].

This article describes isolated aplasia of the upper canines with retained deciduous canines in identical female twins. The twins are also concordant in some ectodermal stigmata. As a result of investigating other members of the family it appears that aplasia of the canines is due to a specific autosomal dominant gene.

Adolescent

HIV neutralizing antibodies: development and association with HIV related disease.

Serum neutralization was measured in 72 sera collected during a 5.5-year period from 10 HIV infected individuals. Neutralizing antibodies (NA) were present in all sera. NA titers ranging from greater than 40 to greater than 640 were detected in sera from 4 patients, who all remained healthy and further an increase with time of NA was observed in these 4 patients. Progression to disease was observed in 3 persons with NA titers less than or equal to 40 who also lacked or lost anti-gag antibodies. Two of these patients were HIV antigenaemic prior to development of disease, whereas antigen was not detected in the remaining 7 healthy persons. A weak positive correlation (R(S) = +0.643, p less than 0.001) was found between titers of NA and whole virus antibody (WVA), with the ratios between titers (NA titer/WVA titer) varying a 100-fold. The results suggest that the presence of NA in some cases might be related to a healthy carrier state and that a combination of low titer NA with decline of anti-gag antibodies and/or HIV antigenaemia is associated with progression to clinical disease.

Acquired Immunodeficiency Syndrome

Serological markers of primary HIV infection.

39 persons with an incidentally discovered seroconversion from HIV antibody negative (Ab-) to antibody positive (Ab+) state as measured by an enzyme-linked immunosorbent assay (ELISA) were investigated for the presence of (1) HIV antigen (Ag) and (2) immunoblotting test (IBT) Ab in serum samples collected within the year before seroconversion. 13 (33%) of the patients were HIV Ag+ at some time before seroconversion. However, the collection of samples was not done systematically and the samples from patients who had at least 1 sample collected within 3 months before seroconversion were thus compiled separately. This group consisted of 58 samples from 19 patients and among these none were HIV Ag+ earlier than 11 weeks before seroconversion, but the prevalence of HIV Ag+ samples was rising towards seroconversion and 10 patients (53%, 95% confidence limits: 29-76%) became HIV Ag+ in this 11-week period. Further, among all patients 13 (33%) were IBT Ab+ 4-50 days (median: 14 days) before seroconversion. Finally, among 18 patients with signs and symptoms consistent with an acute HIV infection 10 were HIV Ag+, as opposed to 4 HIV Ag+ patients among 21 without symptoms (p = 0.041).

Adolescent

Serological response in patients with chronic asymptomatic human immunodeficiency virus infection.

To examine a possible relationship between decreased immune function and serological parameters, such as human immunodeficiency virus (HIV) antigenaemia and the quality and quantity of whole virus antibodies and antibodies against the major core protein p24, we investigated 160 healthy HIV infected individuals (CDC classification II and III). According to the number of T-helper lymphocytes (CD4 cells) these were divided into two groups (CD4 cell counts above or below 500/microliter), which according to the lymphocyte transformation response to pokeweed mitogen (response above or below 20% of control value) were further subdivided into two groups. Both the presence of HIV antigen (p = 0.022) and the absence of p24 antibodies (p = 0.001) correlated to a decreased CD4 cell count. Lack of p24 antibodies was more frequent than was the presence of HIV antigen among persons with decreased CD4 cell count and decreased response to pokeweed mitogen, indicating that absence of p24 antibodies may be an earlier marker of immune dysfunction than the presence of HIV antigen. In persons with p24 antibodies present, a low such titer was associated with a decrease of both immune parameters. Presence of HIV antigen and absence of p24 antibodies thus seems to correlate with the severity of immune dysfunction in healthy HIV infected individuals.

Acquired Immunodeficiency Syndrome

A comparison of three methods for detection of antibodies against the major core protein p24 of human immunodeficiency virus.

The native major core protein p24 of the human immunodeficiency virus (HIV) was immunoaffinity purified by a monoclonal antibody and used to develop an indirect enzyme-linked immunosorbent assay (inELISA) for detecting p24 antibodies in human sera. Its ability to detect p24 antibodies was compared to that of the immunoblotting test (IBT) and a commercial available competition ELISA (compELISA) employing recombinant HIV core protein. In tests on 60 serum samples the overall agreement of the inELISA and the IBT was 93.3%. Fifty-two samples were p24 antibody positive in both the inELISA and the IBT and of these 24 (46.2%) were positive in the compELISA. All compELISA positive samples were derived from healthy individuals, whereas of the 28 (53.8%) compELISA negative samples 1 was from a patient with acute HIV infection, 18 from healthy individuals and 9 from ARC/AIDS patients. The compELISA was able to distinguish among healthy persons with normal or low T-helper cell count (P = 0.048), as was the inELISA when p24 antibodies were titrated (P = 0.027). The inELISA equals IBT in specificity and sensitivity, is convenient and is very suitable for titration of p24 antibodies.

AIDS-Related Complex

Myelopathy in AIDS. A clinical and electrophysiological study of 23 Danish patients.

In a cross-sectional population study of Danish patients with AIDS 16 of 23 had clinical signs of neurological disease with muscle weakness or ataxia of the lower limbs as the dominant manifestation. Tibial and median nerve conduction was mildly slowed in a few patients and 15 had widening of cerebral ventricles at CT. However, all had prolonged latency of cortical evoked response following tibial nerve stimulation mainly due to slowing through the spinal cord. The prolongation of the latency of the evoked cortical responses was most pronounced in patients with lower limb ataxia and/or paresis. It is concluded that affection of the long tracts of the spinal cord are closely associated with the human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome

Seroconversion to human immunodeficiency virus (HIV) in persons attending an STD clinic in Copenhagen.

1,182 males and 155 females attending an STD clinic from June 1984 to October 1985 were investigated for the presence of antibodies to human immunodeficiency virus (HIV). 348 (29.5%) of the males and 5 (3.2%) of the females were antibody positive (ab+). 237 of the males were initially antibody negative (ab-) and were tested more than once, and during a 16-month period 40 of these seroconverted from ab- to antibody positive. The mean follow-up period of these 40 patients was 7.1 months, and thus the seroconversion rate is estimated to be 2.4% per month. Samples from 37 of these were available for HIV antigen testing. 19 of the patients were antigen positive in the latest ab- sample and accordingly, 18 patients were antigen negative in the latest ab- sample. No difference was found between the mean follow-up periods of those with and those without HIV antigen in the latest ab- serum and the presence of HIV antigen in serum was not associated with symptoms of acute HIV infection. After 20 months of follow-up, none (0.0-8.8%, 97.5% confidence limits) of the 40 patients have developed AIDS or AIDS-related complex.

Adolescent

Immunological characterization and detection of the major core protein p24 of the human immunodeficiency virus (HIV) using monoclonal antibodies.

Eight different monoclonal antibodies (MAbs) were raised against a lysate of the HTLV-IIIb isolate of human immunodeficiency virus (HIV). All eight MAbs recognized the major core protein p24 as well as the gag precursors p39 and p55. Three different epitopes were defined by the eight MAbs when an antigen-catching ELISA was used as the test system. An antigen-catching ELISA for p24 was developed by use of two of the MAbs defining two different epitopes. This ELISA system was applied to the detection of p24 in culture supernatants from lymphocyte cultures of 13 different HIV isolates. The present p24 detecting ELISA proved useful for characterization of different isolates of HIV. Further, two MAbs from the present panel of antibodies were demonstrated to be sensitive and specific probes for the immunohistological detection of p24 protein in tissue sections of lymphoid tissue.

Animals

Human immunodeficiency virus (HIV) antibodies in patients with haemophilia and other inheritable blood clotting disorders in south west Poland (Lower Silesia region).

In order to determine the frequency of HIV antibodies among patients with haemophilia and other inheritable blood clotting disorder in the Lower Silesia region of South-West Poland, we examined a representative fraction comprising 106 patients from a cohort of 302 blood clotting disorder patients. The methods used for detecting HIV antibodies were an ELISA, the immunoblotting test ("Western blot") and an indirect immunofluorescence test. 8 patients were reactive in the ELISA, but only 2 (1.9%) patients were truly seropositive by the confirmation tests. Both patients have received imported commercial factor VIII preparation. Totally 17 patients have been treated with imported factor VIII, thus 12% (95% confidence limits: 1.5-36.5%) of these were seropositive. This figure, which is lower than figures obtained from the USA and Western Europe, is probably due to far less intensive treatment of the patients. None (95% confidence limits: 0-4.1%) of the patients solely treated with blood transfusion and locally produced preparation was HIV antibody positive. These results indicate a low prevalence of HIV infection in this region of Poland but are, on the other hand, a strong argument for an introduction of HIV antibody screening of blood donors to maintain these favourable condition.

Acquired Immunodeficiency Syndrome

Detection of antibodies to human immunodeficiency virus (HIV) in eluates from whole blood impregnated filter paper discs.

A method for elution of HIV antibodies from whole blood or serum impregnated filter paper discs was developed. The results from testing of 73 eluates in an enzyme linked immunosorbent assay and the immunoblotting test agreed with the results obtained by ordinary serum testing. Significant loss of antibody activity was not observed, neither in the eluates after storage for 1 mth at -20 degrees C nor in the filter paper discs after storage for 3 mths at +4 degrees C. This technique may be useful in facilitating sample collection and transportation, particularly in remote areas of the world.

Africa, Central